Acute mesenteric ischemia: guidelines of the World Society of Emergency Surgery

Miklosh Bala, Jeffry Kashuk, Ernest E Moore, Yoram Kluger, Walter Biffl, Carlos Augusto Gomes, Offir Ben-Ishay, Chen Rubinstein, Zsolt J Balogh, Ian Civil, Federico Coccolini, Ari Leppaniemi, Andrew Peitzman, Luca Ansaloni, Michael Sugrue, Massimo Sartelli, Salomone Di Saverio, Gustavo P Fraga, Fausto Catena, Miklosh Bala, Jeffry Kashuk, Ernest E Moore, Yoram Kluger, Walter Biffl, Carlos Augusto Gomes, Offir Ben-Ishay, Chen Rubinstein, Zsolt J Balogh, Ian Civil, Federico Coccolini, Ari Leppaniemi, Andrew Peitzman, Luca Ansaloni, Michael Sugrue, Massimo Sartelli, Salomone Di Saverio, Gustavo P Fraga, Fausto Catena

Abstract

Acute mesenteric ischemia (AMI) is typically defined as a group of diseases characterized by an interruption of the blood supply to varying portions of the small intestine, leading to ischemia and secondary inflammatory changes. If untreated, this process will eventuate in life threatening intestinal necrosis. The incidence is low, estimated at 0.09-0.2% of all acute surgical admissions. Therefore, although the entity is an uncommon cause of abdominal pain, diligence is always required because if untreated, mortality has consistently been reported in the range of 50%. Early diagnosis and timely surgical intervention are the cornerstones of modern treatment and are essential to reduce the high mortality associated with this entity. The advent of endovascular approaches in parallel with modern imaging techniques may provide new options. Thus, we believe that a current position paper from World Society of Emergency Surgery (WSES) is warranted, in order to put forth the most recent and practical recommendations for diagnosis and treatment of AMI. This review will address the concepts of AMI with the aim of focusing on specific areas where early diagnosis and management hold the strongest potential for improving outcomes in this disease process. Some of the key points include the prompt use of CT angiography to establish the diagnosis, evaluation of the potential for revascularization to re-establish blood flow to ischemic bowel, resection of necrotic intestine, and use of damage control techniques when appropriate to allow for re-assessment of bowel viability prior to definitive anastomosis and abdominal closure.

Keywords: Guidelines; Mesenteric angiography; Mesenteric arterial occlusion; Mesenteric artery stenting; Mesenteric ischemia; Recommendations; Small bowel ischemia.

Conflict of interest statement

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Selected image from a CTA scan of a patient with acute mesenteric ischemia secondary to occluded SMA from an embolic source (arrow). 3D reconstruction is demonstrates mid occlusion of SMA (arrow)
Fig. 2
Fig. 2
30-year-old patient with acute superior mesenteric vein a and portal vein thrombosis b due to hypercoagulable state. No signs of bowel ischemia were noted, and the patient was treated successfully with long-term anticoagulation
Fig. 3
Fig. 3
Patient with acute thrombosis of SMA underwent left ileo–SMA bypass with a common femoral vein graft

References

    1. Patel A, Kaleya RN, Sammartano RJ. Pathophysiology of mesenteric ischemia. Surg Clin North Am. 1992;72:31–41. doi: 10.1016/S0039-6109(16)45626-4.
    1. Acosta S. Mesenteric ischemia. Curr Opin Crit Care. 2015;21:171–178. doi: 10.1097/MCC.0000000000000189.
    1. Clair DG, Beach JM. Mesenteric Ischemia. N Engl J Med. 2016;374:959–968. doi: 10.1056/NEJMra1503884.
    1. Acosta S, Bjorck M. Acute thrombo-embolic occlusion of the superior mesenteric artery: a prospective study in a well-defined population. Eur J Vasc Endovasc Surg. 2003;26:179–183. doi: 10.1053/ejvs.2002.1893.
    1. Duran M, Pohl E, Grabitz K, Schelzig H, Sagban TA, Simon F. The importance of open emergency surgery in the treatment of acute mesenteric ischemia. World J Emerg Surg. 2015;26:10–45.
