[Achalasia cardiae causing megaesophagus: "From the beginnings to the resolution"]. / Megaoesophagust okozó achalasia cardiae: "a kezdetektol a megoldásig".

Achalasia cardiae miatt az elso oesophago-cardia myotomiát több mint száz évvel ezelott Ernst Heller német sebész végezte. Az achalasiás betegek a mai napig ettol a beavatkozástól várják panaszaik megszunését. Az achalasia napjainkban is chronikus, progresszív betegség, aminek oki kezelését nem ismerjük, a gyógyítására, a panaszok enyhítésére gyógyszeres (calcium csatorna blokkolók stb.), endoscopos (botulinum toxin inj., ballonos tágítás, per oralis endoscopos myotomiát [POEM]) és sebészi (laparoscopos, thoracoscopos myotomia) kezeléseket váltakozó sikerrel alkalmazunk.A betegség progresszivitása miatt a betegek 5%-ánál a nyelésképtelenségig fokozódó dysphagia, megaoesophagus alakul ki, megoldására mutéti beavatkozás válik szükségessé. A muködésképtelen nyelocso eltávolítása és pótlása kiterjedt, nem elhanyagolható morbiditással és mortalitással járó beavatkozás. Közleményünkben egy 45 éves nobeteg kórtörténetét, az általunk alkalmazott mutéti beavatkozást ismertetjük. A beteg a mutét óta panaszmentes.

Efficacy and safety of laparoscopic Heller's myotomy versus pneumatic dilatation for achalasia: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVES: Achalasia has several treatment modalities. We aim to compare the efficacy and safety of laparoscopic Heller myotomy (LHM) with those of pneumatic dilatation (PD) in adult patients suffering from achalasia. METHODS: We searched Cochrane CENTRAL, PubMed, Web of Science, SCOPUS and Embase for related clinical trials about patients suffering from achalasia. The quality appraisal and assessment of risk of bias were conducted with GRADE and Cochrane's risk of bias tool, respectively. Homogeneous and heterogeneous data was analyzed under fixed and random-effects models, respectively. RESULTS: The pooled analysis of 10 studies showed that PD was associated with a higher rate of remission at three months, one year, three years and five years (RR = 1.25 [1.09, 1.42] (p = 0.001); RR = 1.13 [1.05, 1.20] (p = 0.0004); RR = 1.48 [1.19, 1.82] (p = 0.0003); RR = 1.49 [1.18, 1.89] (p = 0.001)), respectively. LHM was associated with lower number of cases suffering from adverse events, dysphagia and relapses (RR = 0.50 [0.25, 0.98] (p = 0.04); RR = 0.33 [0.16, 0.71] (p = 0.004); RR = 0.38 [0.15, 0.97] (p = 0.04)), respectively. There is no significant difference between both groups regarding the lower esophageal pressure, perforations, remission rate at two years, Eckardt score after one year and reflux. CONCLUSION: PD had higher remission rates than LHM at three months, one year and three years, but not at two years or five years. More research is needed to determine whether PD has a significant advantage over LHM in terms of long-term remission rates.

Effects of Anterior Fundoplication on Postoperative Dysphagia and Reflux After Laparoscopic Esophagocardiomyotomy for Pediatric Achalasia.

Introduction: Achalasia among children often fails endoscopic management (e.g., dilation, botulinum toxin). Laparoscopic esophagocardiomyotomy (L-ECM) is a standard intervention to relieve obstruction but can induce gastroesophageal reflux (GER). Concurrent anterior fundoplication (A-fundo) has been evaluated in randomized trials among adults, demonstrating mixed results on controlling postoperative GER without exacerbating dysphagia. Furthermore, evidence for the best approach among children remains sparse. We hypothesized that, among children undergoing L-ECM without mucosal violation, routine A-fundo would not improve postoperative GER control while exacerbating dysphagia. Materials and Methods: Observational data of 47 consecutive achalasia patients ≤18 years who received L-ECM (2002-2023) at a single academic institution were collected. Patient records were culled for demographics, achalasia characteristics, and outcomes. Two L-ECM groups were identified: with or without A-fundo. Patients were screened for postoperative dysphagia (additional procedures) and GER (new antireflux medications). Univariate independence testing was conducted to identify statistically significant variables. Results: Among 47 patients undergoing L-ECM, 28 (59.6%) received concurrent A-fundo. Compared with patients undergoing L-ECM alone, patients with L-ECM/A-fundo had significantly longer hospital stays (P < .01) without statistically different rates of postoperative dysphagia (P = .81) or GER (P = .51). Five children (10.6%) experienced mucosal injury with L-ECM: 4 recognized intraoperatively received A-Fundo without subsequent leak; 1 mucosal injury was missed and did not receive A-Fundo, which subsequently leaked. Conclusion: In this largest observation of pediatric achalasia patients, A-fundo appeared clinically insignificant when determining contributors to control GER or exacerbate postoperative dysphagia. A-fundo should not be routinely adopted in children having L-ECM for achalasia without further multicenter analysis but appears beneficial in cases having inadvertent mucosal violation.

