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Topic:Gastrointestinal Diseases

Gastrointestinal diseases in horses encompass a range of disorders affecting the digestive tract, from the mouth to the intestines. These conditions can include colic, gastric ulcers, enteritis, and colitis, among others. The gastrointestinal system in horses is complex and sensitive, making it susceptible to various disruptions. Factors such as diet, management practices, and environmental stressors can influence the onset and progression of these diseases. Understanding the pathophysiology, diagnosis, and treatment options for gastrointestinal diseases is essential for maintaining equine health and welfare. This page aggregates peer-reviewed research studies and scholarly articles that explore the causes, clinical presentations, and management strategies for gastrointestinal diseases in horses.
CD3+ T-Lymphocytic Coeliac-Mesenteric Ganglioneuritis Associated with Colonic Torsion and Inflammatory Bowel Disease in an Arabian Broodmare.
Journal of comparative pathology    April 9, 2022   Volume 194 1-6 doi: 10.1016/j.jcpa.2022.03.002
Asakawa MG, Jamieson CA, David F, Johnson JP, Mehmood W, Oikawa MA.A 5-year-old Arabian broodmare with acute colic was diagnosed with lymphocytic ganglioneuritis of the coeliac-mesenteric ganglia and lymphocytic‒plasmacytic enterocolitis resembling inflammatory bowel disease. No significant pathogens were identified by aerobic culture or histopathological examination. The ganglia were multifocally infiltrated with small lymphocytes that were immunopositive for CD3 and negative for CD20 and CD79a antigens, indicating CD3+ T-lymphocyte-mediated coeliac-mesenteric ganglioneuritis. The findings suggest immune-mediated inflammatory bowel disease resulting in dis...
Changes in the gut microbiome and colic in horses: Are they causes or consequences?
Open veterinary journal    April 6, 2022   Volume 12, Issue 2 242-249 doi: 10.5455/OVJ.2022.v12.i2.12
Lara F, Castro R, Thomson P.The gut microbiome is a compound for millions of microorganisms that coexist in an organized way and contribute to the fermentation of different types of indigestible fibers by the small intestine. Some techniques, such as the massive sequencing of the 16S ribosomal RNA gene, have made it possible to obtain information about the abundance and functionality of the microorganisms that compose the equine gut microbiome and the interaction with their environment. Recent studies have identified the change in the composition of the intestinal microbiome during and after a colic episode, although is ...
Packed cell volume and heart rate to predict medical and surgical cases and their short-term survival in horses with gastrointestinal-induced colic.
The Canadian veterinary journal = La revue veterinaire canadienne    April 5, 2022   Volume 63, Issue 4 365-372 
Kos VK, Kramaric P, Brloznik M.The objective of this prospective case-control study of 125 horses with gastrointestinal tract-induced colic was to determine whether heart rate (HR) and packed cell volume (PCV) can predict surgical medical treatment and its short-term survival (time of discharge of the patient). Sixty-four horses were treated medically and 61 surgically (29 small intestinal and 32 large intestinal cases). At admission, both PCV and HR were higher in horses treated surgically than in horses treated medically; however, with longer duration of colic before presentation, the PCV was higher in the small intestin...
Strangulating left colon volvulus following nonsurgical castration in a 6-year-old donkey.
Veterinary research forum : an international quarterly journal    March 15, 2022   Volume 13, Issue 1 145-147 doi: 10.30466/vrf.2021.526717.3155
Azizi S, Masoudi H.Colic is a clinical syndrome and has been defined as a visceral abdominal pain and/or acute abdominal disease. It is a common cause of morbidity and mortality in horses. The most common forms of colics are related to gastrointestinal tract in nature and most often linked to colonic disturbances. However, colics are not well understood in donkeys compared to those of in horses and the literature is poor regarding bowel strangulating obstruction in donkeys. This report described the clinical signs and post-mortem necropsy findings of an abdominal colic due to the left colon volvulus following a ...
Clostridioides difficile infection and One Health: an equine perspective.