    1. Stoney RJ, Cunningham CG. Acute mesenteric ischemia. Surgery. 1993;114:489–490.
    1. Chang RW, Chang JB, Longo WE. Update in management of mesenteric ischemia. World J Gastroenterol. 2006;12:3243–3247. doi: 10.3748/wjg.v12.i20.3243.
    1. Horton KM, Fishman EK. Multidetector CT angiography in the diagnosis of mesenteric ischemia. Radiol Clin N Am. 2007;45:275–288. doi: 10.1016/j.rcl.2007.03.010.
    1. Schoots IG, Koffeman GI, Legemate DA, Levi M, van Gulik TM. Systematic review of survival after acute mesenteric ischaemia according to disease aetiology. Br J Surg. 2004;91:17–27. doi: 10.1002/bjs.4459.
    1. Beaulieu RJ, Arnaoutakis KD, Abularrage CJ, Efron DT, Schneider E, Black JH. Comparison of open and endovascular treatment of acute mesenteric ischemia. J Vasc Surg. 2014;59:159–164. doi: 10.1016/j.jvs.2013.06.084.
    1. Rosenblum JD, Boyle CM, Schwartz LB. The mesenteric circulation. Anatomy and physiology. Surg Clin North Am. 1997;77:289–306. doi: 10.1016/S0039-6109(05)70549-1.
    1. Haglund U, Bergqvist D. Intestinal ischemia—the basics. Langenbeck's Arch Surg. 1999;384:233–238. doi: 10.1007/s004230050197.
    1. van Petersen AS, Kolkman JJ, Meerwaldt R, Huisman AB, van der Palen J, Zeebregts CJ, Geelkerken RH. Mesenteric stenosis, collaterals, and compensatory blood flow. J Vasc Surg. 2014;60:111–119. doi: 10.1016/j.jvs.2014.01.063.
    1. Acosta S, Ogren M, Sternby NH, Bergqvist D, Björck M. Clinical implications for the management of acute thromboembolic occlusion of the superior mesenteric artery: autopsy findings in 213 patients. Ann Surg. 2005;241:516–522. doi: 10.1097/01.sla.0000154269.52294.57.
    1. Kärkkäinen JM, Acosta S. Acute mesenteric ischemia (part I) -incidence, etiologies, and how to improve early diagnosis. Best Pract Res Clin Gastroenterol. 2017;31:15–25. doi: 10.1016/j.bpg.2016.10.018.
    1. Aschoff AJ, Stuber G, Becker BW, Hoffmann MH, Schmitz BL, Schelzig H, et al. Evaluation of acute mesenteric ischemia: accuracy of biphasic mesenteric multi-detector CT angiography. Abdom Imaging. 2009;34:345–357. doi: 10.1007/s00261-008-9392-8.
    1. Moore HB, Moore EE, Lawson PJ, Gonzalez E, Fragoso M, Morton AP, Gamboni F, Chapman MP, Sauaia A, Banerjee A, Silliman CC. Fibrinolysis shutdown phenotype masks changes in rodent coagulation in tissue injury versus hemorrhagic shock. Surgery. 2015;158:386–392. doi: 10.1016/j.surg.2015.04.008.
    1. Cohn DM, Roshani S, Middeldorp S. Thrombophilia and venous thromboembolism: implications for testing. Semin Thromb Hemost. 2007;33:573–581. doi: 10.1055/s-2007-985753.
    1. Carver TW, Vora RS, Taneja A. Mesenteric ischemia. Crit Care Clin. 2016;32:155–171. doi: 10.1016/j.ccc.2015.11.001.
    1. Park WM, Gloviczki P, Cherry KJ, Jr, Hallett JW, Jr, Bower TC, Panneton JM, Schleck C, Ilstrup D, Harmsen WS, Noel AA. Contemporary management of acute mesenteric ischemia: Factors associated with survival. J Vasc Surg. 2002;35:445–452. doi: 10.1067/mva.2002.120373.
    1. Acosta-Merida MA, Marchena-Gomez J, Hemmersbach-Miller M, Roque-Castellano C, Hernandez-Romero JM. Identification of risk factors for perioperative mortality in acute mesenteric ischemia. World J Surg. 2006;30:1579–1585. doi: 10.1007/s00268-005-0560-5.
