Updated Markov Model to Determine Optimal Management Strategy for Patients with Paraesophageal Hernia and Symptoms, Cameron Ulcer, or Comorbid Conditions.

BACKGROUND: The current paradigm of watchful waiting (WW) in people 65 years or older with an asymptomatic paraesophageal hernia (PEH) is based on a now 20-year-old Markov analysis. Recently, we have shown that elective laparoscopic hernia repair (ELHR) provides an increase in life-years (L-Ys) compared with WW in most healthy patients aged 40 to 90 years. However, elderly patients often have comorbid conditions and may have complications from their PEH such as Cameron lesions. The aim of this study was to determine the optimal strategy, ELHR or WW, in these patients. STUDY DESIGN: A Markov model with updated variables was used to compare L-Ys gained with ELHR vs WW in hypothetical people with any type of PEH and symptoms, Cameron lesions, and/or comorbid conditions. RESULTS: In men and women aged 40 to 90 years with PEH-related symptoms and/or Cameron lesions, ELHR led to an increase in L-Ys over WW. The presence of comorbid conditions impacted life expectancy overall, but ELHR remained the preferred approach in all but 90-year-old patients with symptoms but no Cameron lesions. CONCLUSIONS: Using a Markov model with updated values for key variables associated with management options for patients with a PEH, we showed that life expectancy was improved with ELHR in most men and women aged 40 to 90 years, particularly in the presence of symptoms and/or Cameron lesions. Comorbid conditions increase the risk for surgery, but ELHR remained the preferred strategy in the majority of symptomatic patients. This model can be used to provide individualized management guidance for patients with a PEH.

Missed Opportunities: the Timing and Frequency of Screening Colonoscopy in Patients That Develop Esophageal Adenocarcinoma.

INTRODUCTION: Screening colonoscopy (SC) is widely accepted and has been shown to decrease the rate of colorectal cancer death. Guidelines and acceptance of screening for Barrett's esophagus (BE) are less established despite the fact that esophageal adenocarcinoma (EA) remains the fastest increasing cancer in the USA. The aim of this study was to assess the timing and frequency of SC in patients ultimately found to have EA and to evaluate the presence of symptoms and risk factors that might have prompted an esophagogastroduodenoscopy (EGD) and potentially earlier diagnosis of the EA. METHODS: A retrospective chart review was performed to identify all patients who were referred to a single center with esophageal cancer between July 2016 and November 2022. Patients with any histology other than adenocarcinoma were excluded. RESULTS: There were 221 patients referred with EA. Of these, a SC had been done prior to the diagnosis of EA in 108 patients (49%): 96 men and 12 women. A total of 203 SC had been done (range 1-7 per patient), and 47% of patients had more than 1 SC. The median interval from the last SC to the diagnosis of EA was 2.9 years. At the time of SC, gastroesophageal reflux disease (GERD) symptoms or chronic acid suppression medication use was reported by 81% of patients, and 80% had an American Society of Gastrointestinal Endoscopy (ASGE) indication for a screening EGD. Only 19 patients (18%) that had a SC had an EGD at any time prior to the diagnosis of EA, and in these patients, 74% had erosive esophagitis or BE. The EA in most patients was stage III or IV and associated with lymph node metastases. CONCLUSIONS: Nearly one-half of patients ultimately diagnosed with EA had one or more SCs, and most of these patients had GERD symptoms, were using acid suppression medications or had an ASGE indication for a screening EGD. Despite this, only 18% had an EGD prior to the EA diagnosis. The addition of an EGD at the time of SC in these patients may have allowed the detection of BE or EA at an early, endoscopically curable stage and represents a missed opportunity to intervene in the natural history of this disease.

Tumor differentiation impacts response to neoadjuvant therapy and survival in patients with esophageal adenocarcinoma.

