Establishment of a swine model of delayed bleeding after endoscopic procedure.

Objectives: Although delayed bleeding after endoscopic procedures has become a problem, currently, there are no appropriate animal models to validate methods for preventing it. This study aimed to establish an animal model of delayed bleeding after endoscopic procedures of the gastrointestinal tract. Methods: Activated coagulation time (ACT) was measured using blood samples drawn from a catheter inserted into the external jugular vein of swine (n = 7; age, 6 months; mean weight, 13.8 kg) under general anesthesia using the cut-down method. An upper gastrointestinal endoscope was inserted orally, and 12 mucosal defects were created in the stomach by endoscopic mucosal resection using a ligating device. Hemostasis was confirmed at this time point. The heparin group (n = 4) received 50 units/kg of unfractionated heparin via a catheter; after confirming that the ACT was ≥200 s 10 min later, continuous heparin administration (50 units/kg/h) was started. After 24 h, an endoscope was inserted under general anesthesia to evaluate the blood volume in the stomach and the degree of blood adherence at the site of the mucosal defect. Results: Delayed bleeding was observed in three swine (75%) in the heparin-treated group, who had a maximum ACT of >220 s before the start of continuous heparin administration. In the non-treated group (n = 3), no prolonged ACT or delayed bleeding was observed at 24 h. Conclusion: An animal model of delayed bleeding after an endoscopic procedure in the gastrointestinal tract was established using a single dose of heparin and continuous heparin administration after confirming an ACT of 220 s.

Appendicitis after endoscopic band ligation for massive ileocecal hemorrhage.

A 68-year-old man was admitted with hematochezia. Emergency computed tomography showed multiple diverticula throughout the colon. Initial colonoscopy on day 2 showed no active bleeding, but massive hematochezia on day 3 led to the performance of an emergency endoscopy. Substantial bleeding in the ileocecal area obscured the visual field, making it challenging to view the area around the bleeding site. Two endoscopic band ligations (EBLs) were applied at the suspected bleeding sites. Hemostasis was achieved without active bleeding after EBL. However, the patient developed lower right abdominal pain and fever (39.4°C) on day 6. Urgent computed tomography revealed appendiceal inflammation, necessitating emergency open ileocecal resection for acute appendicitis. Pathological examination confirmed acute phlegmonous appendicitis, with EBLs noted at the appendiceal orifice and on the anal side. This case illustrates the efficacy of EBL in managing colonic diverticular bleeding. However, it also highlights the risk of appendicitis due to EBL in cases of ileocecal hemorrhage exacerbated by poor visibility due to substantial bleeding. Endoscopists need to consider this rare but important complication when performing EBL in similar situations.

Clinical usefulness and acceptability of small-bowel capsule endoscopy with panoramic imaging compared with axial imaging in Japanese patients.

Objectives: We aimed to evaluate the usefulness and acceptability of CapsoCam Plus (CapsoCam) in Japanese patients. Methods: This retrospective single-center study enrolled 930 patients with suspected small-bowel bleeding (SSBB) who underwent capsule endoscopy. Thirty-three patients using CapsoCam and PillCam SB3 (SB3) were matched using propensity score matching. The diagnostic yield and the acceptability of CapsoCam were evaluated. Results: There was no SSBB case where capsule endoscopy was performed within 48 h of bleeding. CapsoCam had a significantly higher observation rate of the entire small bowel (97% vs. 73%, p = 0.006) and Vater's papilla (82% vs. 15%, p < 0.001) than SB3. The reading time of CapsoCam was significantly longer than that of SB3 (30 vs. 25 min, p < 0.001), and CapsoCam's time from the capsule endoscopy swallowing to read completion was longer than that of SB3 (37 vs. 12 h, p < 0.001). The two groups showed no difference in the capsule endoscopy findings according to the P classification. Notably, 85% of the patients using CapsoCam reported examination distress as "not at all" or "almost not," and 94% reported swallowing difficulty as "very easy" or "easy." Conclusions: CapsoCam took time to read; however, it is a well-tolerated examination with a high observation rate of Vater's papilla and entire small-bowel mucosa. Detectability of bleeding sources was comparable in both modalities for cases of occult SSBB and overt SSBB more than 48 h after bleeding. CapsoCam is a useful modality for patients with SSBB.