    1. Morasch MD, Ebaugh JL, Chiou AC, Matsumura JS, Pearce WH, Yao JS. Mesenteric venous thrombosis: a changing clinical entity. J Vasc Surg. 2001;34:680–684. doi: 10.1067/mva.2001.116965.
    1. Oliva IB, Davarpanah AH, Rybicki FJ, Desjardins B, Flamm SD, Francois CJ, Gerhard-Herman MD, Kalva SP, Ashraf Mansour M, Mohler ER, 3rd, Schenker MP, Weiss C, Dill KE. ACR Appropriateness Criteria® imaging of mesenteric ischemia. Abdom Imaging. 2013;38:714–719. doi: 10.1007/s00261-012-9975-2.
    1. Kougias P, Lau D, El Sayed HF, Zhou W, Huynh TT, Lin PH. Determinants ofmortality and treatment outcome following surgical interventions for acutemesenteric ischemia. J Vasc Surg. 2007;46:467–474. doi: 10.1016/j.jvs.2007.04.045.
    1. Nuzzo A, Maggiori L, Ronot M, Becq A, Plessier A, Gault N, Joly F, Castier Y, Vilgrain V, Paugam C, Panis Y, Bouhnik Y, Cazals-Hatem D, Corcos O. Predictive factors of intestinal necrosis in acute mesenteric ischemia: prospective study from an intestinal stroke center. Am J Gastroenterol. 2017;112:597–605. doi: 10.1038/ajg.2017.38.
    1. Evennett NJ, Petrov MS, Mittal A, Windsor JA. Systematic review and pooled estimates for the diagnostic accuracy of serological markers for intestinal ischemia. World J Surg. 2009;33:1374–1383. doi: 10.1007/s00268-009-0074-7.
    1. Powell A, Armstrong P. Plasma biomarkers for early diagnosis of acuteintestinal ischemia. Semin Vasc Surg. 2014;27:170–175. doi: 10.1053/j.semvascsurg.2015.01.008.
    1. Block T, Nilsson TK, Björck M, Acosta S. Diagnostic accuracy of plasma biomarkers for intestinal ischaemia. Scand J Clin Lab Invest. 2008;68:242–248. doi: 10.1080/00365510701646264.
    1. Wilson C, Imrie CW. Amylase and gut infarction. Br J Surg. 1986;73:219–221. doi: 10.1002/bjs.1800730322.
    1. Matsumoto S, Sekine K, Funaoka H, Yamazaki M, Shimizu M, Hayashida K, Kitano M. Diagnostic performance of plasma biomarkers in patients with acute intestinal ischaemia. Br J Surg. 2014;101:232–238. doi: 10.1002/bjs.9331.
    1. Treskes N, Persoon AM, van Zanten ARH. Diagnostic accuracy of novel serological biomarkers to detect acute mesenteric ischemia: a systematic review and meta-analysis. Intern Emerg Med. 2017. [Epub ahead of print].
    1. Bradbury AW, Brittenden J, McBride K, Ruckley CV. Mesenteric ischaemia: a multidisciplinary approach. Br J Surg. 1995;82:1446–1459. doi: 10.1002/bjs.1800821105.
    1. Kassahun WT, Schulz T, Richter O, Hauss J. Unchanged high mortality rates from acute occlusive intestinal ischemia: six year review. Langenbeck's Arch Surg. 2008;393:163–171. doi: 10.1007/s00423-007-0263-5.
    1. Kirkpatrick ID, Kroeker MA, Greenberg HM. Biphasic CT with mesenteric CTangiography in the evaluation of acute mesenteric ischemia: initial experience. Radiology. 2003;229:91–98. doi: 10.1148/radiol.2291020991.
    1. Furukawa A, Kanasaki S, Kono N, Wakamiya M, Tanaka T, Takahashi M, Murata K. CT diagnosis of acute mesenteric ischemia from various causes. Am J Roentgenol. 2009;192:408–416. doi: 10.2214/AJR.08.1138.
    1. Menke J. Diagnostic accuracy of multidetector CT in acute mesenteric ischemia: systematic review and meta-analysis. Radiology. 2010;256:93–101. doi: 10.1148/radiol.10091938.
    1. Hagspiel KD, Flors L, Hanley M, Norton PT. Computed tomography angiography and magnetic resonance angiography imaging of the mesenteric vasculature. Tech Vasc Interv Radiol. 2015;18:2–13. doi: 10.1053/j.tvir.2014.12.002.