OBJECTIVE: The current staging system for esophageal adenocarcinoma only considers tumor grade in early tumors. The aim of this study was to evaluate the impact of tumor differentiation on response to neoadjuvant chemoradiotherapy and survival in patients with locally advanced esophageal adenocarcinoma. METHODS: This was a multi-institution retrospective review of all patients with esophageal cancer who underwent neoadjuvant chemoradiotherapy followed by esophagectomy from January 2010 to December 2017. Response to neoadjuvant therapy and survival was compared between patients with well- or moderately differentiated (G1/2) tumors versus poorly differentiated (G3) tumors. RESULTS: There were 550 patients, 485 men (88.2%) and 65 women. The median age was 61 years, and the tumor was G1/2 in 288 (52.4%) and G3 in 262 patients. Overall clinical stage before neoadjuvant therapy was similar between groups. Pathologic complete response (pCR) was found in 87 patients (15.8%). The frequency of pCR was similar between groups, but residual disease in the esophagus and lymph nodes was significantly more likely with G3 tumors. Median follow-up was 63 months and absolute survival, overall survival, and disease-free survival were all significantly worse in patients with G3 tumors. Further, even with pCR, patients with G3 tumors had significantly worse survival. CONCLUSIONS: This study showed that response to neoadjuvant therapy was not affected by tumor differentiation. However, poor differentiation was associated with worse survival compared with patients with G1/2 tumors, even among those with pCR. These results suggest that poor differentiation should be considered as an added risk factor for clinical staging in patients with locally advanced esophageal adenocarcinoma.

Diaphragmatic relaxing incisions for complex hiatal reconstruction: longer-term follow-up confirms safety, efficacy and rare complications.

BACKGROUND: Tension is an important factor in hernia repairs. Relaxing incisions to reduce tension are common with ventral hernia repairs, and techniques for relaxing incisions also exist for the hiatus. The aim of this study was to update our original experience with a diaphragm relaxing incision (DRI) in a larger group of patients with longer follow-up. METHODS: A retrospective chart review was performed to identify all patients who had a DRI between August 2016 and September 2021 during hiatal hernia repair. All DRI defects were repaired with permanent mesh remote from the esophagus. Objective follow-up was with chest x-ray, upper GI series (UGI) or both. RESULTS: Seventy-three patients had a total of 79 DRI (right in 63, left in 4, and bilateral in 6 patients), during a primary (n = 52) or redo (n = 21) hiatal hernia repair. Concomitant Collis gastroplasty was used in 38 patients (52%). A single intra-operative complication occurred where the right crus tore during a right DRI. At a median of 15 months, 78% of patients had objective follow-up. There was one hernia through a repaired right DRI (1.2%). No patient had evidence of diaphragm paralysis and there were no mesh infections. The 1-year hernia recurrence rate in these patients was 3.9%. CONCLUSIONS: A DRI can be done safely with minimal risk of intra- or post-operative complications. There was a low rate of herniation through the defect when repaired with permanent mesh. No patient developed a mesh infection despite concomitant Collis gastroplasty in 52% of patients, and there was no evidence of diaphragm paralysis on imaging studies. Further, the low rate of hiatal hernia recurrence suggests efficacy of a DRI to reduce crural closure tension. These excellent outcomes should encourage use of a DRI in patients with a difficult hiatus during hernia repair.

Concept mapping sociocultural aspects of cervical cancer prevention among African American women.

Introduction: For African American women in Houston, cervical cancer mortality is disproportionate to their racial and ethnic counterparts. Most notably, lack of human papillomavirus (HPV) screening and vaccination as well as late diagnosis increase cervical cancer mortality. However, cervical cancer is largely preventable. While previous research has identified a few social determinants that are specifically related to cervical cancer (e.g., education, income, neighborhood), there may be a host of additional social and cultural factors that contribute to a lack of preventative behavior. Methods: The present study used concept mapping to explore sociocultural determinants of cervical cancer prevention beliefs among young African American women. N = 15 African American women, ages 18-25, participated in a group concept mapping session focused on cervical cancer knowledge, beliefs about women's health, and how their social environment and culture play a role in their conceptualization of cervical cancer prevention. Discussion: Five overarching concepts emerged: (1) Screening, (2) Support System, (3) Cervical Cancer 101 (knowledge), (4) Fatalism, and (5) Ease of Prevention. Conclusion: The present study highlights the use of concept mapping for prevention science, particularly in exploratory studies for understanding cervical cancer screening barriers, avenues for intervention, and public health messaging. We discuss the findings and implications for public health research in cervical cancer prevention tailored for African American women.