Environmental microbiology    January 21, 2022   Volume 24, Issue 3 985-997 doi: 10.1111/1462-2920.15898
Hain-Saunders NMR, Knight DR, Bruce M, Riley TV.Clostridioides (Clostridium) difficile presents a significant health risk to humans and animals. The complexity of the bacterial-host interaction affecting pathogenesis and disease development creates an ongoing challenge for epidemiological studies, control strategies and prevention planning. The recent emergence of human disease caused by strains of C. difficile found in animals adds to mounting evidence that C. difficile infection (CDI) may be a zoonosis. In equine populations, C. difficile is a known cause of diarrhoea and gastrointestinal inflammation, with considerable mortality and morb...
Effects of age, disease and anastomosis on short- and long-term survival after surgical correction of small intestinal strangulating diseases in 89 horses.
Equine veterinary journal    January 21, 2022   Volume 54, Issue 6 1031-1038 doi: 10.1111/evj.13558
Rudnick MJ, Denagamage TN, Freeman DE.Although survival rates have been reported after small intestinal surgery for strangulating diseases in horses, none have followed survival for periods relevant to the long lifespan of horses and none have described effect of age, disease and surgical treatments over such long survival periods. Objective: To examine effects of age, disease and type of surgery on long-term survival in horses after surgical treatment of small intestinal strangulating diseases over periods relevant to the expected lifespan of a horse. Methods: Retrospective clinical study. Methods: Post-operative data were gather...
A comprehensive and comparative proteomic analysis of horse serum proteins in colitis.
Equine veterinary journal    January 18, 2022   Volume 54, Issue 6 1039-1046 doi: 10.1111/evj.13554
Minamijima Y, Tozaki T, Kuroda T, Urayama S, Nomura M, Yamamoto K.Equine colitis is a diarrhoeal disease caused by inflammation of the large bowel and can potentially be life-threatening due to its rapid progression. Pathogenesis is multifactorial and pathophysiology is highly complicated, therefore, reliable diagnostic biomarkers are needed in the veterinary field. Objective: Serum is one of the most commonly used diagnostic tools in equine clinical investigation. To discover diagnostic or prognostic protein markers for colitis in horse serum, comprehensive and comparative proteomic analysis was conducted using liquid chromatography-tandem mass spectrometry...
Equine Squamous Gastric Disease: Prevalence, Impact and Management.
Veterinary medicine (Auckland, N.Z.)    December 31, 2021   Volume 12 381-399 doi: 10.2147/VMRR.S235258
Hewetson M, Tallon R.This narrative review explores the etiopathogenesis, clinical signs, diagnosis and treatment of ESGD (equine squamous gastric disease) and discusses the impact of this commonly encountered condition on the equine industry. ESGD refers specifically to peptic injury of the squamous mucosa of the stomach. Prevalence is highest in performance horses, but the disease has been documented across many breeds and ages, including in feral horses and foals. The pathogenesis of ESGD is well understood. Intensive management and exercise are important factors that contribute to a disruption of the normal st...
Age-Dependent Intestinal Repair: Implications for Foals with Severe Colic.
Animals : an open access journal from MDPI    November 23, 2021   Volume 11, Issue 12 doi: 10.3390/ani11123337
Erwin SJ, Blikslager AT, Ziegler AL.Colic is a leading cause of death in horses, with the most fatal form being strangulating obstruction which directly damages the intestinal barrier. Following surgical intervention, it is imperative that the intestinal barrier rapidly repairs to prevent translocation of gut bacteria and their products and ensure survival of the patient. Age-related disparities in survival have been noted in many species, including horses, humans, and pigs, with younger patients suffering poorer clinical outcomes. Maintenance and repair of the intestinal barrier is regulated by a complex mucosal microenvironmen...
Peritoneal bile acids concentration in adult horses with hepatic and gastrointestinal disorders.
Equine veterinary journal    November 19, 2021   Volume 54, Issue 5 914-921 doi: 10.1111/evj.13538
Rodríguez-Pozo ML, Armengou L, Viu J, Ríos J, Jose-Cunilleras E.Peritoneal bile acids concentration (PBAC) has not been previously reported in horses. A case of liver lobe torsion in which increased PBAC was detected prompted us to study PBAC in horses. Objective: (a) To determine a reference range of PBAC in horses; (b) to compare PBAC from horses with either hepatic or gastrointestinal disease and healthy horses and (c) to assess the prognostic and diagnostic values of PBAC. Methods: Prospective case-control. Methods: Prospective observational clinical study. Bile acids concentrations were measured in both plasma and peritoneal fluid in selected clinical...