PGE2 Regulates the Plasminogen Activator Pathway in Human Endometrial Endothelial Cells: A New In Vitro Model to Investigate Heavy Menstrual Bleeding.

OBJECTIVE: To study the role of PGE2 in regulating plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA) in human primary endometrial endothelial cells (HEECs) from women with normal menstrual bleeding (NMB) and heavy menstrual bleeding (HMB). DESIGN: In vitro study using endometrial endothelial cells. SETTING: Research laboratory setting. PATIENTS: Women with normal menstrual bleeding (NMB) and heavy menstrual bleeding (HMB) provided endometrial biopsy samples. INTERVENTIONS: PGE2 and PGE2 receptor-selective agonists were administered to cultured HEECs. MAIN OUTCOME MEASURES: Levels of PAI-1 and tPA in NMB-HEECs and HMB-HEECs after treatment with PGE2 and receptor-selective agonists. RESULTS: PGE2 increased total PAI-1 levels in NMB-HEECs, but not in HMB-HEECs, which had higher baseline PAI-1 levels. PTGER1 and PTGER2 agonists increased PAI-1 in NMB-HEECs, while PTGER3 and PTGER4 did not. PGE2 had no effect on tPA levels in either NMB-HEECs or HMB-HEECs. CONCLUSIONS: PGE2, through PTGER1 and PTGER2, regulates the plasminogen activator system in NMB-HEECs, suggesting a role in reducing fibrinolytic activity during normal menstrual cycles. The lack of PGE2 effect and elevated baseline PAI-1 in HMB-HEECs support using this in vitro model to further understand prostaglandin pathways in normal and heavy menstrual bleeding.

Deaths and major cardiovascular events in patients with lymphoma: Analysis from a French nationwide hospitalization database.

BACKGROUND: There are few data assessing the risk of death and cardiovascular events in patients with lymphoma. AIM: Using a nationwide hospitalization database, we aimed to address cardiovascular outcomes in patients with lymphoma. METHODS: From 01 January to 31 December 2013, 3,381,472 adults were hospitalized in French hospitals; 22,544 of these patients had a lymphoma. The outcome analysis (all-cause or cardiovascular death, myocardial infarction, ischaemic stroke, bleedings, new-onset heart failure and new-onset atrial fibrillation) was performed over a 5-year follow-up period. Each patient with lymphoma was matched with a patient without a lymphoma or other cancer (1:1). A competing risk analysis was also performed. RESULTS: After adjustment on all risk factors, cardiovascular and non-cardiovascular co-morbidities, the subdistribution hazard ratios for all-cause death, major bleeding, intracranial bleeding, new-onset heart failure and new-onset atrial fibrillation were higher in patients with lymphoma; conversely, the subdistribution hazard ratios for cardiovascular death, myocardial infarction and ischaemic stroke were lower in patients with lymphoma. In the matched analysis, the risk of all-cause death (subdistribution hazard ratio 1.936, 95% confidence interval 1.881-1.992) and major bleeding (subdistribution hazard ratio 1.117, 95% confidence interval 1.049-1.188) remained higher in patients with lymphoma. CONCLUSION: In this large nationwide cohort study, patients with lymphoma had a higher incidence of all-cause death and major bleeding.

Patients with atrial fibrillation and common exclusion criteria from clinical trials are at high risk of clinical events: the Murcia AF Project II (MAFP-II) cohort study.

