Red Blood Cell Distribution Width as a Risk Factor for 30/90-Day Mortality in Patients with Gastrointestinal Bleeding: Analysis of the MIMIC-IV Database.

PURPOSE: The purpose of this research was to assess the relationship between red blood cell distribution width (RDW) and mortality in patients with gastrointestinal (GIB) bleeding in the intensive care unit (ICU). METHODS: The information of the participants was obtained from the Medical Information Mart for Intensive Care IV database. The main outcome of this research was 30/90-day mortality, with ICU mortality and in-hospital mortality as secondary outcomes. RESULTS: This research included 2924 patients with gastrointestinal bleeding in total. Patients with higher RDW had considerably higher 30/90-day and in-hospital mortality rates, as well as longer hospital stays and ICU stays. According to the Kaplan-Meier analysis, the 30/90-day mortality rate was remarkably higher among participants in the higher RDW group (P < 0.0001). In the adjusted multivariate Cox regression analysis, for 30-day mortality, the HR (95% CI) was 1.75 (1.37, 2.24) in comparison to Q1 in the reference group (P < 0.001). Analyses of 90-day mortality and in-hospital mortality both showed the same results. In the subgroup analysis, gender, myocardial infarction, chronic pulmonary disease, cerebrovascular disease and renal disease had no significant effect on the correlation between RDW values and mortality (all P > 0.05). The area under the ROC curve for RDW was 0.599 (95% CI 0.581-0.617) and 0.606 (95% CI 0.588-0.624) in 30/90-day ICU mortality. CONCLUSION: The current research showed that RDW could be utilized as an independent indicator of short-term mortality in critically ill GIB patients at 30 and 90 days of hospital admission.

Untimely surgery for stent-fracture-related death after transjugular intrahepatic portosystemic shunt: a case report.

Transjugular intrahepatic portosystemic shunt (TIPS) is a life-saving procedure for patients with severe portal hypertension and persistent variceal bleeding. Stent fracture is a rare and severe complication; however, its cause and mechanisms remain poorly defined. This case helps understand the factors contributing to its occurrence, complications, and subsequent poor outcomes. A 63-year-old male was presented with ruptured bare stent after a TIPS procedure. The upper edge of the bare stent was ruptured, and its fraction subsequently migrated to the entrance of the right atrium. Meanwhile, a mural thrombus was formed in the inferior vena cava. A surgery for the removal of free fracture was planned for preventing the form of pulmonary embolism. Before the surgery, the fracture was shifted to the right inferior pulmonary artery. Therefore, the surgery was canceled for further evaluation. Then, hematemesis suddenly occurred with a high possibility of variceal bleeding and/or gastric ulcer bleeding. Despite comprehensive treatments, the patient symptoms were still worsened with the development of chest tightness, shortness of breath, severe hypoxia, and heart failure. Finally, the patient succumbed to systemic multiorgan failure and death. Taken together, a ruptured unstable stent should be removed as early as the patient is hemodynamically stable, as it is difficult to balance between hemostasis therapy and anticoagulation treatment in patients with liver-cirrhosis-related severe portal hypertension. Physicians should be on high alert of the potential complications of bare stent rapture after TIPS.

Ruptured TIPS stent with a fatal consequence Unstable stent rupture is a life-threatening complication of TIPS and severely complicates the treatment of gastric ulcer bleeding. Early removal of the ruptured stent is necessary to prevent further complications.

Duodenocaval Fistula: Unmasking the Rare Culprit of Gastrointestinal Hemorrhage.

Duodenocaval fistula is an extremely rare and life-threatening cause of gastrointestinal hemorrhage and septicemia. Diagnosing this condition is challenging due to its nonspecific symptoms, leading to significant delays in diagnosis and contributing to its remarkably high mortality rate. We present a unique case of duodenocaval fistula associated with prior radiation, peptic ulcer disease, and antiangiogenic cancer therapy, nearly resulting in the death of a young patient.

Intravenous metoclopramide for increasing endoscopic mucosal visualization in patients with acute upper gastrointestinal bleeding: a multicenter, randomized, double-blind, controlled trial.