An ethnoveterinary study of wild medicinal plants used by the Kyrgyz farmers.
Journal of ethnopharmacology    November 17, 2021   Volume 285 114842 doi: 10.1016/j.jep.2021.114842
Aldayarov N, Tulobaev A, Salykov R, Jumabekova J, Kydyralieva B, Omurzakova N, Kurmanbekova G, Imanberdieva N, Usubaliev B, Borkoev B, Salieva K....In their centuries-old nomadic life, since their livestock was the backbone of their lives, the Kyrgyz people used a variety of wild medicinal plants for ethnoveterinary practices. However, the plants used for the treatment of livestock ailments never have been recorded, except rarely in local publications. In this study, we present the HSHR (homemade single species herbal remedy reports), their methods of preparation and application, and the livestock ailments for which these remedies were used. Objective: The collect data from the five different high-altitude valleys of the Kyrgyz Republic o...
A pilot study evaluating the Calibrated Automated Thrombogram assay and application of plasma-thromboelastography for detection of hemostatic aberrations in horses with gastrointestinal disease.
BMC veterinary research    November 8, 2021   Volume 17, Issue 1 346 doi: 10.1186/s12917-021-03058-7
Honoré ML, Pihl TH, Nielsen LN.Critically ill horses, such as horses with gastrointestinal (GI) disease, often suffer from hemostatic aberrations. Global hemostatic tests examining the initiation of coagulation, clot strength and fibrinolysis, such as the Calibrated Automated Thrombogram (CAT) and plasma-thromboelastography (TEG) have not been evaluated in horses. This study aimed to evaluate CAT and apply plasma-TEG in horses. Test performance of CAT was evaluated on equine platelet poor plasma with intra- and inter-assay variability (CV) and a heparin dilution curve. To examine clinical performance of both tests, group co...
Equine grass sickness (a multiple systems neuropathy) is associated with alterations in the gastrointestinal mycobiome.
Animal microbiome    October 9, 2021   Volume 3, Issue 1 70 doi: 10.1186/s42523-021-00131-2
McGorum BC, Chen Z, Glendinning L, Gweon HS, Hunt L, Ivens A, Keen JA, Pirie RS, Taylor J, Wilkinson T, McLachlan G.Equine grass sickness (EGS) is a multiple systems neuropathy of grazing horses of unknown aetiology. An apparently identical disease occurs in cats, dogs, rabbits, hares, sheep, alpacas and llamas. Many of the risk factors for EGS are consistent with it being a pasture mycotoxicosis. To identify potential causal fungi, the gastrointestinal mycobiota of EGS horses were evaluated using targeted amplicon sequencing, and compared with those of two control groups. Samples were collected post mortem from up to 5 sites in the gastrointestinal tracts of EGS horses (EGS group; 150 samples from 54 horse...
Postoperative Ileus: Comparative Pathophysiology and Future Therapies.
Frontiers in veterinary science    September 13, 2021   Volume 8 714800 doi: 10.3389/fvets.2021.714800
Hellstrom EA, Ziegler AL, Blikslager AT.Postoperative ileus (POI), a decrease in gastrointestinal motility after surgery, is an important problem facing human and veterinary patients. 37.5% of horses that develop POI following small intestinal (SI) resection will not survive to discharge. The two major components of POI pathophysiology are a neurogenic phase which is then propagated by an inflammatory phase. Perioperative care has been implicated, namely the use of opioid therapy, inappropriate fluid therapy and electrolyte imbalances. Current therapy for POI variably includes an early return to feeding to induce physiological motil...
Ingestion of Soil by Grazing Sport Horses.
Animals : an open access journal from MDPI    July 15, 2021   Volume 11, Issue 7 doi: 10.3390/ani11072109
Jurjanz S, Collas C, Quish C, Younge B, Feidt C.Data on soil ingestion in horses are lacking in contrast to other free-range animals. The importance of soil as a vector for environmental pollutants to food is less relevant in horses but several disorders secondary to soil ingestion, such as sand colic or enteritis have been reported. Therefore, soil ingestion has been studied on Irish sport horses grazing at three offered levels of daily herbage: 2, 3 and 4% of their body weight. Soil ingestion was estimated by the faecal recovery of a soil natural marker. Horses had 4.5, 4.1 and 3.7% of soil in their total intake respectively for the 2, 3 ...