BACKGROUND: Some clinical characteristics and comorbidities in atrial fibrillation (AF) patients are exclusion criteria in randomized clinical trials (RCTs) investigating oral anticoagulants (OAC). However, these conditions are present also in everyday clinical practice patients. We compared the risk of adverse clinical outcomes between patients with and without RCT exclusion criteria. METHODS: The Murcia AF Project II was an observational cohort study including AF outpatients starting vitamin K antagonists (VKAs) from July 2016 to June 2018. For the selection of the exclusion criteria, the four pivotal RCTs of direct-acting OAC (DOACs) were used as reference. During 2 years, all ischemic strokes/transient ischemic attacks, major adverse cardiovascular events (MACEs), major bleeds, and all-cause deaths were recorded. RESULTS: 1050 patients (51.5% female, median age 77 years) were included, of whom 368 (35%) met at least one exclusion criterion for RCTs. During follow-up, the incidence rate ratios for major bleeding, MACE and all-cause mortality were higher among patients with exclusion criteria (all p < 0.001). Patients fulfilling at least one exclusion criterion had increased risks of major bleeding (aHR 1.48; 95% CI 1.22-1.81; p < 0.001), MACE (aHR 1.51, 95% CI 1.10-2.09, p = 0.012), and mortality (aHR 3.22, 95% CI 2.32-4.48, p < 0.001), as well as a lower event-free survival (all log-rank p < 0.001). CONCLUSIONS: In this AF cohort taking VKAs, more than one-third had at least one RCT exclusion criteria, which translates into higher risk of major bleeding, MACE, and death. These observations should be considered when translating RCTs results to AF patients for a proper and a more patient-centered management.

Clinical outcomes of endoscopic detachable snare ligation for colonic diverticular hemorrhage: Multicenter cohort study.

OBJECTIVES: The hemostatic mechanism of endoscopic detachable snare ligation (EDSL) for colonic diverticular hemorrhage (CDH) is similar to that of endoscopic band ligation, which is effective and safe. However, because reports on EDSL are scarce, we conducted a two-center cohort study to evaluate its effectiveness. METHODS: This study analyzed 283 patients with CDH treated with EDSL at two Japanese hospitals between July 2015 and November 2021. Patient characteristics and clinical outcomes were retrospectively evaluated. A Kaplan-Meier analysis was performed to evaluate the cumulative probability of rebleeding after EDSL. A Cox proportional hazards regression analysis was performed to compare the effects of complete and incomplete ligation on rebleeding. RESULTS: The initial hemostasis success and early rebleeding rates were 97.9% and 11.0%, respectively. The time to hemostasis after identification of the bleeding site and total procedure time were 9 min and 44 min, respectively. Red blood cell transfusion was required for 32.9% of patients. The median hospital length of stay after EDSL was 5 days. The complete ligation rate of the early rebleeding group was significantly lower than that of the group without early rebleeding (P < 0.01). The 1-year cumulative rebleeding rate with EDSL was 28.2%. Complete ligation was associated with decreased cumulative rebleeding after EDSL (P < 0.01). One patient experienced colonic diverticulitis; however, colonic perforation was not observed. CONCLUSION: Complete ligation is associated with reduced short-term and long-term rebleeding. EDSL could be valuable for CDH because of its low rebleeding rate and the absence of serious adverse events.

Patient Weight and Chemoprophylaxis in Abdominoplasty: Does It Result in More Bleeding Events?

BACKGROUND: Bariatric surgery has gained popularity in recent decades as an effective treatment for obesity. Abdominoplasty is one of the most often performed aesthetic procedures all over the world. In post-bariatric patients undergoing abdominoplasty, the diameter size and number of the abdominal wall perforators increase proportionally with increased body weight. Postoperative complications that may occur are haematoma, and venous thromboembolism (VTE). In plastic surgery procedures VTE prophylaxis grades vary due to the lack of consensus and clear guidelines. The aim of this study was to explore the frequency of postoperative bleeding and VTE in patients undergoing abdominoplasty and to explore the risk factors associated with major bleeding. METHODS: A retrospective single-centre study of adult patients who were operated on by abdominoplasty between 2011 and 2020. Chemoprophylaxis including low molecular weight heparin (LMHW) was recommended when the operating time exceeded 2 h. RESULTS: A total of 102 patients were included. There were no patients with VTE. Eight patients were re-operated for major haematoma. The weight loss (peak weight to weight before the abdominoplasty) was 14.4 kg larger in the re-operation group (p = 0.03). Eighty-eight percent in the re-operation group and 67% in the other group were treated with LMWH (p = 0.43). Multivariable logistic regression showed that with each decrease from the peak in BMI kg/m2 the risk of re-operation for major haematoma was increased by 22% (p = 0.02). CONCLUSION: Abdominoplasty in patients after massive weight loss has a higher risk of postoperative bleeding. Having a clear protocol for chemoprophylaxis should be considered. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Clinical outcomes of patients with atrial fibrillation in relation to multimorbidity status changes over time and the impact of ABC pathway compliance: a nationwide cohort study.

Patients with atrial fibrillation (AF) commonly have associated comorbidities. The primary aim was to determine the effect of increasing numbers of comorbidity on clinical outcomes. The secondary aims were (1) the association of comorbidities with oral anticoagulants (OAC) discontinuation, and quality control, (2) the impact of holistic care based on the ABC pathway on clinical outcomes. The primary outcome was the composite of all-cause death, ischemic stroke/systemic embolism, major bleeding, and heart failure. A total of 3405 patients were enrolled; mean age 67.8 ± 11.3 years, 41.8% female. Compared to low comorbidity group [n = 897 (26.3%)], hazard ratios (HR) and 95% confidence intervals (CI) for the composite outcome in the high [n = 929 (27.3%)] and moderate comorbidity [n = 1579 (46.4%)] groups were 5.40 (4.20-6.94) and 2.54 (1.97-3.27), respectively. ABC pathway adherence was associated with reduction of the composite outcome overall (HR 0.63; 0.54-0.74). High comorbidity adversely impacted on OAC use, OAC discontinuation, and quality of warfarin control. If quality of anticoagulation control was included as part of the ABC pathway adherence, the reduction in composite outcome risk was greater (HR 0.46; 0.36-0.58). During 3-year follow-up, 33.9% changed from low- to the moderate-high comorbidity groups and 22.3% changed from moderate- to the high comorbidity group. In conclusion, comorbidity burden in AF patients is an important determinant of clinical outcomes, and changed over time. OAC use, OAC discontinuation, and quality of OAC control were impacted by comorbidity burden. ABC pathway adherence was associated with a reduced risk of adverse clinical outcomes.

Diagnostic Yield and Outcomes of Small Bowel Capsule Endoscopy in Patients with Small Bowel Bleeding Receiving Antithrombotics.

We aimed to determine the diagnostic yield and outcome of patients receiving antithrombotic drug therapy subjected to small bowel capsule endoscopy (SBCE) for the investigation of small bowel bleeding (SBB). A multicenter retrospective analysis of collected data from all patients undergoing SBCE for the investigation of SBB from March 2003 to June 2023 was performed. The diagnostic yield of SBCE was defined as the detection of positive findings that could explain the cause of the patient's bleeding. Rebleeding was defined as evidence of bleeding within 1 year after the index episode. During the study period, 8401 patients underwent SBCE for SBB investigation. Bleeding lesions were detected in 1103/2535 (43.5%) antithrombotic users, compared to 1113/5866 (18.9%) in nonusers (p < 0.00001). Following capsule endoscopy, a therapeutic intervention was possible in 390/2216 (17.5%) patients with a bleeding lesion. Rebleeding occurred in 927 (36.5%) of antithrombotic users (36.5%), compared to 795 (13.5%) of nonusers (13.5%, p < 0.00001). Both the diagnostic yield of SBCE and the rebleeding rates were higher in patients with SBB receiving antithrombotics. Therapeutic intervention was possible in a real-world setting only for a minority of patients with positive findings.

Clinical Implications and Management of Spontaneous Portosystemic Shunts in Liver Cirrhosis.

Portal hypertension from chronic liver disease leads to the formation of collateral blood vessels called spontaneous portosystemic shunts (SPSS). These shunts may form from existing vessels or through neo-angiogenesis. Their location affects clinical outcomes due to varying risks and complications. This review summarizes current knowledge on SPSS, covering their clinical impact and management strategies. Recent data suggest that SPSS increases the risk of variceal bleeding, regardless of shunt size. The size of the shunt is crucial in the rising incidence of hepatic encephalopathy (HE) linked to SPSS. It also increases the risk of portopulmonary hypertension and portal vein thrombosis. Detecting and assessing SPSS rely on computed tomography (CT) and magnetic resonance imaging. CT enables precise measurements and the prediction of cirrhosis progression. Management focuses on liver disease progression and SPSS-related complications, like HE, variceal bleeding, and portopulmonary hypertension. Interventional radiology techniques such as balloon-occluded, plug-assisted, and coil-assisted retrograde transvenous obliteration play a pivotal role. Surgical options are rare but are considered when other methods fail. Liver transplantation (LT) often resolves SPSS. Intraoperative SPSS ligation is still recommended in patients at high risk for developing HE or graft hypoperfusion.