Intraoperative valence testing to adjudicate between ventral capsule/ventral striatum and bed nucleus of the stria terminalis target selection in deep brain stimulation for obsessive-compulsive disorder.

OBJECTIVE: Deep brain stimulation (DBS) is an accepted therapy for severe, treatment-refractory obsessive-compulsive disorder (trOCD). The optimal DBS target location within the anterior limb of the internal capsule, particularly along the anterior-posterior axis, remains elusive. Empirical evidence from several studies in the past decade has suggested that the ideal target lies in the vicinity of the anterior commissure (AC), either just anterior to the AC, above the ventral striatum (VS), or just posterior to the AC, above the bed nucleus of the stria terminalis (BNST). Various methods have been utilized to optimize target selection for trOCD DBS. The authors describe their practice of planning trajectories to both the VS and BNST and adjudicating between them with awake intraoperative valence testing to individualize permanent target selection. METHODS: Eight patients with trOCD underwent awake DBS with trajectories planned for both VS and BNST targets bilaterally. The authors intraoperatively assessed the acute effects of stimulation on mood, energy, and anxiety and implanted the trajectory with the most reliable positive valence responses and least stimulation-induced side effects. The method of intraoperative target adjudication is described, and the OCD outcome at last follow-up is reported. RESULTS: The mean patient age at surgery was 41.25 ± 15.1 years, and the mean disease duration was 22.75 ± 10.2 years. The median preoperative Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score was 39 (range 34-40). Two patients had previously undergone capsulotomy, with insufficient response. Seven (44%) of 16 leads were moved to the second target based on intraoperative stimulation findings, 4 of them to avoid strong negative valence effects. Three patients had an asymmetric implant (1 lead in each target). All 8 patients (100%) met full response criteria, and the mean Y-BOCS score reduction across the full cohort was 51.2% ± 12.8%. CONCLUSIONS: Planning and intraoperatively testing trajectories flanking the AC-superjacent to the VS anteriorly and to the BNST posteriorly-allowed identification of positive valence responses and acute adverse effects. Awake testing helped to select between possible trajectories and identify individually optimized targets in DBS for trOCD.

POEM: clinical outcomes beyond 5 years.

BACKGROUND: The short-term success of peroral endoscopic myotomy (POEM) is well documented but the durability of the operation is questioned. The aim of this study was to evaluate the clinical outcomes of the POEM procedure for esophageal motility disorders in a large cohort in which all patients had at least 5 years of follow-up. METHODS: All patients from a single center who underwent a POEM between October 2010 and September 2014 were followed for long-term clinical outcomes. Postoperative Eckardt symptom scores of short term and ≥ 5 years were collected through phone interview. Clinical success was defined as an Eckardt score < 3. Overall success was defined as Eckardt score < 3 and freedom from additional interventions. RESULTS: Of 138 patients, 100 patients were available for follow-up (mean age 56, 52% male). The indication for operation was achalasia in 94. The mean follow-up duration was 75 months (range: 60-106 months). Dysphagia was improved in 91% of patients. Long-term overall success was achieved in 79% of patients (80% of achalasia patients, 67% of DES patients). Preoperative mean Eckardt score was 6. At 6 months, it was 1, and at 75 months, it was 2 (p = 0.204). Five-year freedom from intervention was 96%. Overall, 7 patients had additional treatments: 1 balloon dilation (35 mm), 4 laparoscopic Heller myotomy, and 2 redo POEM at a mean of 51 months post-POEM. Ninety-three percent expressed complete satisfaction with POEM. CONCLUSION: A multitude of studies has shown the early benefits of POEM. Here, we show that nearly 80% of patients report clinical success with no significant decrement in symptom scores between their short- and long-term follow-up. Clearly POEM is an effective option for achalasia with durable long-term treatment efficacy.

Baseline cocaine demand predicts contingency management treatment outcomes for cocaine-use disorder.