    1. Oliva IB, Davarpanah AH, Rybicki FJ, et al. ACR appropriateness criteria imaging of mesenteric ischemia. Abdom Imaging. 2013;38:714–719. doi: 10.1007/s00261-012-9975-2.
    1. David RA, Erben Y, Kalra M. Clinical presentation, etiology, and diagnostic considerations. In: Oderich G, editor. Mesenteric Vascular Disease. New York: Springer; 2015. pp. 199–209.
    1. Daviaud F, Grimaldi D, Dechartres A, Charpentier J, Geri G, Marin N, Chiche JD, Cariou A, Mira JP, Pène F. Timing and causes of death in septic shock. Ann Intensive Care. 2015;5:16. doi: 10.1186/s13613-015-0058-8.
    1. Guillaume A, Pili-Floury S, Chocron S, Delabrousse E, De Parseval B, Koch S, Samain E, Capellier G, Piton G. Acute mesenteric ischemia among post-cardiac surgery patients presenting with multiple organ failure. Shock. 2016. [Epub ahead of print].
    1. Mastoraki A, Mastoraki S, Tziava E, Touloumi S, Krinos N, Danias N, Lazaris A, Arkadopoulos N. Mesenteric ischemia: pathogenesis and challenging diagnostic and therapeutic modalities. World J Gastrointest Pathophysiol. 2016;7:125–130. doi: 10.4291/wjgp.v7.i1.125.
    1. Mogilner JG, Bitterman H, Hayari L, et al. Effect of elevated intra-abdominal pressure and hyperoxia on portal vein blood flow, hepatocyte proliferation and apoptosis in a rat model. Eur J Pediatr Surg. 2008;18:380–386. doi: 10.1055/s-2008-1038920.
    1. Wyers MC. Acute mesenteric ischemia: diagnostic approach and surgical treatment. Semin Vasc Surg. 2010;23:9–20. doi: 10.1053/j.semvascsurg.2009.12.002.
    1. Corcos O, Nuzzo A. Gastro-intestinalvascular emergencies. Best Pract Res Clin Gastroenterol. 2013;27:709–725. doi: 10.1016/j.bpg.2013.08.006.
    1. Tendler DA, LaMont JT. Acute mesenteric ischemia. Uptodate. 2013. . Accessed 13 Aug 2016.
    1. Sise MJ. Mesenteric ischemia: the whole spectrum. Scand J Surg. 2010;99:106–110. doi: 10.1177/145749691009900212.
    1. Oldenburg WA, Lau LL, Rodenberg TJ, Edmonds HJ, Burger CD. Acute mesentericischemia: a clinical review. Arch Intern Med. 2004;164:1054–1062. doi: 10.1001/archinte.164.10.1054.
    1. Helmerhorst HJ, Schultz MJ, van der Voort PH, de Jonge E, van Westerloo DJ. Bench-to-bedside review: the effects of hyperoxia during critical illness. Crit Care. 2015;19:284. doi: 10.1186/s13054-015-0996-4.
    1. Silvestri L, van Saene HK, Zandstra DF, Marshall JC, Gregori D, Gullo A. Impactof selective decontamination of thedigestive tract on multiple organ dysfunctionsyndrome: systematic review of randomizedcontrolled trials. Crit Care Med. 2010;38:1370–1376. doi: 10.1097/CCM.0b013e3181d9db8c.
    1. Schoots IG, Levi MM, Reekers JA, Lameris JS, van Gulik TM. Thrombolytic therapy for acute superior mesenteric artery occlusion. J Vasc Interv Radiol. 2005;16:317–329. doi: 10.1097/01.RVI.0000141719.24321.0B.
    1. Landis MS, Rajan DK, Simons ME, Hayeems EB, Kachura JR, Sniderman KW. Percutaneous management of chronic mesenteric ischemia: outcomes after intervention. J Vasc Interv Radiol. 2005;16:1319–1325. doi: 10.1097/01.RVI.0000171697.09811.0E.
    1. Sarac TP. Techniques of endovascular revascularization for acute mesenteric ischemia. In: Oderich G, editor. Mesenteric Vascular Disease. New York: Springer; 2015. pp. 241–252.