Acute upper gastrointestinal hemorrhage (UGIH) is the most common emergency condition that requires rapid endoscopic treatment. This study aimed to evaluate the effects of pre-endoscopic intravenous metoclopramide on endoscopic mucosal visualization (EMV) in patients with acute UGIH. This was a multicenter, randomized, double-blind controlled trial of participants diagnosed with acute UGIH. All participants underwent esophagogastroduodenoscopy within 24 h. Participants were assigned to either the metoclopramide or placebo group. Modified Avgerinos scores were evaluated during endoscopy. In total, 284 out of 300 patients completed the per-protocol procedure. The mean age was 62.8 ± 14.3 years, and 67.6% were men. Metoclopramide group achieved a higher total EMV and gastric body EMV score than the other group (7.34 ± 1.1 vs 6.94 ± 1.6; P = 0.017 and 1.80 ± 0.4 vs 1.64 ± 0.6; P = 0.006, respectively). Success in identifying lesions was not different between the groups (96.5% in metoclopramide and 93.6% in placebo group; P = 0.26). In the metoclopramide group, those with active variceal bleeding compared with the control group demonstrated substantial improvements in gastric EMV (1.83 ± 0.4 vs 1.28 ± 0.8, P = 0.004), antral EMV (1.96 ± 0.2 vs 1.56 ± 0.6, P = 0.003), and total EMV score (7.48 ± 1.1 vs 6.2 ± 2.3, P = 0.02). Pre-endoscopic intravenous metoclopramide improved the quality of EMV in variceal etiologies of UGIH, which was especially prominent in those who had signs of active bleeding based on nasogastric tube assessment.Trial Registration: Trial was registered in Clinical Trials: TCTR 20210708004 (08/07/2021).

Multiple Ulcers in the Ileum and Lymphadenopathy Following the Usage of Methotrexate in a Patient With Rheumatoid Arthritis: A Case Report.

This case report aims to highlight a rare occurrence of severe anemia and lymphadenopathy secondary to methotrexate (MTX)-induced ileal mucosa damage in a patient with elderly onset rheumatoid arthritis (EORA). We present the case of a 72-year-old female with a history of EORA, treated with MTX, who exhibited hematochezia without accompanying pain, diarrhea, or known infectious contacts. Diagnostic investigations included imaging and endoscopic procedures. The patient's presentation of severe anemia was atypical, given the absence of significant pain or discomfort associated with EORA. The lack of active bleeding observed during endoscopy, coupled with multiple ileal ulcers, suggested a chronic progression of mucosal damage. Laboratory findings, including normal lactate dehydrogenase, soluble interleukin-2 receptor levels, and the absence of malignancy in mucosal biopsies, ruled out MTX-induced lymphoma. The patient's condition improved with the cessation of MTX and the introduction of symptomatic treatment and anemia management. This case underscores the need for vigilant monitoring and comprehensive evaluation in patients with RA, especially the elderly, treated with MTX. It also highlights the importance of considering drug-induced complications in the differential diagnosis of anemia. The case demonstrates the necessity of a personalized approach to treatment, emphasizing regular follow-ups and adjustments based on the patient's response to therapy. This report contributes to the growing body of evidence on the complexities of managing RA in the elderly, particularly regarding the side effects of common medications like MTX.

Gastrointestinal Bleeding in Patients With Acute Ischemic Stroke: A Literature Review.

Stroke is an infarction of the central nervous system (brain, spinal cord, or retina) that results from a disruption in cerebral blood flow either due to ischemia or hemorrhage. Complications of acute stroke are common and include pneumonia, urinary tract infection, myocardial infarction, deep vein thrombosis, and pulmonary embolism, among several others, all of which increase the risk of poor clinical outcomes. Gastrointestinal bleeding is a well-known complication that can occur during the acute phase of stroke. In this review, we have summarized the existing data regarding the incidence, pathophysiology, risk factors, morbidity, mortality, and management strategies for gastrointestinal bleeding in patients with acute ischemic stroke.

Managing Patients With Concurrent High Risk for Bleeding and Thromboembolic Events.