Perforations of tri-layer nitrile-latex and natural rubber latex gloves during ex-vivo equine intestinal anastomoses.
Veterinary surgery : VS    July 2, 2021   Volume 50, Issue 6 1250-1256 doi: 10.1111/vsu.13635
Averay K, Ward M, Verwilghen D.To compare perforation rates between tri-layer nitrile-latex and natural rubber latex surgical gloves after single-layer end-to-end jejunojejunal anastomoses in equine cadavers. Methods: Prospective randomized ex-vivo study. Methods: Pairs of surgical gloves (n = 46) worn during jejunojejunal anastomoses. Methods: Tri-layer nitrile-latex and rubber latex pairs of gloves were equally but randomly allocated to a right-handed surgeon performing 46 single-layer end-to-end jejunojejunal anastomoses on cadaveric material. Number and location of perforations were determined with the water leak test...
Comparison of the Fecal Microbiota of Horses with Intestinal Disease and Their Healthy Counterparts.
Veterinary sciences    June 17, 2021   Volume 8, Issue 6 doi: 10.3390/vetsci8060113
Park T, Cheong H, Yoon J, Kim A, Yun Y, Unno T.(1) Background: The intestinal microbiota plays an essential role in maintaining the host's health. Dysbiosis of the equine hindgut microbiota can alter the fermentation patterns and cause metabolic disorders. (2) Methods: This study compared the fecal microbiota composition of horses with intestinal disease and their healthy counterparts living in Korea using 16S rRNA sequencing from fecal samples. A total of 52 fecal samples were collected and divided into three groups: horses with large intestinal disease (n = 20), horses with small intestinal disease (n = 8), and healthy horses (n = 24). (...
Effect of three different needle holders on gastrointestinal anastomosis construction time and bursting pressure in equine jejunal segments.
BMC veterinary research    April 15, 2021   Volume 17, Issue 1 167 doi: 10.1186/s12917-021-02871-4
Averay K, van Galen G, Ward M, Verwilghen D.Equine small intestinal resection and anastomosis is a procedure where optimizing speed, without compromising integrity, is advantageous. There are a range of different needle holders available, but little is published on the impact surgical instrumentation has on surgical technique in veterinary medicine. The objectives of this study were to investigate if the needle holder type influences the anastomosis construction time, the anastomosis bursting pressure and whether the bursting pressure is influenced by the anastomosis construction time. Single layer end-to-end jejunojejunal anastomoses w...
Diagnostic and Clinical Course of Small Colon Recurrent Impaction Associated with Severe Myenteric Ganglionopathy in A Mare.
Journal of equine veterinary science    March 26, 2021   Volume 101 103453 doi: 10.1016/j.jevs.2021.103453
Ortolani F, Nannarone S, Sforna M, Gialletti R, Giglia G, Mandara MT.A 10-year-old Koninklijk Warmbloed Paardenstamboek Nederland (KWPN, Netherlands-based organization for registration of the Dutch Warmblood horses) mare was evaluated three times over four months because of recurrent colic. At every referral, a physical examination revealed a small colon impaction, which partially responded to food deprivation and oral administration of water and magnesium sulphate. Due to the recurrent nature of the small colon impaction, several differential diagnoses were considered: inflammatory bowel disease (IBD), chronic salmonellosis and myenteric ganglionopathies. At f...
Generation of a Biobank From Two Adult Thoroughbred Stallions for the Functional Annotation of Animal Genomes Initiative.
Frontiers in genetics    March 8, 2021   Volume 12 650305 doi: 10.3389/fgene.2021.650305
Donnelly CG, Bellone RR, Hales EN, Nguyen A, Katzman SA, Dujovne GA, Knickelbein KE, Avila F, Kalbfleisch TS, Giulotto E, Kingsley NB, Tanaka J....Following the successful creation of a biobank from two adult Thoroughbred mares, this study aimed to recapitulate sample collection in two adult Thoroughbred stallions as part of the Functional Annotation of the Animal Genome (FAANG) initiative. Both stallions underwent thorough physical, lameness, neurologic, and ophthalmic (including electroretinography) examinations prior to humane euthanasia. Epididymal sperm was recovered from both stallions immediately postmortem and cryopreserved. Aseptically collected full thickness skin biopsies were used to isolate, culture and cryopreserve dermal f...
Experimental crossover study on the effects of withholding feed for 24 h on the equine faecal bacterial microbiota in healthy mares.
BMC veterinary research    January 5, 2021   Volume 17, Issue 1 3 doi: 10.1186/s12917-020-02706-8
Willette JA, Pitta D, Indugu N, Vecchiarelli B, Hennessy ML, Dobbie T, Southwood LL.An association between equine gastrointestinal disease causing colic signs and changes in faecal bacterial microbiota has been identified. The reasons for these changes and their clinical relevance has not been investigated. Withholding feed, which is an integral part of managing horses with colic, may contribute to the observed changes in the microbiota and impact interpretation of findings in horses with colic. Study objectives were, therefore, to determine the effect of withholding feed for 24 h on equine faecal bacterial microbiota in healthy mares to differentiate the effects of withhol...
Interobserver and intraobserver reliability for 2 grading systems for gastric ulcer syndrome in horses.
Journal of veterinary internal medicine    December 7, 2020   Volume 35, Issue 1 571-579 doi: 10.1111/jvim.15987
Wise JC, Wilkes EJA, Raidal SL, Xie G, Crosby DE, Hale JN, Hughes KJ.Grading of equine gastric ulcer syndrome (EGUS) is undertaken in clinical and research settings, but the reliability of EGUS grading systems is poorly understood. Objective: Investigate interobserver and intraobserver reliability of an established ordinal grading system and a novel visual analog scale (VAS), and assess the influence of observer experience. Methods: Sixty deidentified gastroscopy videos. Methods: Six observers (3 specialists and 3 residents) graded videos using the EGUS Council (EGUC) system and VAS. Observers graded the videos three 3 for each system, using a cross-over design...
Estimation of Nitrite-Nitric Oxide Derivative-In Horses with Intestinal Colic by ESR Spectroscopy.
Veterinary sciences    November 29, 2020   Volume 7, Issue 4 191 doi: 10.3390/vetsci7040191
Borunova SF, Tkachev N, Iolchiev B, Artyushina Z, Abramov P, Nikitina M, Silanteva A, Khusnetdinova N, Serezhenkov V.Diseases of the gastrointestinal tract of horses are caused by many factors and have a complex pathogenesis. Developing effective methods of differential diagnostics is of high fundamental and applied importance. The pathogenesis of diseases of the digestive tract of horses accompanied by the development of inflammation and oxidative stress, can be associated with a lack of the nitrogen monoxide which controls many signaling pathways in the body. The level of the nitric oxide (NO) is involved in the regulation of the immune and nervous systems, the tone of all the blood vessels, and the course...
An atypical presentation of a mesenteric Meckel’s diverticulum in a 7-year-old warmblood mare: case report.
BMC veterinary research    October 29, 2020   Volume 16, Issue 1 409 doi: 10.1186/s12917-020-02631-w
Stas E, Kranenburg L, Witt P, de Grauw J, van den Brand J, Ensink J, Brommer H.Meckel's diverticula are a rare cause of small intestinal strangulation, diagnosed at laparotomy or necropsy. This congenital anomaly of the gastrointestinal tract originates from a remnant of the vitelline duct. In reported equine cases, they present as a full-thickness diverticulum on the antimesenteric border of the distal jejunum or proximal ileum. Methods: On laparotomy a Meckel's diverticulum positioned at the mesenteric side was found to be the cause of small intestinal strangulation. This position is very uncommon and to the best knowledge of the authors there is no unambiguous descrip...
Multiple resistance in equine cyathostomins: a case study from military establishments in Rio Grande do Sul, Brazil. Flores AG, Osmari V, Ramos F, Marques CB, Ramos DJ, Botton SA, Vogel FSF, Sangioni LA.Semi-intensive equine breeding system favors gastrointestinal nematode infections. The treatment of these infections is based on the use of anthelmintics. However, the inappropriate use of these drugs has led to parasitic resistance to the available active principles. The objective of this study was to evaluate the efficacy of the main classes of antiparasitic (ATP) used in control in adult and young animals, including: benzimidazoles (fenbendazole), pyrimidines (pyrantel pamoate), macrocyclic lactones (ivermectin and moxidectin), as well as the combination of active ingredients (ivermectin + ...
A wireless endoscopy capsule suitable for imaging of the equine stomach and small intestine.