Cocaine use disorder (CUD) is a significant public health issue. Behavioral interventions such as contingency management (CM) have been demonstrated to be highly effective in promoting cocaine abstinence. However, identifying individual characteristics associated with cocaine relapse may help improve treatment outcomes. Cocaine demand is a behavioral economic measure that shares a scientific foundation with CM. In the current study, we assessed baseline cocaine demand using a hypothetical cocaine purchasing task. Participants (N = 58) consisted of treatment-seeking individuals with CUD. All participants received 1 month of CM treatment for cocaine abstinence, and treatment responders were defined as presenting 6 consecutive cocaine negative urine samples from thrice weekly clinic visits. Demand data were well described by the exponentiated demand model. Indices of demand (intensity of demand [Q0], elasticity [α]) were significantly associated with recent (last 30 days) cocaine use. Importantly, linear regression revealed that CM treatment nonresponders presented significantly higher Q0 (p = .025). Subsequent quantile regression analyses examining the relationship between CM treatment response and Q0 revealed statistically reliable effects of being a nonresponder across 3 of the lower percentiles (i.e., 15, 25, and 30). Overall, these findings provide further support for the utility of exponentiated demand model. To our knowledge, this is the first study to demonstrate an association between baseline demand and contingency management response and systematically extend the findings of prior demand research to a novel drug class, cocaine. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Calibration and validation of a microporous polyethylene passive sampler for quantitative estimation of illicit drug and pharmaceutical and personal care product (PPCP) concentrations in wastewater influent.

Wastewater-based epidemiology (WBE), the per capita normalised measurement of drugs, chemicals or metabolites in wastewater influent, relies on sampling and quantitative analysis to evaluate temporal and spatial trends of chemical consumption. Continuous, high-resolution, flow proportional composite sampling is optimal for accurate representations of chemical mass loads, but is rarely implemented, with conventional autosamplers providing relatively low frequency time or volume proportional samples. However, due to equipment or resource constraints at many wastewater treatment plants (WWTPs), even this may not be feasible. Passive sampling may provide an alternative sampling strategy. To investigate this, samplers comprising hollow, cylindrical Microporous Polyethylene Tubes (MPTs) containing polymeric sorbent phases of Strata-X and Strata-X in agarose were simultaneously deployed in a municipal WWTP influent stream. Samplers were extracted, analysed and evaluated for a range of illicit drugs and pharmaceuticals and personal care products (PPCPs) after 4, 7, 15, 21, and 29 day deployments. The MPT samplers were calibrated against 24-hour time proportional composite grab samples that were collected in parallel. Diffusion through the MPT governed uptake, reducing or eliminating the influence of external flow rates that may fluctuate unpredictably in a WWTP environment. Calibration data for six illicit drugs and fourteen PPCPs, including methamphetamine, benzoylecgonine, MDMA, codeine and carbamazepine, demonstrated linear accumulation in the samplers (R2 ≥ 0.84). Derived sampling rates for these analytes ranged from 0.25 to 17 mL d-1 for ibuprofen and verapamil, respectively. A validation study using this sampling rate data showed the MPT could effectively quantify concentrations (≥0.1 ng mL-1) of a range of amphetamine-type stimulants, opioids and metabolites as well as nicotine, accounting for 95% of the variance in parallel composite grab sample concentrations of these compounds. The MPT sampler shows promise for providing essential monitoring data for WBE, informing future intervention and research strategies.

Clonal hematopoiesis as determined by the HUMARA assay is a marker for acquired mutations in epigenetic regulators in older women.

Recent large cohort studies revealed that healthy older individuals harbor somatic mutations that increase their risk for hematologic malignancy and all-cause cardiovascular deaths. The majority of these mutations are in chromatin and epigenetic regulatory genes (CERGs). CERGs play a key role in regulation of DNA methylation (DNMT3A and TET2) and histone function (ASXL1) and in clonal proliferation of hematopoietic stem cells. We hypothesize that older women manifesting clonal hematopoiesis, defined here as a functional phenomenon in which a hematopoietic stem cell has acquired a survival and proliferative advantage, harbor a higher frequency of somatic mutations in CERGs. The human androgen receptor gene (HUMARA) assay was used in our study to detect the presence of nonrandom X inactivation in women, a marker for clonal hematopoiesis. In our pilot study, we tested 127 blood samples from women ≥65 years old without a history of invasive cancer or hematologic malignancies. Applying stringent qualitative criteria, we found that 26% displayed clonal hematopoiesis; 52.8% displayed polyclonal hematopoiesis; and 21.3% had indeterminate patterns (too close to call by qualitative assessment). Using Illumina MiSeq next-generation sequencing, we identified somatic mutations in CERGs in 15.2% of subjects displaying clonal hematopoiesis (three ASXL1 and two DNMT3A mutations with an average variant allele frequency of 15.7%, range: 6.3%-23.3%). In a more limited sequencing analysis, we evaluated the frequency of ASXL1 mutations by Sanger sequencing and found mutations in 9.7% of the clonal samples and 0% of the polyclonal samples. By comparing several recent studies (with some caveats as described), we determined the fold enrichment of detecting CERG mutations by using the HUMARA assay as a functional screen for clonal hematopoiesis. We conclude that a functional assay of clonal hematopoiesis is enriching for older women with somatic mutations in CERGs, particularly for ASXL1 and TET2 mutations and less so for DNMT3A mutations.