The number of patients with high bleeding risk (HBR) and high thromboembolic risk (HTR) is increasing. Gastrointestinal bleeding (GIH), acute coronary syndrome (ACS), and pulmonary embolism (PE) are representative conditions due to HBR/HTR. Although these disorders are located at opposite ends of the same disease spectrum, this does not mean a patient with HBR cannot have a concomitant HTR. The clinical manifestation of these two risks mostly results in critically ill patients for whom management means a huge challenge. We have numerous well-structured guidelines about treating GIH, ACS, or PE, but the literature and recommendations about the concomitant onset of these diseases are limited. Expert recommendations suggest an integrative, comprehensive assessment of patient and intervention-related factors to decide on the antithrombotic regimen with the best clinical benefit by assessing thrombotic and bleeding risks. In general, if thrombotic factors predominate, a longer duration, more aggressive antithrombotic regimen should be planned, and if bleeding susceptibility is higher, a shorter duration, de-escalated regimen should be pursued. In this study, we aimed to explore the clinical dilemmas involved by presenting two cases with delicate management.

Current status and clinical outcome of endoscopic hemostatic powder in gastrointestinal bleeding: a retrospective multicenter study.

Background/Aims: Few multicenter studies have investigated the efficacy of hemostatic powders in gastrointestinal (GI) bleeding. We aimed to investigate the clinical outcomes of hemostatic powder therapy and the independent factors affecting rebleeding rates. Methods: We retrospectively recruited patients who underwent a new hemostatic adhesive powder (UI-EWD; Next-Biomedical) treatment for upper and lower GI bleeding between January 1, 2020 and March 1, 2023. We collected patients' medical records and bleeding lesions. The primary outcomes were clinical and technical success rates, and the secondary outcomes were early, delayed, and refractory bleeding, mortality, and factors affecting early rebleeding rates. Results: This study enrolled 135 patients (age: 67.7±13.6 years, male: 74.1%) from five hospitals. Indications for UI-EWD were peptic ulcers (51.1%), post-procedure-related bleeding (23.0%), and tumor bleeding (19.3%). The clinical and technical success rates were both 97%. The early, delayed, and refractory rebleeding rates were 19.3%, 11.1%, and 12.8%, respectively. Initially elevated blood urea nitrogen (BUN) levels (p=0.014) and Forrest classification IA or IB compared with IIA or IIB (p=0.036) were factors affecting early rebleeding. Conclusions: UI-EWD showed high clinical and technical success rates; however, rebleeding after UI-EWD therapy in patients with initially high BUN levels and active bleeding, according to the Forrest classification, should be considered.

Hepatic Portal Venous Gas Associated with Acute Upper Gastrointestinal Hemorrhage: A Case Report and Literature Review.

BACKGROUND: Hepatic portal venous gas (HPVG) is very rare; it is associated with multiple gastrointestinal etiologies, with pathophysiology not yet fully understood. It is characteristically fast-progressing and has a high mortality rate. Treatment choice depends on the etiology, including conservative and surgical management. CASE PRESENTATION: We report an adult patient (less than 25 years old) of HPVG combined with acute upper gastrointestinal hemorrhage, in which massive gas in the hepatic portal vein system by computed tomography of the abdomen was rapidly dissipated by nasogastric decompression conservative management. CONCLUSION: Nasogastric decompression can be an effective treatment approach for HPVG when timely surgical treatment is not required.

Endoscopic Diagnosis, Grading, and Treatment of Bleeding Peptic Ulcer Disease.

Peptic ulcer bleeding is a major cause for hospital admissions and has a significant mortality. Endoscopic interventions reduce the risk of rebleeding in high-risk patients and several options are available including injection therapies, thermal therapies, mechanical clips, hemostatic sprays, and endoscopic suturing. Proton-pump inhibitors and Helicobacter pylori treatment are important adjuncts to endoscopic therapy. Endoscopic therapy is indicated in Forrest 1a, 1b, and 2a lesions. Patients with Forrest 2b lesions may do well with proton-pump inhibitor therapy alone but can also be managed by removal of the clot and targeting endoscopic therapy to the underlying lesion.

Intestinal tuberculosis with small bowel stricture and hemorrhage as the predominant manifestation: Three case reports.