Clinical implementation of partial splenic artery embolization for the prevention of recurrent bleeding from esophageal varices in portal hypertension.

OBJECTIVE: Aim: To evaluate the effectiveness of PSAE for secondary prevention of VB episodes in patients with chronic liver disease (CLD) and CSPH. PATIENTS AND METHODS: Materials and Methods: One hundred twenty patients (from 2008 to 2020) were submitted of PSAE as secondary prevention treatment. The results of the treatment of 27 patients between 2008 and 2012 (first period) were compared with those of 93 patients treated with PSAE since 2013 (second period), as procedure and management protocol were modificated. VB recurrence rate and mortality (related and non-related to bleeding episodes) were defined as study end-points in both groups at 12-months follow-up. RESULTS: Results: At 12-months follow-up, 11 (40,7 %) and 54 (58,1 %) patients in groups 1 and 2, respectively, were free from VBs (p=0,129). Overall mortality rate was significantly higher in group 1, as compared to group 2: 10 (37,0 %) versus 6 (6,4 %) patients, respectively (p<0,001), - due to higher frequency of fatal VB events (7 (26,0 %) vs. 3 (3,2 %) patients, respectively; p=0,001). CONCLUSION: Conclusions: PSAE is an effective treatment for secondary prevention of VB in patients with CLD and CSPS. The management protocol modification resulted in the decrease in overall mortality rate and mortality related to recurrent VB episodes.

Platelet inhibitor withdrawal and outcomes after coronary artery surgery: an individual patient data meta-analysis.

OBJECTIVES: To evaluate the association between guideline-conforming as compared to shorter than recommended withdrawal period of P2Y12 receptor inhibitors prior to isolated on-pump coronary artery bypass grafting (CABG) and the incidence of severe bleeding and ischaemic events. Randomized controlled trials are lacking in this field. METHODS: We searched PUBMED, Embase and other suitable databases for studies including patients on P2Y12 receptor inhibitors undergoing isolated CABG and reporting bleeding and postoperative ischaemic events from 2013 to March 2024. The primary outcome was incidence of Bleeding Academic Research Consortium type 4 (BARC-4) bleeding defined as any of the following: perioperative intracranial bleeding, reoperation for bleeding, transfusion of ≥5 units of red blood cells, chest tube output of ≥2 l. The secondary outcome was postoperative ischaemic events according to the Academic Research Consortium 2 Consensus Document. Patient-level data provided by each observational trial were synthesized into a single dataset and analysed using a 2-stage IPD-MA. RESULTS: Individual data of 4837 patients from 7 observational studies were synthesized. BARC-4 bleeding, 30-day mortality and postoperative ischaemic events occurred in 20%, 2.6% and 5.2% of patients. After adjusting for EuroSCORE II and cardiopulmonary bypass time, guideline-conforming withdrawal was associated with decreased BARC-4 bleeding risk in patients on clopidogrel [adjusted odds ratio (OR) 0.48; 95% confidence intervals (CI) 0.28-0.81; P = 0.006] and a trend towards decreased risk in patients on ticagrelor (adjusted OR 0.48; 95% CI 0.22-1.05; P = 0.067). Guideline-conforming withdrawal was not significantly associated with 30-day mortality risk (clopidogrel: adjusted OR 0.70; 95% CI 0.30-1.61; ticagrelor: adjusted OR 0.89; 95% CI 0.37-2.18) but with decreased risk of postoperative ischaemic events in patients on clopidogrel (clopidogrel: adjusted OR 0.50; 95% CI 0.30-0.82; ticagrelor: adjusted OR 0.78; 95% CI 0.45-1.37). BARC-4 bleeding was associated with 30-day mortality risk (adjusted OR 4.76; 95% CI 2.67-8.47; P < 0.001). CONCLUSIONS: Guideline-conforming preoperative withdrawal of ticagrelor and clopidogrel was associated with a 50% reduced BARC-4 bleeding risk when corrected for EuroSCORE II and cardiopulmonary bypass time but was not associated with increased risk of 30-day mortality or postoperative ischaemic events.

Abdominal Drains After Laparoscopic Sleeve Gastrectomy: Should They Be Used?

Purpose: Laparoscopic sleeve gastrectomy (LSG) is one of the most common surgical procedures worldwide for the treatment of morbid obesity. Blake-type drains are widely used in this procedure despite the lack of clear evidence regarding their benefits in the diagnosis and treatment of common postoperative complications such as gastric suture line leak (GSLL) and postoperative bleeding (PB). Materials and Methods: A retrospective descriptive study with prospective case registry was conducted, analyzing all patients who underwent LSG between January 2012 and December 2022 at a high-volume center. Our primary outcome was to evaluate the role of drains for diagnosis and treatment of GSLL and PB in LSG. Our secondary outcome was to determine drain related surgical site infection (DRSSI) rate. Results: A total of 335 LSG were performed in the studied period. In all patients one abdominal drain was placed during surgery. Six GSLL (1.79%) and 5 PB (1.49%) were recorded. Drain placement did not prove to ensure early diagnosis or conservative management of GSLL or PB after LSG. Furthermore, an incidence of DRSSI of 4.1% (14 patients) was found. Conclusion: In our study, no clear diagnostic or therapeutic benefits of the systematic use of drains for GSLL or PB in LSG was found; but drain use did show a considerable rate of DRSSI, which must be taken into consideration prior to considering drain systematic use. While no randomized prospective trials have been performed, the retrospective data does not support drain systematic use.

Etiologies of Splenic Venous Hypertension: A Review.

Splenic venous hypertension or left-sided portal hypertension is a rare condition caused by an obstruction of the splenic vein. Usually, it presents with upper gastrointestinal bleeding in the absence of liver disease. Etiologies can be classified based on the mechanism of development of splenic vein hypertension: compression, stenosis, inflammation, thrombosis, and surgically decreased splenic venous flow. Diagnosis is established by various imaging modalities and should be suspected in patients with gastric varices in the absence of esophageal varices, splenomegaly, or cirrhosis. The management and prognosis vary depending on the underlying etiology but generally involve reducing splenic venous pressure. The aim of this review was to summarize the etiologies of splenic venous hypertension according to the mechanism of development.

Color-coded parametric imaging support display of vessel hemorrhage-an in vitro experiment and clinical validation study.

Background: Digital Subtraction Angiography (DSA) is currently the most effective diagnostic method for vascular diseases, but it is still subject to various factors, resulting in uncertain diagnosis. Therefore, a new technology is needed to help clinical doctors improve diagnostic accuracy and efficiency. Purpose: The objective of the study was to investigate the effect of utilizing color-coded parametric imaging techniques on the accuracy of identifying active bleeding through DSA, the widely accepted standard for diagnosing vascular disorders. Methods: Several variables can delay the diagnosis and treatment of active bleeding with DSA. To resolve this, we carried out an in vitro simulation experiment to simulate vascular hemorrhage and utilized five color-coded parameters (area under curve, time to peak, time-of-arrival, transit time, and flow rate of contrast agent) to determine the optimal color coding parameters. We then verified it in a clinical study. Results: Five different color-coded parametric imaging methods were compared and the time-of-arrival color coding was the most efficient technique for diagnosing active hemorrhage, with a statistically significant advantage (P < 0.001). In clinical study, 135 patients (101 with confirmed bleeding and 34 with confirmed no bleeding) were collected. For patients whose bleeding could not be determined using DSA alone (55/101) and whose no bleeding could not be diagnosed by DSA alone (35/55), the combination of time-of-arrival color parametric imaging was helpful for diagnosis, with a statistically significant difference (P < 0.01 and P = 0.01). Conclusions: The time-of-arrival color coding imaging method is a valuable tool for detecting active bleeding. When combined with DSA, it improves the visual representation of active hemorrhage and improves the efficiency of diagnosis.

Polypoid Large Intestinal Involvement of Metastatic Castrate-Resistant Prostate Cancer: A Case Report.

Introduction: Prostate cancer most commonly metastasizes to the bone and lymph nodes. Gastrointestinal metastasis has been noted in the literature but appears to be an exceedingly uncommon phenomenon. Large intestinal involvement in particular has been reported on only a few occasions, and never concomitantly with small intestinal metastatic involvement. Case Report: We report the case of a 69-year-old gentleman with metastatic castrate-resistant prostate cancer with development of gastrointestinal symptomatology with extensive investigation eventually revealing small and large intestinal polyps subsequently confirmed to be representative of metastatic prostate cancer. Conclusion: This case demonstrates the importance of maintaining a wide differential diagnosis in the context of gastrointestinal symptomatology in malignancy. Thorough endoscopic evaluation may be necessary in such cases in order to identify potential metastatic malignancy in otherwise relatively unremarkable appearing polyps.

Rare Colonic Dieulafoy Lesions: A Case Series.

Dieulafoy lesions (DLs) are infrequent causes of gastrointestinal bleeding (GIB) but can cause hemorrhage with a high risk of re-bleeds. They are most noted in the stomach, but this case series of three colonic DLs highlights even more rare causes of lower GIB. Three patients presented with blood loss and were found to have colonic DLs. All of them had esophagogastroduodenoscopies (EGDs) that were unremarkable, and they subsequently underwent a colonoscopy, which then showed oozing DLs. First, a 63-year-old woman had a week of maroon-colored stools but no use of blood thinners, prior GIB, or peptic ulcers. Next, an 81-year-old man presented with dyspnea and had a two-week history of melena. Three years later, he presented with two oozing lesions on a colonoscopy, which likely indicated a repeat DL. This was followed by multiple admissions for GIB. The lesions in these two cases were treated with epinephrine and hemostatic clips. Lastly, a 49-year-old man presented with hematochezia leading to shock, requiring transfusions, vasopressors, and ICU care. Computed tomography angiography (CTA) showed intraluminal contrast extraversion in the ascending colon, leading to interventional radiology (IR)-guided coil for suspected DL. Diagnosis can be hard, but early identification through endoscopy can help decrease mortality rates. Therefore, it is crucial to keep this on the list of differential diagnoses in cases with no other identifiable sources to allow for timely management.

Characterization of recombinant Factor IX fusion proteins enabling subcutaneous administration.

BACKGROUND: The X-linked bleeding disorder Hemophilia B, caused by mutation(s) in the coagulation factor IX (FIX) gene, leads to partial or total loss of its function requiring lifelong FIX replacement therapy. Although new recombinant FIX (rIX) therapeutics like albumin-fusion proteins (rIX-FP) enable longer plasma half-life and thus less frequent administration, the complexity of intravenous (IV) injection remains. OBJECTIVES: The study aims to characterize rIX-FP variants with anticipated enhanced specific activity, which would leverage rIX-FP's superior pharmacokinetic (PK) profile with beneficial characteristics for subcutaneous (SC) administration. METHODS: Two rIX-FP variants, R338L ("Padua-variant") and R338L/E410K, were characterized in vitro. PK profiles of FIX antigen and activity levels were evaluated in FIX-deficient mice after IV and SC administration of these variants (dosing based on antigen levels). The efficacy of the most promising variant was tested after IV and SC administration (dosing based on activity) in a tail-clip bleeding model. A marketed wildtype (WT) rIX-FP product served as the comparator. RESULTS: Both rIX-FP variants showed a 4- to 5-fold increase in specific activity in vitro compared to rIX(WT)-FP, whilst FXIa-mediated activation was the fastest for rIX(WT)-FP and rIX(R338L)-FP. Compared to rIX(WT)-FP and rIX(R338L/E410K)-FP, rIX(R338L)-FP exhibited higher FIX activity exposure after IV and SC administration, and demonstrated comparable efficacy towards rIX(WT)-FP in reducing bleeding time and blood loss in FIX-deficient mice requiring ∼4 times lower protein amount. CONCLUSIONS: rIX(R338L)-FP was shown to be a promising candidate for SC administration, exhibiting increased specific activity combined with higher activity-based exposure, and indicating efficacy at lower protein dose.