    1. Kim BG, Ohm JY, Bae MN, Kim HN, Kim YJ, Chung MH, Park CS, Ihm SH, Kim HY. Successful percutaneous aspiration thrombectomy for acute mesenteric ischemia in a patient with atrial fibrillation despite optimal anticoagulation therapy. Can J Cardiol. 2013;29:1329.e5–1329.e7. doi: 10.1016/j.cjca.2012.12.008.
    1. Schoenbaum SW, Pena C, Koenigsberg P, Katzen BT. Superior mesenteric artery embolism: treatment with intra arterial urokinase. JVIR. 1992;3:485–490. doi: 10.1016/S1051-0443(92)71997-6.
    1. Simó G, Echenagusia AJ, Camuñez F, Turégano F, Cabrera A, Urbano J. Superior mesenteric arterial embolism: local fibrinolytic treatment with urokinase. Radiology. 1997;204:775–779. doi: 10.1148/radiology.204.3.9280258.
    1. Jia Z, Jiang G, Tian F, Zhao J, Li S, Wang K, Wang Y, Jiang L, Wang W. Early endovascular treatment of superior mesenteric occlusion secondary to thromboemboli. Eur J Vasc Endovasc Surg. 2014;47:196–203. doi: 10.1016/j.ejvs.2013.09.025.
    1. Orr NT, Endean ED. Part two: against the motion. an endovascular first strategy is not the optimal approach for treating acute mesenteric ischemia. Eur J Vasc Endovasc Surg. 2015;50:276–279. doi: 10.1016/j.ejvs.2015.04.026.
    1. Arthurs ZM, Titus J, Bannazadeh M, Eagleton MJ, Srivastava S, Sarac TP, et al. A comparison of endovascular revascularization with traditional therapy for the treatment of acute mesenteric ischemia. J Vasc Surg. 2011;53:698–705. doi: 10.1016/j.jvs.2010.09.049.
    1. Cocorullo G, Mirabella A, Falco N, Fontana T, Tutino R, Licari L, Salamone G, Scerrino G, Gulotta G. An investigation of bedside laparoscopy in the ICU for cases of non-occlusive mesenteric ischemia. World J Emerg Surg. 2017;12:4. doi: 10.1186/s13017-017-0118-5.
    1. Björck M. Part one: for the motion. an endovascular first strategy is the optimal approach for treating acute mesenteric ischemia. Eur J Vasc Endovasc Surg. 2015;50:273–275. doi: 10.1016/j.ejvs.2015.04.025.
    1. Godat L, Kobayashi L, Costantini T, Coimbra R. Abdominal damage control surgery and reconstruction: world society of emergency surgery position paper. World J Emerg Surg. 2013;8:53. doi: 10.1186/1749-7922-8-53.
    1. Weber DG, Bendinelli C, Balogh ZJ. Damage control surgery for abdominal emergencies. Br J Surg. 2014;101:109–118. doi: 10.1002/bjs.9360.
    1. Subramanian A, Balentine C, Palacio CH, Sansgiry S, Berger DH, Awad SS. Outcomes of damage-control celiotomy in elderly non trauma patients with intra-abdominal catastrophes. Am J Surg. 2010;200:783–788. doi: 10.1016/j.amjsurg.2010.07.027.
    1. Weber DG, Bendinelli C, Balogh ZJ. Damage control surgery for abdominal emergencies. Br J Surg. 2014;101:e109–e118. doi: 10.1002/bjs.9360.
    1. Urbanavičius L, Pattyn P, de Putte DV, Venskutonis D. How to assess intestinal viability during surgery: a review of techniques. World J Gastrointest Surg. 2011;3:59–69. doi: 10.4240/wjgs.v3.i5.59.
    1. Horgan PG, Gorey TF. Operative assessment of intestinal viability. Surg Clin North Am. 1992;72:143–155. doi: 10.1016/S0039-6109(16)45632-X.
    1. Worrell S, Mumtaz S, Tsuboi K, Lee TH, Mittal SK. Anastomotic complications associated with stapled versus hand-sewn anastomosis. J Surg Res. 2010;161:9–12. doi: 10.1016/j.jss.2009.07.004.