BACKGROUND: Intestinal tuberculosis is a chronic disease caused by Mycobacterium tuberculosis that mainly affects the ileum and cecum. Small bowel tuberculosis, characterized by predominant involvement of the small intestine, is an extremely rare condition with highly atypical clinical presentations, making diagnosis even more challenging. CASE SUMMARY: We report three cases of small intestinal tuberculosis, two of the patients presented primarily with abdominal pain, and one presented with gastrointestinal bleeding. All patients underwent blood tests and imaging examinations. Small bowel endoscopy (SBE) revealed that the main lesions in these patients were intestinal stenosis or gastrointestinal bleeding caused by small intestinal ulcers. One patient ultimately underwent surgical treatment. Following a complex diagnostic process and comprehensive analysis, all patients were confirmed to have small intestinal tuberculosis and received standard antituberculosis treatment, leading to an improvement in their condition. CONCLUSION: Patients with SBTs present with nonspecific symptoms such as abdominal pain, weight loss, and occasional gastrointestinal bleeding. Accurate diagnosis requires a thorough evaluation of clinical symptoms and various tests to avoid misdiagnosis and complications.

Real-World Risk of Gastrointestinal Bleeding for Direct Oral Anticoagulants and Warfarin Users: A Distributed Network Analysis Using a Common Data Model.

Background/Aims: : Early studies on direct oral anticoagulants (DOACs) reported a higher risk of gastrointestinal bleeding (GIB) compared with warfarin; however, recent studies have reported a reduced risk. Therefore, this study was designed to evaluate the risk of GIB in users of DOAC and warfarin. Methods: : Using a common data model, we investigated the comparative risk of GIB in subjects from eight hospitals who were newly prescribed DOACs or warfarin. We excluded subjects who had a prior history of GIB or had been prescribed both medications. After propensity score matching, we analyzed 3,347 matched pairs of new DOAC and new warfarin users. Results: : The risk of GIB in new DOAC users was comparable to that in new warfarin users (hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.65 to 1.40; p=0.808). New DOAC users had a similar risk of GIB to new warfarin users among older patients >65 years (HR, 1.00; 95% CI, 0.69 to 1.52; p=0.997) and in older patients >75 years (HR, 1.21; 95% CI, 0.68 to 2.10; p=0.509). In addition, the risk of GIB was not significantly different between two groups according to sex. We also found that the risk of GIB in DOAC users was 26% lower in edoxaban or apixaban subgroups compared to rivaroxaban or dabigatran subgroups (HR, 0.74; 95% CI, 0.69 to 1.00; p=0.049). Conclusions: : In real-world practice, the risk of GIB in new DOAC users is comparable to that in new warfarin users. In DOAC users, the risk of GIB was lower in edoxaban or apixaban subgroups than rivaroxaban or dabigatran subgroups.

Pantoprazole and Vonoprazan Performed Well in Preventing Peptic Ulcer Recurrence in Low-Dose Aspirin Users.

BACKGROUND: Low-dose aspirin (LDA) administration is associated with an elevated risk of recurring peptic ulcer (PU) and gastrointestinal (GI) hemorrhage. AIMS: This systematic review and Bayesian network meta-analysis aimed to comprehensively assess the effectiveness of diverse medications in preventing the recurrence of PU and GI hemorrhage in patients with a history of PU receiving long-term LDA therapy. METHODS: This systematic review and network meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and was registered on PROSPERO (CRD42023406550). We searched relevant studies in main databases from inception to March 2023. All statistical analyses were performed using R (version 4.1.3), with the "Gemtc" (version 1.0-1) package. The pooled risk ratio (RR), corresponding 95% credible interval (95% CrI), and the surface under the cumulative ranking curve (SUCRA) were calculated. RESULTS: 11 Randomized clinical trials (RCTs) were included. The analysis underscored pantoprazole was the most efficacious for reducing the risk of PU recurrence (RR [95% CrI] = 0.02 [0, 0.28]; SUCRA: 90.76%), followed by vonoprazan (RR [95% CrI] = 0.03 [0, 0.19]; SUCRA: 86.47%), comparing with the placebo group. Pantoprazole also performed well in preventing GI hemorrhage (RR [95% CrI] = 0.01[0, 0.42]; SUCRA: 87.12%) compared with Teprenone. CONCLUSIONS: For patients with a history of PU receiving LDA, pantoprazole and vonoprazan might be the optimal choices to prevent PU recurrence and GI hemorrhage.

Risk factors for massive gastrointestinal bleeding occurrence and mortality: A prospective single-center study.