Prediction, prevention and management of gastroesophageal reflux after per-oral endoscopic myotomy: An update.

Achalasia cardia, the most prevalent primary esophageal motility disorder, is predominantly characterized by symptoms of dysphagia and regurgitation. The principal therapeutic approaches for achalasia encompass pneumatic dilatation (PD), Heller's myotomy, and the more recent per-oral endoscopic myotomy (POEM). POEM has been substantiated as a safe and efficacious modality for the management of achalasia. Although POEM demonstrates superior efficacy compared to PD and an efficacy parallel to Heller's myotomy, the incidence of gastroesophageal reflux disease (GERD) following POEM is notably higher than with the aforementioned techniques. While symptomatic reflux post-POEM is relatively infrequent, the significant occurrence of erosive esophagitis and heightened esophageal acid exposure necessitates vigilant monitoring to preclude long-term GERD-related complications. Contemporary advancements in the field have enhanced our comprehension of the risk factors, diagnostic methodologies, preventative strategies, and therapeutic management of GERD subsequent to POEM. This review focuses on the limitations inherent in the 24-h pH study for evaluating post-POEM reflux, potential modifications in the POEM technique to mitigate GERD risk, and the strategies for managing reflux following POEM.

Abnormal performance of peroral endoscopic myotomy (POEM): a case misdiagnosed as achalasia of cardia.

BACKGROUND: Pseudoachalasia is a rare disease that behaves similarly to achalasia (AC), making it sometimes difficult to differentiate. CASE PRESENTATION: We report a case of 49-year-old male with adenocarcinoma of the gastroesophageal junction misdiagnosed as achalasia. No obvious abnormalities were found in his initial examinations including upper digestive endoscopy, upper gastrointestinal imaging and chest computed tomography (CT). During the subsequent introduced-peroral endoscopic myotomy (POEM), it was found that the mucosal layer and the muscular layer had severe adhesion, which did not receive much attention, delayed the clear diagnosis and effect treatment, and ultimately led to a poor prognosis for the patient. CONCLUSIONS: This case suggests that when patients with AC found mucosal and muscular adhesions during POEM surgery, the possibility should be considered that the lesion may be caused by a malignant lesion.

Oral and Pharyngeal Dysphagia in Adults.

Patients with oral and pharyngeal dysphagia have difficulty forming a cohesive bolus and/or transferring food from the mouth into the pharynx and esophagus to initiate the involuntary swallowing process. This may be accompanied by nasopharyngeal regurgitation, aspiration, and a sensation of residual food remaining in the pharynx. Abnormalities affecting the upper esophageal sphincter, pharynx, larynx, or tongue, in isolation or combination, result in oropharyngeal dysphagia affecting either or both transit and airway protection. These issues can be addressed with a combination of management of the underlying systemic disease, with surgical intervention or with swallow therapy.

Sudden-Onset Back Pain and Intermittent Dyspnea While Eating: A Case of Pediatric Achalasia.

A 14-year-old girl with a history of asthma was hospitalized because of sudden-onset back pain around her thoracic region that spread to her chest and abdomen. She had been experiencing dysphagia and breathing difficulties for two years, especially after overeating, which often resulted in vomiting undigested food. CT imaging revealed a severely dilated esophagus narrowing at the gastroesophageal junction, suggestive of type 1 achalasia. Further testing confirmed the diagnosis, with an esophageal manometry showing a lack of esophageal contractions and sphincter relaxation. She then underwent a laparoscopic Heller myotomy with relief to her symptoms. This case underscores the rarity of pediatric-onset achalasia with significant esophageal dilation and secondary airway compression, presenting with unusual musculoskeletal and respiratory symptoms. Timely diagnosis and treatment are crucial to prevent worsening and complications.

The evolution of the treatment of esophageal achalasia. Chronicle of a 35-year journey.

Over the last few decades, significant improvement has been made in both the evaluation and treatment of esophageal achalasia. The Chicago classification, today in version 4.0, is now the standard for diagnosis of achalasia, providing a classification into 3 subtypes with important therapeutic and prognostic implications. Therapy, which was at first mostly limited to pneumatic dilatation, today includes minimally invasive surgery and peroral endoscopic myotomy, allowing for a more tailored approach to patients and better treatment of recurrent symptoms. This review chronicles my personal experience with achalasia over the last 35 years, describing the progress made in the treatment of patients with achalasia.

Quantification of interstitial cells of Cajal and fibrosis during gastric per-oral endoscopic myotomy and its association with clinical outcomes.

Background and study aims Alterations to interstitial cells of Cajal (ICC) and collagen fibrosis have been implicated in the pathogenesis of gastroparesis. We aimed to evaluate the feasibility and safety of pyloric muscle sampling during gastric peroral endoscopic myotomy (G-POEM) and the association between pyloric ICC density and degree of fibrosis with clinical outcomes. Patients and methods This was a single-center prospective study of gastroparetic patients who underwent G-POEM and intraprocedural pyloric muscle biopsies between January 2022 and April 2023. ICC count was estimated using CD117 stain and trichome for collagen fibrosis. Clinical response to G-POEM was defined as an improvement of ≥ 1 point on the Gastroparesis Cardinal Symptom Index. Results Fifty-six patients (median age 60 years, 71.4% women) underwent G-POEM (100% technical success; 71.4% clinical response). ICC depletion (< 10/high-power field) and fibrosis were encountered in 70.4% and 75% of the cases, respectively. There was no difference in mean ICC count between G-POEM responders vs. non-responders (7±3.6 vs. 7.7±3.3; P = 0.9). There was no association between ICC density or degree of fibrosis with the etiology of gastroparesis, duration of symptoms, gastric emptying rate, or pyloric impedance planimetry. Patients who did not respond to G-POEM had a significantly higher degree of moderate/severe fibrosis when compared with those who responded (81.3% vs. 25%; P = 0.0002). Conclusions Pyloric muscle biopsies during G-POEM was feasible and safe. ICC depletion and pyloric muscle fibrosis are common in gastroparetic patients. The degree of fibrosis may be related to pyloric dysfunction and clinical response to G-POEM. Additional studies are needed to confirm these results.

Safety and efficacy of EsoFLIP dilation in patients with esophageal dysmotility: a systematic review.

Esophageal manometry is utilized for the evaluation and classification of esophageal motility disorders. EndoFlip has been introduced as an adjunctive test to evaluate esophagogastric junction (EGJ) distensibility. Treatment options for achalasia and EGJ outflow obstruction (EGJOO) include pneumatic dilation, myotomy, and botulinum toxin. Recently, a therapeutic 30 mm hydrostatic balloon dilator (EsoFLIP, Medtronic, Minneapolis, MN, USA) has been introduced, which uses impedance planimetry technology like EndoFlip. We performed a systematic review to evaluate the safety and efficacy of EsoFLIP in the management of esophageal motility disorders. A systematic literature search was performed with Medline, Embase, Web of science, and Cochrane library databases from inception to November 2022 to identify studies utilizing EsoFLIP for management of esophageal motility disorders. Our primary outcome was clinical success, and secondary outcomes were adverse events. Eight observational studies including 222 patients met inclusion criteria. Diagnoses included achalasia (158), EGJOO (48), post-reflux surgery dysphagia (8), and achalasia-like disorder (8). All studies used 30 mm maximum balloon dilation except one which used 25 mm. The clinical success rate was 68.7%. Follow-up duration ranged from 1 week to a mean of 5.7 months. Perforation or tear occurred in four patients. EsoFLIP is a new therapeutic option for the management of achalasia and EGJOO and appears to be effective and safe. Future comparative studies with other therapeutic modalities are needed to understand its role in the management of esophageal motility disorders.

Incidence and risk factors of reflux esophagitis after peroral endoscopic myotomy.

BACKGROUND: Peroral endoscopic myotomy (POEM) is an effective and safe treatment for achalasia, but often leads to posttreatment gastroesophageal reflux disease. The aim of this study was to examine the incidence and severity of reflux esophagitis after POEM and to identify associated predictive factors. METHODS: Patients who underwent POEM between August 2011 and December 2022 were included. Multivariate logistic regression was used to assess predictive factors for reflux esophagitis after POEM. KEY RESULTS: In total, 252 patients were included; of which, 46% were female and age ranged between 18 and 87 years. Reflux esophagitis within 1 year after POEM was observed in 131 patients (52%), which was severe in 29 patients (LA grade C/D, 12%). Length of full-thickness myotomy (cm; OR 1.11, 95% CI 1.02-1.21), Eckardt scores before POEM (OR 0.84, 95% CI 0.74-0.96), previous pneumatic dilation (OR 0.51, 95% CI 0.29-0.91), and previous laparoscopic Heller myotomy (LHM; OR 0.44, 95% CI 0.23-0.86) were associated with reflux esophagitis after POEM. Alcohol use (none vs > 7 units per week; OR 3.51, 95% CI 1.35-9.11) and overweight (BMI ≥25 kg/m2; OR 2.67, 95% CI 1.17-6.09) were positive predictive factors and previous LHM (OR 0.13, 95% CI 0.02-0.95) was a negative predictive factor for severe reflux esophagitis after POEM (LA grade C/D). CONCLUSION: About half of the patients develop reflux esophagitis after POEM and 12% is graded as severe. Recognizing predictive factors of reflux esophagitis after POEM treatment leads to better patient selection before POEM and provides an opportunity to take preventive measures or start preemptive treatment.

End-Stage Achalasia With Megaesophagus Refractory to Two Heller Myotomies.

Achalasia is a motility disorder of the esophagus in which the lower esophageal sphincter fails to relax. Megaesophagus is a rare complication of achalasia characterized by severe dilatation of the esophagus, often indicative of end-stage achalasia. Typical presenting symptoms include dysphagia, nausea, vomiting, weight loss, and chest pain. The majority of patients with achalasia typically have excellent outcomes after surgical intervention with Heller myotomy. We discuss an interesting case of unsuccessful surgical intervention and hypothesize the reason for its failure in our patient.

Retrograde tubing as a rescue treatment for megaoesophagus: a case report.

Familial dysautonomia (FD) is a genetic disease of the autonomous and sensory nervous systems. Severe gastro-oesophageal reflux is common and one of the major complications. Some patients with FD develop megaoesophagus. Oesophageal malfunction, accompanied by oesophageal food and secretion retention, results in recurrent aspiration and other severe respiratory complications. Through a traditional case report, we wish to show how reverse tubing of the oesophagus can lead to significant symptomatic improvement in these patients. Moreover, this technique can serve as an alternative treatment for other oesophageal motility disorders.

Role of modified Glasgow Prognostic Score in patients with achalasia who underwent laparoscopic Heller-myotomy with Dor-fundoplication.

BACKGROUND: Systemic inflammatory response is significant prognostic indicator in patients with various diseases. The relationship between prognostic scoring systems based on the modified Glasgow Prognostic Score (mGPS) and achalasia in patients treated with laparoscopic Heller­myotomy with Dor­fundoplication (LHD) remains uninvestigated. This study aimed to examine the role of mGPS in patients with achalasia. METHODS: 457 patients with achalasia who underwent LHD as the primary surgery between September 2005 and December 2020 were included. We divided patients into the mGPS 0 and mGPS 1 or 2 groups and compared the patients' background, pathophysiology, symptoms, surgical outcomes, and postoperative course. RESULTS: mGPS was 0 in 379 patients and 1 or 2 in 78 patients. Preoperative vomiting and pneumonia were more common in patients with mGPS of 1 or 2. There were no differences in surgical outcomes. Postoperative upper gastrointestinal endoscopy revealed that severe esophagitis was more frequently observed in patients with mGPS of 1 or 2 (P < 0.01). The clinical success was 91% and 99% in the mGPS 0 and mGPS 1 or 2 groups, respectively (P < 0.01). CONCLUSIONS: Although severe reflux esophagitis was more common in patients with achalasia with a high mGPS, good clinical success was obtained regardless of the preoperative mGPS.

Perioperative outcomes of the surgical management of achalasia in two tertiary Cameroonian hospitals: a cohort study.

INTRODUCTION: Achalasia is a rare esophageal disease with potentially lethal complications. Knowledge of the outcomes of the different surgical treatment modalities for achalasia by Heller's cardiomyotomy (HCM) helps to choose the safest and most effective option. However, data on the management of achalsia using a Heller myotomy is limited in Africa. Thus, our aim was to determine the perioperative morbidity, mortality and short-term functional outcomes of HCM in Cameroon. METHODOLOGY: We conducted a cohort study throughout a 10-year chart review of patients who underwent HCM for achalasia and were followed up postoperatively for at least three months at two tertiary health centers in Cameroon. We analyzed demographic data, preoperative clinical and imaging data, treatment details, and outcomes at three to twelve months after HCM using the Eckardt score. RESULTS: We enrolled 29 patients with achalasia having a mean age of 24 ± 16 years and predominantly females (M/F of 1/3.8). The mean symptom duration was 51 ± 20 months. In 80% of cases, the diagnosis was made through a conventional x-ray contrast imaging or "barium swallow test" (93%) and/or an upper gastrointestinal endoscopy (86%). The gold standard diagnostic method via esophageal manometry was unavailable. Preoperatievly, all patients had symptoms suggestive of an active achalasia. HCM was performed via laparotomy in 75% as opposed to 25% laparoscopic HCM procedures. Dor's anterior partial fundoplication was the main anti-reflux procedure performed (59%). Mucosal perforations were the only intraoperative complications in eight patients (2 during laparoscopy vs. 6 during laparotomy; p > 0.5) and were managed successfully by simple sutures. Postoperative complications were non-severe and occurred in 10% of patients all operated via laparotomy. The mean postoperative length of hospital stay was 7 ± 3 days for laparotomy vs. 5 ± 2 days for laparoscopy; p > 0.5. The perioperative mortality rate was nil. Overall, the short-term postoperative functional outcome was rated excellent; average Eckardt score of 1.5 ± 0.5 (vs. preoperative Eckardt Score of 9 ± 1; p < 0.0001). CONCLUSION: Achalasia is diagnosed late in this resource-limited setting. HCM yields satisfactory outcomes, especially via laparoscopic management. An improvement in diagnostic esophageal manometry and mini-invasive surgical infrastructure and the required surgical training/skills are needed for optimal achalasia care.

Global trends in incidence and prevalence of achalasia, 1925-2021: A systematic review and meta-analysis.

BACKGROUND: Achalasia poses a significant socioeconomic burden, yet global trends remain undocumented. This study aims to describe the worldwide trends in the incidence and prevalence of achalasia from 1925 to 2021 and explore their correlation with various factors through a comprehensive systematic review. METHODS: We searched the PubMed/MEDLINE, Embase, and Cochrane databases from inception to 30 June 2023, to identify studies reporting the incidence or prevalence of achalasia in the general population. This study utilized pooled estimates with 95% confidence intervals (CI) to estimate the incidence and prevalence of achalasia, and conducted various subgroup analyses. RESULTS: A total of 26 eligible studies covering approximately 269 million participants and 20,873 patients from 14 countries across five continents were included. Global pooled incidence and prevalence of achalasia were estimated to be 0.78 cases per 100,000 person-years (95% CI, 0.64-0.93; number of studies, 26; sample population, 269,315,171) and 10.82 cases per 100,000 person-years (95% CI, 8.15-13.48; number of studies, 14; sample population, 192,176,076), respectively. The incidence of achalasia was higher in Oceania (than Asia and Africa) and in adults (than children) after the introduction of the Chicago classification. Prevalence followed a similar pattern. The pooled incidence of achalasia showed an overall upward trend from 1925 to 2021 (1925-1999; 0.40 [0.32-0.49] vs. 2018-2021; 1.64 [1.33-1.95] cases per 100,000 person-years). CONCLUSIONS: The incidence and prevalence of achalasia have notably increased, particularly with advancements in diagnosis, and show significant variation worldwide, despite the large heterogeneity within the sample population. Further studies are necessary to accurately assess the global incidence and prevalence of achalasia.

Risk Factors Associated with Unsuccessful High-Resolution Manometry.

High-resolution manometry (HRM) is used to evaluate the esophageal motor function. Unfortunately, there are times when testing cannot be performed accurately. Our study aimed to quantify the occurrence of failed HRM and identify the associated risk factors. HRM tests were retrospectively collected between September 2021 and August 2022. HRM reports that could not be interpreted based on standard HRM protocol as per Chicago guidelines were classified as failed tests. Information reviewed included testing indications, patient demographics, previous medical/symptom history, and follow-up testing for failed HRM. We then compared patients with successful vs. unsuccessful HRM based on our pre-specified factors. 152 HRM tests were performed, of which 28 tests (18%) were unsuccessful. Factors associated with failed manometry included a history of nausea/vomiting, dyspepsia, and achalasia. Patients who were unable to tolerate the probe during testing were more likely to have a history of dyspepsia (OR 20.3, p = < 0.001) and/or nausea/vomiting (OR 13.8, p = < 0.001). A history of achalasia was found to have an odds ratio of 13.2 when examining failure because of curling of the manometry catheter (p = 0.012). All seven patients who had repeat HRM with endoscopic placement were successful in obtaining diagnostic information. There are two groups that have risk factors for unsuccessful HRM testing. A history of nausea/vomiting and dyspepsia symptoms were associated with being unable to tolerate the manometry probe. The second group comprises patients with a history of achalasia in whom probe curling is more common. Future research targeting these risk factors may minimize diagnostic and treatment delays.

Long-term efficacy of peroral endoscopic myotomy for achalasia under different criteria.

BACKGROUND: Peroral endoscopic myotomy (POEM) has emerged as a widely accepted treatment for achalasia, with limited studies for over 2 years. Additionally, traditional measurements of achalasia after POEM have deficiencies. The study aimed to analyze the long-term outcomes of POEM under different criteria. METHODS: Patients with achalasia who received POEM between November 2012 and March 2021 were recruited. Patients and characteristics were shown, and risk factors related to two novel definitions of recurrence, symptomatic reflux, and reflux esophagitis were analyzed. RESULTS: Three hundred and twenty-one patients were included. At a median follow-up of 52 months, twenty-three failures happened (7.17%) under the modified criterion, and forty-seven failures occurred (14.64%) under the normal standard. Hospitalization (P = 0.027) and esophageal myotomy length (P = 0.039) were significantly associated with long-term efficacy under the modified and normal criteria, respectively. Fifty-two patients (16.20%) reported reflux symptoms and endoscopy performed in 88 patients revealed reflux esophagitis in 22 cases (25.00%). There were no predictors in the analysis of symptomatic reflux and gender (P = 0.010), LESP (P = 0.013), IRP (P = 0.015), and the esophageal myotomy length (P = 0.032) were statistically related to reflux esophagitis. CONCLUSION: POEM is an extremely safe and effective treatment for achalasia with long-term follow-up. Shorter hospitalization and shorter esophageal myotomy length may decrease the incidence of recurrence under the modified and normal criteria, respectively. Long-term outcomes of POEM are unpredictable. No risk factors were related to symptomatic reflux, and male patients with low preoperative LESP and IRP needed relatively shorter esophageal myotomy to prevent reflux esophagitis.

A case of severe Mycobacterium thermoresistibile pneumonia.

Mycobacterium thermoresistibile is a thermotolerant nontuberculous mycobacterium which can rarely result in human infection. Although immunosuppression has been identified as a risk factor for infection, it is possible that mycobacterial laboratories may have previously under-recognized M. thermoresistibile as standard mycobacterial incubation temperatures are suboptimal for culture of this organism. Here, we present a case of severe M. thermoresistibile pneumonia associated with achalasia requiring life support in the intensive care unit. We speculated that the interplay between specific host and environmental risk factors contributed to acquisition of infection. Infection with this fastidious organism required prolonged treatment with multiple antimicrobials and adjunctive therapeutic drug monitoring which led to clinical cure despite residual lung injury. We also reviewed literature documenting cases of human infection with M. thermoresistibile. The diagnosis of M. thermoresistibile requires a high degree of clinical suspicion considering its association with immunosuppressive conditions, postulated environmental inoculation and eponymous culture growth characteristics.