Etiology of unilateral neural hearing loss in children.

OBJECTIVE: Unilateral sensorineural hearing loss (SNHL) can be caused by a variety of lesions of the inner ear and central nervous system. An inner hair cell or neural site of pathology must be suspected when otoacoustic emissions (OAEs) are present, and inconsistent with audiologic data. We reviewed unilateral neural hearing loss (UNHL) in children, to better understand its etiology, clinical and audiologic features. DESIGN: Retrospective series. SETTING: Tertiary pediatric center. METHODS: From a database of 480 children with unilateral SNHL, 148 had OAE data. Patients with a neural pattern (present OAEs in the affected ear) were reviewed. OUTCOME MEASURES: Clinical course, audiologic data, imaging findings. RESULTS: Of 148 patients with OAE data, 11 (7.4%) had the unilateral neural phenotype. Most had stable, severe-to-profound loss in the affected ear. MRI determined an etiology in all 10 patients who received it. Absent cochlear nerves were remarkably common, being found in eight patients (73%). Tumors, previously unsuspected, were identified in the other two patients who received MRI. CONCLUSIONS: Cochlear nerve aplasia appears by far the most common cause of UNHL in children. As in adults, mass lesions must also be considered in children with unilateral SNHL with a neural pattern. As both lesions elude diagnosis on CT, MRI is the better modality for evaluating this condition.

Microsurgical access for cell injection into the mammalian cochlea.

The potential use of stem cells to repair hearing loss requires surgical access to the cochlea. Here we describe a microsurgical technique for cell injection into the mouse cochlea. Green fluorescent cells (ZsGreen-MCF10A cells) were successfully injected via a lateral wall cochleostomy into the scala media, scala tympani and scala vestibuli compartments of the cochlea. The effect of surgery on auditory function was investigated with auditory brainstem responses (ABR) to click and tone stimuli. A computerised signal-to-noise ratio detection method was developed to measure ABR thresholds in conjunction with visual inspection. Signal-to-noise ratio detection showed ABR thresholds in control mice were similar for click (33+/-7 dB) and tone stimuli (33+/-6 dB), in agreement with visual inspection (click 39+/-7 dB, tone 35+/-6 dB). The mean ABR threshold for combined click and tone stimuli was 15-45 dB greater after surgery with minimum hearing loss achieved with a small sized cochleostomy (< or =0.4mm) and by sibling matching to control mice (control 33+/-4 dB, surgery 48+/-3 dB). The microsurgical technique will provide a basis for future studies on the use of stem cells in the treatment of hearing loss.

Inflammation of rat dorsal root ganglia below a mid-thoracic spinal transection.

Macrophages and T-lymphocytes invade the spinal cord in and around a lesion and spinal microglia are converted into macrophages. After spinal transection at T8 in rats, T-lymphocyte and major histocompatibility complex II+ (MHC II+) macrophage numbers were increased within dorsal root ganglia (DRGs) below the lesion. Inflammation was greater in DRGs closer to the site of transection. After 8 weeks, MHC II+cell density had fallen by 30% but T-lymphocyte numbers were undiminished. In lumbosacral DRGs, inflammation preceded inflammation within the spinal cord. The responses in distant DRGs are hard to reconcile with the limited damage to sensory neurons produced by the lesion. Inflammation of DRGs after spinal injury may contribute to hyper-reflexia and pain.