    1. Brundage SI, Jurkovich GJ, Hoyt DB, Patel NY, Ross SE, Marburger R, Stoner M, Ivatury RR, Ku J, Rutherford EJ, Maier RV, WTA Multi-institutional Study Group. Western Trauma Association Stapled versus sutured gastrointestinal anastomoses in the trauma patient: a multicenter trial. J Trauma. 2001;51:1054–1061. doi: 10.1097/00005373-200107000-00039.
    1. Smith JW, Matheson PJ, Franklin GA, Harbrecht BG, Richardson JD, Garrison RN. Randomized controlled trial evaluating the efficacy of peritoneal resuscitation in the management of trauma patients undergoing damage control surgery. J Am Coll Surg. 2017;224:396–404. doi: 10.1016/j.jamcollsurg.2016.12.047.
    1. Crafts TD, Hunsberger EB, Jensen AR, Rescorla FJ, Yoder MC, Markel TA. Direct peritoneal resuscitation improves survival and decreases inflammation after intestinal ischemia and reperfusion injury. J Surg Res. 2015;199:428–434. doi: 10.1016/j.jss.2015.06.031.
    1. Acosta S, Björck M, Petersson U. Vacuum-assisted wound closure and mesh-mediated fascial traction for open abdomen therapy—a systematic review. Anaesthesiol Intensive Ther. 2017.[Epub ahead of print].
    1. Hofmann AT, Gruber-Blum S, Lechner M, Petter-Puchner A, Glaser K, Fortelny R. Delayed closure of open abdomen in septic patients treated with negative pressure wound therapy and dynamic fascial suture: the long-term follow-up study. Surg Endosc. 2017. [Epub ahead of print].
    1. Willms A, Schaaf S, Schwab R, Richardsen I, Jänig C, Bieler D, Wagner B, Güsgen C. Intensive care and health outcomes of open abdominal treatment: long-term results of vacuum-assisted wound closure and mesh-mediated fascial traction (VAWCM) Langenbeck’s Arch Surg. 2017;402:481–492. doi: 10.1007/s00423-017-1575-8.
    1. Tolonen M, Mentula P, Sallinen V, Rasilainen S, Bäcklund M, Leppäniemi A. Open abdomen with vacuum-assisted wound closure and mesh-mediated fascial traction in tients with complicated diffuse secondary peritonitis: A single-center 8-year experience. J Trauma Acute Care Surg. 2017;82:1100–1105. doi: 10.1097/TA.0000000000001452.
    1. Acosta S. Surgical management of peritonitis secondary to acute superior mesenteric artery occlusion. World J Gastroenterol. 2014;20:9936–9941. doi: 10.3748/wjg.v20.i29.9936.
    1. Hmoud B, Singal AK, Kamath PS. Mesenteric venous thrombosis. J Clin Exp Hepatol. 2014;4:257–263. doi: 10.1016/j.jceh.2014.03.052.
    1. al Karawi MA, Quaiz M, Clark D, Hilali A, Mohamed AE, Jawdat M. Mesenteric vein thrombosis, non-invasive diagnosis and follow-up (US + MRI), and non-invasive therapy by streptokinase and anticoagulants. Hepato-Gastroenterology. 1990;37:507–509.
    1. Semiz-Oysu A, Keussen I, Cwikiel W. Interventional radiological management of prehepatic obstruction of [corrected] the splanchnic venous system. Cardiovasc Intervent Radiol. 2007;30:688–695. doi: 10.1007/s00270-007-9097-3.
    1. Sehgal M, Haskal ZJ. Use of transjugular intrahepatic portosystemic shunts during lytic therapy of extensive portal splenic and mesenteric venous thrombosis: long-term follow-up. J Vasc Interv Radiol. 2000;11:61–65. doi: 10.1016/S1051-0443(07)61283-4.
    1. Meilahn JE, Morris JB, Ceppa EP, Bulkley GB. Effect of prolonged selective intramesenteric arterial vasodilator therapy on intestinal viability after acute segmental mesenteric vascular occlusion. Ann Surg. 2001;234:107–115. doi: 10.1097/00000658-200107000-00016.
    1. Lilley EJ, Cooper Z, Schwarze ML, Mosenthal AC. Palliative care in surgery: defining the research priorities. J Palliat Med. 2017;20:702–709. doi: 10.1089/jpm.2017.0079.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe