You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
non - variceal upper gastrointestinal bleeding ( nvugib ) is defined as gastrointestinal ( gi ) hemorrhage originating proximal to the ligament of treitz in the duodenum .
while there are myriad sources for nvugib ( such as gastroduodenal erosions , mallory - weiss tears , vascular malformations , and severe esophagitis ) , peptic ulcer bleeding remains the single most common cause , accounting for 25% to 67% of the sources of nvugib . according to the nationwide inpatient sample , the largest inpatient care database in the united states ,
the incidence of nvugib has shown a steady decline over the last two decades , from 108 to 78 cases per 100,000 .
this decrease in the incidence of nvugib has also translated into a decline in the in - hospital mortality rate ; the case fatality rate of all non - variceal causes of upper gi bleeding declined from 4.5% in the late 1980s to 2.1% in the 2000s .
better understanding of the importance of aggressive hemodynamic resuscitation , prompt initiation of pharmacologic intervention ( i.e. , proton pump inhibitor [ ppi ] ) , and improved efficacy of endoscopic hemostasis have contributed to this positive outcome .
given the imperative therapeutic role of pharmacologic and endoscopic management in achieving hemostasis in nvugib , new modalities to improve the current treatment strategies continue to be developed .
this review aims to identify some of the newer techniques as juxtaposed with the current therapeutic options .
various medications are used to either augment initial hemostasis or prevent the recurrence of bleeding during the same period of hospitalization .
it is known that an intragastric ph of 6 or lower can convert pepsinogen to pepsin , which can cause disaggregation of platelet - rich clots formed at the source of mucosal breakdown . on this basis ,
attempts to achieve gastric ph neutrality via pharmacologic intervention have been one of the foundations of initial management of gi bleeding .
a review of 24 trials found that ppis significantly reduced rebleeding , the need for repeat endoscopic therapy , and the requirement for surgery . despite these advantages
this could be attributed to the fact that ppis are more useful in the maintenance of hemostasis rather than in initiating the hemostatic cascade .
hence , since most mortality related to upper gi hemorrhage occurs because of an inability to achieve initial hemostasis ( either spontaneous or via endoscopic , angiographic , or surgical intervention ) , ppis will not influence the mortality outcome in a statistically significant manner . while ppis certainly have their role in the armamentarium of nvugib , various dosing regimens and routes of administration ( intravenous or oral ) have been used .
in fact , a cochrane database review of 22 randomized controlled trials on various dosing regimens and routes ( oral or intravenous ) of administration found no difference with respect to rebleeding , repeat endoscopic therapy , need for emergency surgery , or mortality .
given this lack of clear benefit in prolonged iv administration and the substantially higher cost associated with intravenous ppis , the current recommendation is to institute an oral ppi regimen as early as possible . in contrast
, there is much debate regarding the use of tranexamic acid ( txa ; brand name , lysteda ; ferring pharmaceuticals inc . , st .
prex , switzerland ) in the management of acute nvugib . as a derivative of the amino acid lysine
, it acts as an antifibrinolytic agent by inhibiting the action of plasmin . owing to its role in the coagulation cascade
, txa has been used in circumstances requiring acute reduction of excessive blood loss from postpartum hemorrhage and also from iatrogenic causes such as bleeding after oral surgery . while some studies have suggested a mortality benefit when txa is used in the management of upper gi , other studies performed since the advent of ppi therapy seem to provide a less robust degree of benefit , ultimately challenging its usefulness in the ppi era . moreover , some concerns remain regarding the durability and consistency of its thrombogenic potential in acidic environments . given the lack of high - quality evidence , the routine use of txa is not currently recommended in general clinical practice . the hemorrhage alleviation with tranexamic acid - intestinal system ( halt - it ) trial , a large randomized
, double - blind , placebo - controlled trial ( clinicaltrials.gov nct01658124 ) , is being conducted to clarify this issue by comparing patients administered txa with those administered placebo , in order to quantify the effects of early administration of txa on mortality , necessity for angiographic embolization and surgery , blood transfusion requirements , and risk of thromboembolic disease .
in general , endoscopic hemostasis relies either on the ablation of a bleeding vessel / lesion ( thermal ablative method ) or on mechanical tamponade of a bleeding source ( see below ) . to improve the outcome of endoscopic hemostasis
, various types of thermal ablative catheters and mechanical hemostatic tools ( such as endoscopic hemoclips and multi - band ligators ) were developed over the last three decades .
this , in turn , resulted in an improved success rate of endoscopic hemostasis and a reduction in blood transfusion requirements . while proven to be effective and safe in managing most focal sources of nvugib , these methods are often inadequate when the bleeding source is atypical ( such as tumor - related bleeding ) , multifocal , or diffuse . with respect to endoscopically delivered pharmacotherapy , a number of topical hemostatic agents have been developed and incorporated into disposable endoscopic devices in recent years .
the concept of topical application of hemostatic agents is attractive , as it is a non - traumatic method of hemostasis ( i.e. , no further destruction of the surrounding tissue during an attempt of hemostasis ) that can be applied to a diffuse , multifocal source of bleeding .
the significance of this type of hemostatic method is that endoscopic hemostasis can now reach beyond addressing single or focal sources of nvugib , such as peptic ulcer bleeding , towards the management of bleeding lesions that were not amenable to previous methods .
hemospray ( otherwise known as tc-325 ; cook medical , bloomington , in , usa ) is an inorganic , non - absorbable nano - compound sprayed through a catheter that is inserted into the working channel of an endoscope ( through - the - scope method ) .
the powder is delivered with the aid of a pressurized co2 canister to a desired location .
small randomized and observational studies have demonstrated the efficacy and safety of hemospray in managing bleeding from peptic ulcers as well as other iatrogenic etiologies . when hemospray was used for various causes of nvugib
, a review of all prospective and retrospective studies , and case series showed an immediate hemostasis of 92.3% , with a 7-day rebleeding rate of 20.6% .
given this proven short - term benefit , some european , asian , and american countries have approved the use of hemospray as part of their arsenal of endoscopic hemostasis . however , in the united states , it is unavailable at present and is pending u s food and drug administration ( fda ) review . the endoclot ( endoclot plus inc . ,
santa clara , ca , usa ) polysaccharide hemostatic system is another non - contact endoscopic device that delivers hemostatic powder .
as it is composed of absorbable modified polymer ( amp ) particles , it absorbs water from blood .
this dehydration process increases the concentration of platelets , red blood cells , and coagulation proteins ( thrombin , fibrinogen , etc . ) , resulting in the rapid formation of a hemostatic layer .
this device primarily originated outside of the united states , and multiple small studies have demonstrated its potential efficacy and safety in managing nvugib .
ankaferd blood stopper ( abs ; ankaferd health products , istanbul , turkey ) is a 100-ml herbal extract composed of five different plant species , namely 9 mg of glycyrrhiza glabra ( dried leaf extract ) , 5 mg of thymus vulgaris ( dried grass extract ) , 7 mg of alpinia officinarum ( dried leaf extract ) , 6 mg of urtica dioica ( dried root extract ) , and 8 mg of vitis vinifera ( dried leaf extract ) .
the exact mechanism of action of abs is unknown , but it is purported to form an encapsulated web of erythrocyte aggregation .
while abs has not been approved by the fda , one retrospective observational series of 26 patients showed that its application via a disposable wash pipe was effective in all cases except spurting arterial bleeding .
it is important to iterate that all aforementioned hemostatic compounds are at best a temporary remedy , providing short - term hemostasis , and that long - term hemostasis relies on mucosal healing under the hemostatic plug created by these various compounds .
conventional therapy for treatment of various forms of nvugib includes injectants ( specifically epinephrine to achieve tamponade ) , mechanical therapy ( specifically endoscopic clips ) , and cautery ( including heater , monopolar , and bipolar electrocautery ) , which cause coaptation , and argon plasma coagulation , which causes coagulation in the absence of mechanical contact .
it is imperative to recognize that monotherapy , which relies only on the injection of a vasoconstrictive substance , is inadequate in achieving a meaningful long - term hemostasis , with an unacceptable risk of recurrent bleeding and a significantly higher rate of requirement of surgical intervention . on comparing these various modalities , specifically with respect to ulcer bleeding , thermal therapy or clips
are found to outperform epinephrine monotherapy , whereas epinephrine plus an additional modality outperform epinephrine monotherapy .
thermal ablative methods and mechanical hemostasis as monotherapy have resulted in a largely comparable rate of successful endoscopic hemostasis .
new technologies have been developed to address and optimize the treatment of nvugib with respect to mechanical endoscopic hemostasis .
the otsc , otherwise known as the  bear claw ,  comes in various dimensions with blunt or sharp closure jaws .
similar in deployment to the variceal banding kit , the opposing ends of a bleeding lesion are suctioned into the endoscopic apparatus with subsequent deployment of the device . while prospective randomized clinical trials have yet to be performed , the largest case series in the literature to date included 30 consecutive patients with either upper or lower gi bleeding refractory to conventional endoscopic techniques ( defined as epinephrine injection and through - the - scope clips ) .
initial hemostasis was achieved in 97% of the patients , with one patient requiring interventional radiology embolization from a duodenal bulb ulcer .
these results were , thus , in favor of otsc as a useful modality when conventional hemostatic therapy has failed .
another technology that is gaining acceptance is radiofrequency ablation ( rfa ) , particularly in the setting of gastric antral vascular ectasia ( gave ) . using uniform thermal energy in a superficial manner ,
rfa has been used to treat gave refractory to argon plasma coagulation . in an open - label prospective cohort study , 21 patients with transfusion - dependent gave underwent rfa , with 18 of them achieving transfusion independence .
similarly , in an open - label , retrospective case series , 24 patients with gave underwent rfa , and 15 became transfusion independent at 6 months .
cryotherapy , a modality that uses compressed carbon dioxide or liquid nitrogen to freeze tissues and cause superficial necrosis , has also been used in patients with refractory gave . in one pilot study that assessed 12 patients with gave and anemia ,
50% of the patients achieved a complete response , while the rest achieved a partial response with decreased transfusion requirements .
however , the best delivery system and the number of treatments required still remain unclear .
in summary , several pharmacologic and endoscopic modalities exist in the endoscopist s armamentarium for nvugib .
targeted pharmacological and endoscopic therapies include epinephrine as well as endoscopic ablative treatment and mechanical tamponade .
multifocal lesions that are difficult to control with targeted therapy have prompted a burgeoning of hemostatic powder delivery systems that afford the endoscopist the ability to achieve hemostatic control when the location and/or number of lesions render the targeted therapy less advantageous .
while some modalities have not been approved by the fda at this juncture , improved technique , device design , and pharmacologic adjuncts will enhance outcomes with respect to hemostatic control achieved by the index endoscopic intervention .
non - variceal upper gastrointestinal bleeding , the most common etiology of which is peptic ulcer disease , remains a persistent challenge despite a reduction in both its incidence and mortality . 
 both pharmacologic and endoscopic techniques have been developed to achieve hemostasis , with varying degrees of success . among the pharmacologic therapies , 
 proton pump inhibitors remain the mainstay of treatment , as they reduce the risk of rebleeding and requirement for recurrent endoscopic evaluation . 
 tranexamic acid , a derivative of the amino acid lysine , is an antifibrinolytic agent whose role requires further investigation before application . 
 endoscopically delivered pharmacotherapy , including hemospray ( cook medical ) , endoclot ( endoclot plus inc . ) , and ankaferd blood stopper ( ankaferd health products ) , in addition to standard epinephrine , show promise in this regard , although their mechanisms of action require further investigation . 
 non - pharmacologic endoscopic techniques use one of the following two methods to achieve hemostasis : ablation or mechanical tamponade , which may involve using endoscopic clips , cautery , argon plasma coagulation , over - the - scope clipping devices , radiofrequency ablation , and cryotherapy . 
 this review aimed to highlight these novel and fundamental hemostatic strategies and the research supporting their efficacy .