BACKGROUND: Massive gastrointestinal bleeding is a life-threatening condition without a well-established definition. We aimed to analyze the characteristics, risk factors, and outcomes of patients with massive upper gastrointestinal bleeding. METHODS: Our study analyzed a prospective registry of patients admitted between 2013 and 2020 with variceal and non-variceal causes. Severe bleeding was defined as ongoing bleeding requiring transfusion of more than 2 units of packed red blood cells within 24 hours, accompanied by signs of shock. The main outcomes were 30-day and 6-month mortality, rebleeding within 7 days, persistent bleeding, and severe complications during admission. RESULTS: Out of 1213 patients, 171 had massive gastrointestinal bleeding, with a predominance of males. The massive bleeding group had higher rates of chronic kidney disease, cirrhosis, in-patient status, disseminated malignancy, alcoholism, and ASA score ≥3. All major outcomes, including 30-day mortality, 6-month mortality, rebleeding, persistent bleeding, and severe complications, were more common in the massive bleeding group. Multivariate logistic regression identified inpatient status, systemic diseases, malignancy, active bleeding in endoscopy, and severe complications as risk factors for massive bleeding and mortality. CONCLUSIONS: Inpatient status and comorbidities, especially systemic diseases, and malignancies, were associated with a higher risk of massive bleeding. Mortality was linked to chronic kidney disease, cirrhosis, severe comorbidities, and alcohol consumption. We observed increased 6-months mortality, probably related to a health status in which gastrointestinal bleeding heralded poor outcomes, some of them potentially preventable. Innovative healthcare interventions, such as Emergency Department-based intermediate care areas or Intensive Care Units, and multidisciplinary follow-up, could potentially improve survival.

Novel upper gastrointestinal bleeding sensor capsule: a first human feasibility and safety trial.

BACKGROUND/AIMS: Upper gastrointestinal bleeding (UGIB) is the most common GI condition requiring hospitalization, and can be diagnosed by direct visualization. The present study aimed to evaluate the safety and feasibility of using the PillSense system (EnteraSense Ltd.), a novel diagnostic tool designed for the rapid in vivo detection of UGIB, in human volunteers. METHODS: In the present study, 10 volunteers swallowed a PillSense capsule, followed by 2 servings of an autologous blood preparation. Participants were monitored for capsule passage, overall tolerability of the procedure, and adverse events. RESULTS: The procedure was completed per the protocol established in the present study in 9/10 cases. In 9 of the subjects, after capsule ingestion, the device indicated the absence of blood with sensor output values of 1. After the ingestion of the first blood mixture, the sensor outputs of all devices increased from 2.8 to 4, indicating that each camera detected blood. The sensor output remained within that range after the ingestion of the second mixture; however, in one case, the baseline capsule signal was positive, because of a preexisting condition. The passage of the capsule was verified in all patients, and no adverse events were reported. CONCLUSION: The first trial of the PillSense system in human subjects demonstrated the feasibility, safety, and tolerability of utilizing this product as a novel, noninvasive, and easy-to-use triage tool for the diagnosis of patients suspected of having UGIB.

Varicose vein embolization and portal vein stenting in a patient with sinistral portal hypertension-induced gastrointestinal hemorrhage: a case report.

Introduction and importance: Massive gastrointestinal hemorrhage is a severe hemorrhage that occurs in the gastrointestinal tract and is a life-threatening condition. Sinistral portal hypertension is a common etiology for massive gastrointestinal hemorrhage, whose occurrence might be derived from pathological changes induced by obstruction and/or increased blood flow to the portal vein system. However, there is a rare study reporting pancreatic disease-induced sinistral portal hypertension. Case presentation: An 80-year-old female pancreatic cancer patient was admitted to our hospital on 22 January 2022 due to a massive gastrointestinal hemorrhage with shock after receiving radio-chemotherapy. Abdominal enhanced computerized tomography showed that the patient presented with pancreatic cancer-causing sinistral portal hypertension with massive collateral circulation, intrahepatic bile duct dilation, and the formation of massive ascites. Subsequent portography interventional procedure revealed the esophageal and gastric varix. Then, the varicose vein was embolized, and the stent was implanted at the lumen of the superior mesenteric vein accessing the portal vein. The patient recovered from pancreatic cancer-causing sinistral portal hypertension, and a normal direction of blood flow was observed in the superior mesenteric vein with a decreasing amount of ascites. In addition, a transfusion was also carried out, and the massive gastrointestinal hemorrhage was alleviated. Clinical discussion and conclusion: This study emphasizes the successful treatment of massive gastrointestinal hemorrhage induced by pancreatic cancer-causing sinistral portal hypertension by varicose vein embolization and portal vein stenting, which could be considered an alternative opinion for these patients.

Gastrointestinal metastases in renal cell carcinoma: A retrospective multicenter GETUG (Groupe d'Étude des Tumeurs Uro-Génitales) study.

BACKGROUND: Among patients with renal cell carcinoma (RCC), bone and visceral metastases have a poor prognosis, while endocrine gland metastases have a more favorable prognosis. Gastrointestinal metastases (GIMs) are rare, and their prognosis is still poorly understood. OBJECTIVES: To report clinical presentations, patient characteristics, therapeutic strategies, and prognosis of GIMs from RCC. METHODS: We retrospectively collected data from RCC patients presenting GIMs, in 10 French GETUG centers, between 2000 and 2021. RESULTS: We identified 74 patients with 87 GIMs, mostly gastric or duodenal. The median age at GIM diagnosis was 69 years and 76% of patients already had other metastases. GIMs occurred after a median duration of 5.4 years (IC95%=[4.2-7.1]) and 1.9 years (IC95%=[1.2-3.8]) from RCC diagnosis and first metastasis, respectively. GIMs were symptomatic in 52 patients (70%), with anemia in 41 patients (55%) and/or gastrointestinal bleeding in 31 patients (42%). Only 22 asymptomatic patients (30%) were fortuitously diagnosed. GIM management consisted of systemic treatment only in 29 GIMs (33%), local treatment only in 23 GIMs (26%), and both local and systemic treatment in 18 GIMs (21%). For 17 GIMs (20%), there was no therapeutic modification. After diagnosis of GIM, median overall survival was 19 months. CONCLUSION: We report the largest retrospective cohort of GIMs in RCC patients. They should be suspected in case of anemia or gastrointestinal bleeding in any patient with a history of RCC. Their management varies widely depending on their location in the digestive tract and whether or not they are symptomatic.

[Recurrent Bacteremia after Cyanoacrylate Sclerotherapy of Ectopic Duodenal Varices]. / Bacteriemias Recorrentes após Escleroterapia de Varizes Ectópicas Duodenais com Cianoacrilato.

Sclerotherapy with N-butyl-2-cyanoacrylate is the first-line endoscopic approach for gastric and ectopic variceal bleeding, but it can be associated with local or systemic complications. Episodes of transient bacteremia after the procedure are frequent, but documented cases of recurrent bacteremia are rare. The authors report a 47-year-old female patient with liver cirrhosis who underwent duodenal sclerotherapy with cyanoacrylate after upper gastrointestinal bleeding. Subsequently, she developed five episodes of bacteremia with unknown origin. A definitive diagnosis of recurrent bacteremia due to cyanoacrylate was only possible after an exhaustive study to exclude other infectious foci. This case highlights a rare complication in an unusual topography (ectopic varices) and with a high number of episodes of bacteremia. A multidisciplinary management was paramount due to the patient's high surgical and anesthetic risk, comorbidities, and surgical aggressiveness.

A escleroterapia com N-butil-2-cianoacrilato é a abordagem endoscópica de primeira linha nas hemorragias por varizes gástricas ou ectópicas, podendo estar associada a complicações locais ou sistémicas. São frequentes situações de bacteriemia transitória após o procedimento, mas são raros os casos documentados de bacteriemias recorrentes. O caso relata uma doente de 47 anos com cirrose hepática submetida a esclerose de varizes duodenais com cianoacrilato após hemorragia digestiva alta. Posteriormente, desenvolveu cinco episódios de bacteriémia sem foco evidente. O diagnóstico definitivo de bacteriemias recorrentes com ponto de partida no cianoacrilato só foi possível após estudo exaustivo para excluir outros focos infeciosos. Este caso evidencia uma complicação rara, numa topografia também incomum (varizes ectópicas) e com um elevado número de episódios de bacteriémia. Destaca-se a importância de uma abordagem multidisciplinar para gerir esta doente, tendo em conta as comorbilidades, o elevado risco anestésico e a agressividade cirúrgica para extração do foco infecioso.