Journal of veterinary internal medicine    June 8, 2020   Volume 34, Issue 4 1622-1630 doi: 10.1111/jvim.15825
Steinmann M, Bezugley RJ, Bond SL, Pomrantz JS, Léguillette R.Capsule endoscopy offers a new method for visualization of the gastrointestinal mucosa in horses where other imaging technologies have diagnostic limitations. Objective: To (1) test the feasibility of using this novel endoscopy capsule to visualize intestinal mucosa in horses, including an objective assessment of image quality, (2) assess how changes in preadministration preparation affect the transit time and the amount of gastrointestinal mucosa visualized, and (3) describe intestinal mucosa lesions in healthy horses. Methods: Five healthy adult horses. Methods: Three protocols were used in ...
The cecal and fecal microbiomes and metabolomes of horses before and after metronidazole administration.
PloS one    May 22, 2020   Volume 15, Issue 5 e0232905 doi: 10.1371/journal.pone.0232905
Arnold CE, Isaiah A, Pilla R, Lidbury J, Coverdale JS, Callaway TR, Lawhon SD, Steiner J, Suchodolski JS.Antibiotic administration can be a cause of gastrointestinal disease in horses, creating a disruption in the normal population and function of bacteria found in the hindgut. The objective of this study was to describe the changes in the cecal and fecal microbiomes and metabolomes of clinically healthy horses before and after metronidazole administration. Metronidazole (15 mg/kg BID PO) was given to five horses with cecal cannulas. The study was suspended on Day 3 due to adverse gastrointestinal effects. Cecal and fecal samples were obtained before (Days minus52, m28, m14, and 0) and after (Day...
Parasite Occurrence and Parasite Management in Swedish Horses Presenting with Gastrointestinal Disease-A Case-Control Study.
Animals : an open access journal from MDPI    April 7, 2020   Volume 10, Issue 4 638 doi: 10.3390/ani10040638
Hedberg-Alm Y, Penell J, Riihimäki M, Osterman-Lind E, Nielsen MK, Tydén E.All grazing horses are exposed to intestinal parasites, which have the potential to cause gastrointestinal disease. In Sweden, there is a concern about an increase in parasite-related equine gastrointestinal disease, in particular , since the implementation of prescription-only anthelmintics approximately 10 years ago. In a prospective case-control study, parasitological status, using fecal analyses for strongyle egg counts, the presence of eggs and Polymerase chain reaction (PCR) as well as serology for , were compared between horses presenting with or without gastrointestinal disease at a ...
Evaluation of Fecal Sand Clearance in Horses With Naturally Acquired Colonic Sand Accumulation With a Product Containing Probiotics, Prebiotics, and Psyllium.
Journal of equine veterinary science    March 2, 2020   Volume 90 102970 doi: 10.1016/j.jevs.2020.102970
Hassel DM, Curley T, Hoaglund EL.Consumption of sand and dirt in horses can cause chronic diarrhea and colic because of irritation and obstruction of the gastrointestinal tract of horses. Prevention has primarily focused on changes in management to reduce the intake of sand and feeding of psyllium products. The purpose of this study was to evaluate the efficacy of a product containing probiotics, prebiotics, and psyllium in the clearance of colonic sand in horses with naturally acquired sand accumulation using a randomized, placebo-controlled, blinded clinical trial format. After identification of 10 horses with sand accumula...
Usefulness of a Point-of-Care Analyzer to Measure Cardiac Troponin I and D-Dimer Concentrations in Critically Ill Horses With Gastrointestinal Diseases.
Journal of equine veterinary science    February 27, 2020   Volume 90 102965 doi: 10.1016/j.jevs.2020.102965
Martín-Cuervo M, Aguirre CN, Gracia LA, Barrera R, Ezquerra LJ, Martinez-Subiela S, Cerón JJ.Point-of-care (POC) systems for the joint measurement of Troponin and D-dimers have not been studied in horses. The aim of this study was to perform the validation of a POC system (AQT90 FLEX) for the measurement of cardiac troponin I (cTnI) and D-dimers in the serum of horses with gastrointestinal diseases. The main objective was to evaluate whether or not this system can distinguish healthy animals from diseased animals. A sample of 33 horses was included in the study: control group (n = 10) and horses with gastrointestinal disorders (n = 21), which were classified according to their outco...