Initial Hemorrhage Control Procedure for Splenic Injuries May Affect Risk of Venous Thromboembolism.

INTRODUCTION: Venous thromboembolism (VTE) continues to be a major cause of morbidity in trauma. It is unclear whether the type of hemorrhage control procedure (i.e., splenectomy versus angioembolization) is associated with an increased risk of VTE. We hypothesize that hemodynamically stable patients undergoing angioembolization for blunt high-grade splenic injuries have lower rates of VTE compared to those undergoing splenectomy. METHODS: The American College of Surgeons Trauma Quality Program dataset from 2017 to 2019 was queried to identify all patients with American Association for the Surgery of Trauma grade 3-5 blunt splenic injuries. Outcomes including VTE rates were compared between those who were managed with splenectomy versus angioembolization. Propensity score matching (1:1) was performed adjusting for age, sex, initial vital signs, Injury Severity Score, and splenic injury grade. RESULTS: The analysis included 4698 matched patients (splenectomy [n = 2349] and angioembolization [n = 2349]). The median (interquartile range) age was 41 (27-58) years and 69% were male. Patients were well matched between groups. Angioembolization was associated with significantly lower VTE than splenectomy (2.2% versus 3.4%, P = 0.010) despite less use of VTE chemoprophylaxis (70% versus 80%, P < 0.001), as well as a relative delay in initiation of chemoprophylaxis (44 h versus 33 h, P < 0.001). Hospital and intensive care unit length of stay and mortality were also significantly lower in the angioembolization group. CONCLUSIONS: Angioembolization is associated with a significantly lower incidence of VTE than splenectomy. Thus, angioembolization should be considered for initial management of hemodynamically stable patients with high-grade blunt splenic injuries in whom laparotomy is not otherwise indicated.

Clinical Outcomes of Splenic Artery Embolization Versus Splenectomy in the Management of Hemodynamically Stable High-Grade Blunt Splenic Injuries: A National Analysis.

INTRODUCTION: This study aims to compare the outcomes of splenic artery embolization (SAE) versus splenectomy in adult trauma patients with high-grade blunt splenic injuries. METHODS: This retrospective analysis of the American College of Surgeons Trauma Quality Improvement Program database (2017-2021) compared SAE versus splenectomy in adults with blunt high-grade splenic injuries (grade ≥ IV). Patients were stratified first by hemodynamic status then splenic injury grade. Outcomes included in-hospital mortality, intensive care unit length of stay (ICU-LOS), and transfusion requirements at four and 24 h from arrival. RESULTS: Three thousand one hundred nine hemodynamically stable patients were analyzed, with 2975 (95.7%) undergoing splenectomy and 134 (4.3%) with SAE. One thousand eight hundred sixty five patients had grade IV splenic injuries, and 1244 had grade V. Patients managed with SAE had 72% lower odds of in-hospital mortality (odds ratio [OR] 0.28; P = 0.002), significantly shorter ICU-LOS (7 versus 9 d, 95%, P = 0.028), and received a mean of 1606 mL less packed red blood cells at four h compared to those undergoing splenectomy. Patients with grade IV or V injuries both had significantly lower odds of mortality (IV: OR 0.153, P < 0.001; V: OR 0.365, P = 0.041) and were given less packed red blood cells within four h when treated with SAE (2056 mL versus 405 mL, P < 0.001). CONCLUSIONS: SAE may be a safer and more effective management approach for hemodynamically stable adult trauma patients with high-grade blunt splenic injuries, as demonstrated by its association with significantly lower rates of in-hospital mortality, shorter ICU-LOS, and lower transfusion requirements compared to splenectomy.

Real time organ hypoperfusion detection using Indocyanine Green in a piglet model.

BACKGROUND: Preserving sufficient oxygen supply to the tissue is fundamental for maintaining organ function. However, our ability to identify those at risk and promptly recognize tissue hypoperfusion during abdominal surgery is limited. To address this problem, we aimed to develop a new method of perfusion monitoring that can be used during surgical procedures and aid surgeons' decision-making. METHODS: In this experimental porcine study, thirteen subjects were randomly assigned one organ of interest [stomach (n = 3), ascending colon (n = 3), rectum (n = 3), and spleen (n = 3)]. After baseline perfusion recordings, using high-frequency, low-dose bolus injections with weight-adjusted (0.008 mg/kg) ICG, organ-supplying arteries were manually and completely occluded leading to hypoperfusion of the target organ. Continuous organ perfusion monitoring was performed throughout the experimental conditions. RESULTS: After manual occlusion of pre-selected organ-supplying arteries, occlusion of the peripheral arterial supply translated in an immediate decrease in oscillation signal in most organs (3/3 ventricle, 3/3 ascending colon, 3/3 rectum, 2/3 spleen). Occlusion of the central arterial supply resulted in a further decrease or complete disappearance of the oscillation curves in the ventricle (3/3), ascending colon (3/3), rectum (3/3), and spleen (1/3). CONCLUSION: Continuous organ-perfusion monitoring using a high-frequency, low-dose ICG bolus regimen can detect organ hypoperfusion in real-time.

Long-Term Effects of Proximal Splenic Artery Embolization on Splenic Volume and Platelet Count.

BACKGROUND: The spleen is the most commonly injured visceral organ in blunt abdominal trauma. Post-splenectomy infection risk has led to the shift toward spleen preserving procedures and splenic artery embolization (SAE) is now the treatment of choice for hemodynamically stable patients with splenic injury. This study aims to assess the long-term effect of SAE on splenic volume and platelet count. MATERIALS AND METHODS: Using CPT codes, 66 patients who underwent SAE were identified, and 14 of those who had the necessary imaging and laboratory follow-up were included in the study. Indications for SAE were portal hypertension in 8 patients, bleeding in 4 patients, and thrombocytopenia in 1, and one patient had a separate indication. Splenic volume was calculated by automated volumetric software (Aquarius, TeraRecon, Inc.). Paired t-tests were performed to compare splenic volume and platelets before and after SAE. RESULTS: Fourteen patients (7 males, 7 females) with a mean age of 51 ± 11.95 years underwent SAE and were followed by a repeat computed tomography scan at an average of 733.57 days. Nine SAEs were performed using vascular plugs, 3 using micro coils, and 2 out of that were with Gelfoam slurry, and 2 using coils only. All embolizations were technically successful with complete cessation of flow. Mean splenic volumes pre- and post-SAE were 903.5 ± 523.73 cm3 and 746.5 ± 511.95 cm3, respectively, representing a mean decrease of 8.31% compared to baseline [P = 0.346]. Minimum platelet counts (x103) pre-SAE (within 3 months) and post-SAE (2 weeks to 3 months after the procedure) were 55.79 ± 57.11 and 116 ± 145.40, respectively. The minimum platelet count showed a statistically significant mean increase of 134.92% (P = 0.033). CONCLUSIONS: The splenic volume is not altered significantly by SAE in the long term. Similarly, the platelet count is also not significantly altered at 3 months follow-up. This study, although small, suggests that SAE is a safe intervention that can preserve splenic volume and function in the long term.

Comparing the Warshaw technique with vessel-preservation in laparoscopic spleen preserving distal pancreatectomy: is there a better approach?

BACKGROUND: Laparoscopic spleen-preserving distal pancreatectomy (LSPDP) can be accomplished with either resection of the splenic vessels via the Warshaw Technique (WT) or via preservation of the splenic vessels (SVP). Our study aims to compare outcomes for the two methods of LSPDP. METHODS: We performed a retrospective chart review with intent-to-treat analysis of adults undergoing LSPDP at a single institution from 2009 to 2021. We compared demographic characteristics, operative parameters, oncologic pathology review, and postoperative outcomes. RESULTS: There were 102 consecutive cases of LSPDP (59 WT, 43 SVP) over 12 years. The rate of successful spleen preservation was not significantly different between the two groups (76.3%WT, 65.1%VSP,p = 0.27). Rates of conversion to laparotomy, postoperative complications including pancreatic fistulas and splenic infarcts and amount of intraoperative blood loss were similar between the groups. Median operative time was significantly shorter with the WT (141 vs. 177 min, p < 0.05). The median length of stay in hospital was not significantly different among the groups. CONCLUSION: Both techniques are safe and effective in preserving the spleen in laparoscopic distal pancreatectomy. Our experience suggests that the Warshaw Technique may be more efficient with respect to the use of limited operative resources.

Soluble thrombomodulin ameliorates aberrant hemostasis after rewarming in a rat accidental hypothermia model.

BACKGROUND: Accidental hypothermia (AH) sometimes leads to coagulation disorder, especially in severe AH. We previously demonstrated that intrasplenic platelet activation caused aberrant hemostasis and thrombus formation after rewarming in a murine AH model. However, no study has focused on the appropriate management of platelets causing coagulation activation after rewarming of AH. We investigated whether or not recombinant soluble thrombomodulin (rTM) can suppress thrombosis formation after rewarming using a rat AH model. METHODS: Wistar rats were exposed to an ambient temperature of -20 °C under general anesthesia until their rectal temperature decreased to 26 °C. The Hypo group rats (n = 5) were immediately euthanized, while the Hypo/Re group (n = 5) and rTM group rats (n = 5), which were administered rTM (1 mg/kg) via the tail vein, were rewarmed until the rectal temperature returned to 34 °C and then euthanized 6 h later. Tissue and blood samples were collected from all rats for histopathological and coagulation analyses at euthanasia. RESULTS: There was no significant change in the D-dimer level in the Hypo group rats, while the D-dimer level was significantly elevated at 6 h after rewarming in the Hypo/Re group rats (P = 0.015), and histopathology detected both fibrin and platelets in the renal glomerulus. However, the rTM group rats did not show any elevation of the D-dimer levels at 6 h after rewarming, and no fibrin was noted on histopathology. CONCLUSIONS: rTM may be useful as an appropriate anticoagulant in cases of aberrant hemostasis after rewarming of AH.

Immune Function After Splenic Artery Embolization for Blunt Trauma: Long-Term Assessment of CD27+ IgM B-Cell Levels.

Splenic artery embolization (SAE) plays a critical role in the treatment of high-grade splenic injury not requiring emergent laparotomy. SAE preserves splenic tissue, and growing evidence demonstrates preserved short-term splenic immune function after SAE. However, long-term function is less studied. Patients who underwent SAE for blunt abdominal trauma over a 10-year period were contacted for long-term follow-up. Sixteen participants (sex: women, 10, and men, 6; age: median, 34 years, and range, 18-67 years) were followed up at a median of 7.7 years (range, 4.7-12.8 years) after embolization. Splenic lacerations were of American Association for the Surgery of Trauma grades III to V, and 14 procedures involved proximal embolization. All individuals had measurable levels of IgM memory B cells (median, 14.30 as %B cells), splenic tissue present on ultrasound (median, 122 mL), and no history of severe infection since SAE. In conclusion, this study quantitatively demonstrated that long-term immune function remains after SAE for blunt abdominal trauma based on the IgM memory B cell levels.

American Society of Emergency Radiology Multicenter Blunt Splenic Trauma Study: CT and Clinical Findings.

Background Treatment of blunt splenic trauma (BST) continues to evolve with improved imaging for detection of splenic vascular injuries. Purpose To report on treatments for BST from 11 trauma centers, the frequency and clinical impact of splenic vascular injuries, and factors influencing treatment. Materials and Methods Patients were retrospectively identified as having BST between January 2011 and December 2018, and clinical, imaging, and outcome data were recorded. Patient data were summarized descriptively, both overall and stratified by initial treatment received (nonoperative management [NOM], angiography, or surgery). Regression analyses were used to examine the primary outcomes of interest, which were initial treatment received and length of stay (LOS). Results This study evaluated 1373 patients (mean age, 42 years ± 18; 845 men). Initial treatments included NOM in 849 patients, interventional radiology (IR) in 240 patients, and surgery in 284 patients. Rates from CT reporting were 22% (304 of 1373) for active splenic hemorrhage (ASH) and 20% (276 of 1373) for contained vascular injury (CVI). IR management of high-grade injuries increased 15.6%, from 28.6% (eight of 28) to 44.2% (57 of 129) (2011-2012 vs 2017-2018). Patients who were treated invasively had a higher injury severity score (odds ratio [OR], 1.04; 95% CI: 1.02, 1.05; P < .001), lower temperature (OR, 0.97; 95% CI: 0.97, 1.00; P = .03), and a lower hematocrit (OR, 0.96; 95% CI: 0.93, 0.99; P = .003) and were more likely to show ASH (OR, 8.05; 95% CI: 5.35, 12.26; P < .001) or CVI (OR, 2.70; 95% CI: 1.64, 4.44; P < .001) on CT images, have spleen-only injures (OR, 2.35; 95% CI: 1.45, 3.8; P < .001), and have been administered blood product for fewer than 24 hours (OR, 2.35; 95% CI: 1.58, 3.51; P < .001) compared with those chosen for NOM, after adjusting for key demographic and clinical variables. After adjustment, factors associated with a shorter LOS were female sex (OR, 0.84; 95% CI: 0.73, 0.96; P = .009), spleen-only injury (OR, 0.72; 95% CI: 0.6, 0.86; P < .001), higher admission hematocrit (OR, 0.98; 95% CI: 0.6, 0.86; P < .001), and presence of ASH at CT (OR, 0.74; 95% CI: 0.62, 0.88; P < .001). Conclusion Contained vascular injury and active splenic hemorrhage (ASH) were frequently reported, and rates of interventional radiologic management increased during the study period. ASH was associated with a shorter length of stay, and patients with ASH had eight times the odds of undergoing invasive treatment compared with undergoing nonoperative management. © RSNA, 2021 See also the editorial by Patlas in this issue.

Exploring human splenic red pulp vasculature in virtual reality: details of sheathed capillaries and the open capillary network.

We reconstructed serial sections of a representative adult human spleen to clarify the unknown arrangement of the splenic microvasculature, such as terminal arterioles, sheathed capillaries, the red pulp capillary network and venules. The resulting 3D model was evaluated in virtual reality (VR). Capillary sheaths often occurred after the second or third branching of a terminal arteriole and covered its capillary side or end branches. The sheaths started directly after the final smooth muscle cells of the arteriole and consisted of cuboidal CD271++ stromal sheath cells surrounded and infiltrated by B lymphocytes and macrophages. Some sheaths covered up to four sequential capillary bifurcations thus forming bizarre elongated structures. Each sheath had a unique form. Apart from symmetric dichotomous branchings inside the sheath, sheathed capillaries also gave off side branches, which crossed the sheath and freely ended at its surface. These side branches are likely to distribute materials from the incoming blood to sheath-associated B lymphocytes and macrophages and thus represent the first location for recognition of blood-borne antigens in the spleen. A few non-sheathed bypasses from terminal arterioles to the red pulp capillary network also exist. Red pulp venules are primarily supplied by sinuses, but they also exhibit a few connections to the capillary network. Thus, the human splenic red pulp harbors a primarily open microcirculation with a very minor closed part.

Peripheral blood mononuclear cell activation sustains seizure activity.

OBJECTIVE: The influx of immune cells and serum proteins from the periphery into the brain due to a dysfunctional blood-brain barrier (BBB) has been proposed to contribute to the pathogenesis of seizures in various forms of epilepsy and encephalitis. We evaluated the pathophysiological impact of activated peripheral blood mononuclear cells (PBMCs) and serum albumin on neuronal excitability in an in vitro brain preparation. METHODS: A condition of mild endothelial activation induced by arterial perfusion of lipopolysaccharide (LPS) was induced in the whole brain preparation of guinea pigs maintained in vitro by arterial perfusion. We analyzed the effects of co-perfusion of human recombinant serum albumin with human PBMCs activated with concanavalin A on neuronal excitability, BBB permeability (measured by FITC-albumin extravasation), and microglial activation. RESULTS: Bioplex analysis in supernatants of concanavalin A-stimulated PBMCs revealed increased levels of several inflammatory mediators, in particular interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, interferon (INF)-γ, IL-6, IL-10, IL-17A, and MIP3α. LPS and human albumin arterially co-perfused with either concanavalin A-activated PBMCs or the cytokine-enriched supernatant of activated PBMCs (1) modulated calcium-calmodulin-dependent protein kinase II at excitatory synapses, (2) enhanced BBB permeability, (3) induced microglial activation, and (4) promoted seizure-like events. Separate perfusions of either nonactivated PBMCs or concanavalin A-activated PBMCs without LPS/human albumin (hALB) failed to induce inflammatory and excitability changes. SIGNIFICANCE: Activated peripheral immune cells, such as PBMCs, and the extravasation of serum proteins in a condition of BBB impairment contribute to seizure generation.

Risk Factors for Failure of Splenic Angioembolization: A Multicenter Study of Level I Trauma Centers.

BACKGROUND: Angioembolization (AE) is an adjunct to nonoperative management (NOM) of splenic injuries. We hypothesize that failure of AE is associated with blood transfusion, grade of injury, and technique of AE. METHODS: We performed a retrospective (2010-2017) multicenter study (nine Level I trauma centers) of adult trauma patients with splenic injuries who underwent splenic AE. Variables included patient physiology, injury grade, transfusion requirement, and embolization technique. The primary outcome was NOM failure requiring splenectomy. Secondary outcomes were mortality, complications, and length of stay. RESULTS: A total of 409 patients met inclusion criteria; only 33 patients (8%) required delayed splenectomy. Patients who failed received more blood in the first 24 h (P = 0.009) and more often received massive transfusion (P = 0.01). There was no difference in failure rates for grade of injury, contrast blush on computed tomography, and branch embolized. After logistic regression, transfusion in the first 24 h was independently associated with failure of NOM (P = 0.02). Patients who failed NOM had more complications (P = 0.002) and spent more days in the intensive care unit (P < 0.0001), on the ventilator (P = 0.0001), and in the hospital (P < 0.0001). Patients who failed NOM had a higher mortality (15% versus 3%, P = 0.007), and delayed splenectomy was independently associated with mortality (odds ratio, 4.2; 95% confidence interval, 1.2-14.7; P = 0.03). CONCLUSIONS: AE for splenic injury leads to effective NOM in 92% of patients. Transfusion in the first 24 h is independently associated with failure of NOM. Patients who required a delayed splenectomy suffered more complications and had higher hospital length of stay. Failure of NOM is independently associated with a fourfold increase in mortality.

Splenic switch-off as a predictor for coronary adenosine response: validation against 13N-ammonia during co-injection myocardial perfusion imaging on a hybrid PET/CMR scanner.

BACKGROUND: Inadequate coronary adenosine response is a potential cause for false negative ischemia testing. Recently, the splenic switch-off (SSO) sign has been identified as a promising tool to ascertain the efficacy of adenosine during vasodilator stress cardiovascular magnetic resonance imaging (CMR). We assessed the value of SSO to predict adenosine response, defined as an increase in myocardial blood flow (MBF) during quantitative stress myocardial perfusion 13 N-ammonia positron emission tomography (PET). METHODS: We prospectively enrolled 64 patients who underwent simultaneous CMR and PET myocardial perfusion imaging on a hybrid PET/CMR scanner with co-injection of gadolinium based contrast agent (GBCA) and 13N-ammonia during rest and adenosine-induced stress. A myocardial flow reserve (MFR) of  > 1.5 or ischemia as assessed by PET were defined as markers for adequate coronary adenosine response. The presence or absence of SSO was visually assessed. The stress-to-rest intensity ratio (SIR) was calculated as the ratio of stress over rest peak signal intensity for splenic tissue. Additionally, the spleen-to-myocardium ratio, defined as the relative change of spleen to myocardial signal, was calculated for stress (SMRstress) and rest. RESULTS: Sixty-one (95%) patients were coronary adenosine responders, but SSO was absent in 18 (28%) patients. SIR and SMRstress were significantly lower in patients with SSO (SIR: 0.56 ± 0.13 vs. 0.93 ± 0.23; p < 0.001 and SMRstress: 1.09 ± 0.47 vs. 1.68 ± 0.62; p < 0.001). Mean hyperemic and rest MBF were 2.12 ± 0.68 ml/min/g and 0.78 ± 0.26 ml/min/g, respectively. MFR was significantly higher in patients with vs. patients without presence of SSO (3.07 ± 1.03 vs. 2.48 ± 0.96; p = 0.038), but there was only a weak inverse correlation between SMRstress and MFR (R = -0.378; p = 0.02) as well as between SIR and MFR (R = -0.356; p = 0.004). CONCLUSIONS: The presence of SSO implies adequate coronary adenosine-induced MBF response. Its absence, however, is not a reliable indicator for failed adenosine-induced coronary vasodilatation.

A perisinusoidal niche for extramedullary haematopoiesis in the spleen.

Haematopoietic stresses mobilize haematopoietic stem cells (HSCs) from the bone marrow to the spleen and induce extramedullary haematopoiesis (EMH). However, the cellular nature of the EMH niche is unknown. Here we assessed the sources of the key niche factors, SCF (also known as KITL) and CXCL12, in the mouse spleen after EMH induction by myeloablation, blood loss, or pregnancy. In each case, Scf was expressed by endothelial cells and Tcf21(+) stromal cells, primarily around sinusoids in the red pulp, while Cxcl12 was expressed by a subset of Tcf21(+) stromal cells. EMH induction markedly expanded the Scf-expressing endothelial cells and stromal cells by inducing proliferation. Most splenic HSCs were adjacent to Tcf21(+) stromal cells in red pulp. Conditional deletion of Scf from spleen endothelial cells, or of Scf or Cxcl12 from Tcf21+ stromal cells, severely reduced spleen EMH and reduced blood cell counts without affecting bone marrow haematopoiesis. Endothelial cells and Tcf21(+) stromal cells thus create a perisinusoidal EMH niche in the spleen, which is necessary for the physiological response to diverse haematopoietic stresses.

Splenic Artery Angioembolization is Associated with Increased Venous Thromboembolism.

BACKGROUND: Angioembolization has become an increasingly utilized adjunct for splenic preservation after trauma. Embolization of the splenic artery may produce a transient systemic hypercoagulable state. This study was designed to determine the risk of venous thromboembolism (VTE) in blunt trauma patients managed nonoperatively with splenic angioembolization, relative to those managed without. METHOD: Retrospective review of the American College of Surgeons Trauma Quality Improvement Performance (TQIP) Database from 2013 to 2016. Adult (>16 years) patients with isolated, severe (Grades III-V) blunt splenic injuries managed nonoperatively who received pharmacological VTE prophylaxis formed the study population. Outcomes included deep venous thrombosis (DVT), pulmonary embolism (PE), or any VTE. RESULTS: A total of 2643 patients met inclusion criteria (69.1% Grade III, 26.5% Grade IV, 4.5% Grade V). The incidence of DVT was 4.5% in patients who underwent angioembolization, compared to 1.4% in patients who did not (p<0.001). Multivariable analysis showed that angioembolization was an independent risk factor for both DVT (OR 2.65, p = 0.006) and any VTE (OR 2.04, p = 0.01). Analysis according to splenic injury Grades showed that angioembolization remained an independent risk factor for DVT (p = 0.004) in the Grade IV-V injury group, and for VTE (p<0.01) in the Grade III injury group. Initiation of pharmacological VTE prophylaxis 48 h after admission was associated with increased VTE rates in comparison to early initiation (OR 1.75, p = 0.02) CONCLUSIONS: Splenic artery angioembolization may be an independent risk factor for VTE events in isolated, severe blunt splenic trauma managed nonoperatively. Early prophylaxis with LMWH after intervention should be strongly considered.

Splenic artery loops: Potential splenic plexus stimulation sites for neuroimmunomodulatory-based anti-inflammatory therapy?

INTRODUCTION: The splenic plexus might represent a novel neuroimmunomodulatory therapeutic target as electrical stimulation of this tissue has been shown to have beneficial anti-inflammatory effects. Tortuous splenic artery segments (splenic artery loops), including their surrounding nerve plexus, have been evaluated as potential stimulation sites in humans. At present, however, our understanding of these loops and their surrounding nerve plexus is incomplete. This study aims to characterize the dimensions of these loops and their surrounding nerve tissue. MATERIALS AND METHODS: Six formaldehyde fixed human cadavers were dissected and qualitative and quantitative macro- and microscopic data on splenic artery loops and their surrounding nerve plexus were collected. RESULTS: One or multiple loops were observed in 83% of the studied specimens. These loops, including their surrounding nerve plexus could be easily dissected free circumferentially thereby providing sufficient space for further surgical intervention. The splenic plexus surrounding the loops contained a significant amount of nerves that contained predominantly sympathetic fibers. CONCLUSION: The results of this study support that splenic artery loops could represent suitable electrical splenic plexus stimulation sites in humans. Dimensions with respect to loop height and width, provide sufficient space for introduction of surgical instruments and electrode implantation, and, the dissected neurovascular bundles contain a substantial amount of sympathetic nerve tissue. This knowledge may contribute to further development of surgical techniques and neuroelectrode interface design.

Mutations in RPSA and NKX2-3 link development of the spleen and intestinal vasculature.

Idiopathic intestinal varicosis is a developmental disorder defined by dilated and convoluted submucosal veins in the colon or small bowel. A limited number of families with idiopathic intestinal varices has been reported, but the genetic cause has not yet been identified. We performed whole-exome and targeted Sanger sequencing of candidate genes in five intestinal varicosis families. In four families, mutations in the RPSA gene were found, a gene previously linked to congenital asplenia. Individuals in these pedigrees had intestinal varicose veins and angiodysplasia, often in combination with asplenia. In a further four-generation pedigree that only showed intestinal varicosities, the RPSA gene was normal. Instead, a nonsense mutation in the homeobox gene NKX2-3 was detected which cosegregated with the disease in this large family with a LOD (logarithm of the odds) score of 3.3. NKX2-3 is a component of a molecular pathway underlying spleen and gut vasculature development in mice. Our results provide a molecular basis for familial idiopathic intestinal varices. We provide evidence for a relationship between the molecular pathways underlying the development of the spleen and intestinal mucosal vasculature that is conserved between humans and mice. We propose that clinical management of intestinal varices, should include assessment of a functional spleen.

Modern management of splenomegaly in patients with myelofibrosis.

Myelofibrosis (MF) is a chronic myeloproliferative neoplasm which can lead to massive splenomegaly secondary to extramedullary hematopoiesis. Patients frequently exhibit debilitating symptoms including pain and early satiety, in addition to cellular sequestration causing severe cytopenias. JAK 1/2 inhibitors, such as ruxolitinib and fedratinib, are the mainstay of therapy and produce significant and durable reductions in spleen volume. However, many patients are not eligible for JAK 2 inhibitor therapy or become refractory to treatment over time. Novel therapies are in development that can reduce the degree of splenomegaly for some of these patients. However, splenectomy, splenic irradiation, and partial splenic artery embolization remain valuable therapeutic options in select patients. In this review, we will discuss currently available pharmacologic therapies and describe promising drugs currently in development. We will also delve into the efficacy and safety concerns of splenectomy, splenic irradiation, and partial splenic artery embolization. Finally, we will propose a treatment algorithm to help guide clinicians in the management of symptomatic splenomegaly in patients with MF.

Stimulation of the hepatic arterial buffer response using exogenous adenosine: hepatic rest/stress perfusion imaging.

OBJECTIVES: The hepatic arterial buffer response is a mechanism mediated by adenosine whereby hepatic arterial perfusion (HAP) increases when portal flow decreases, and is implicated in liver disease. The first study aim was to measure HAP in patients undergoing myocardial perfusion imaging (MPI), thus developing hepatic arterial rest/stress perfusion imaging (HAPI). The second aim was to compare adenosine-induced changes in splenic perfusion (SP) and HAP with corresponding changes in myocardial blood flow (MBF). METHODS: Patients had MPI with 82Rb PET/CT using adenosine (n = 45) or regadenoson (n = 33) for stressing. SP and HAP were measured using a first-pass technique that gives HAP rather than total hepatic perfusion. Renal perfusion (RP) was also measured. RESULTS: Mean MBF and HAP increased after both adenosine ([stress-rest]/rest 1.1 and 0.8) and regadenoson (1.4 and 0.6), but the respective changes did not correlate. After adenosine, SP (- 0.48) and RP (- 0.26) both decreased. The change in SP correlated positively with the change in MBF (r = 0.36; p = 0.015) but did not correlate with change in HAP. After regadenoson, SP (0.2) and RP (0.2) both increased. The changes in SP correlated with the changes in MBF (r = 0.39; p = 0.025) and HAP (r = 0.39; p = 0.02). Changes in RP correlated with changes in HAP (r = 0.51; p = 0.0008) but not MBF. Resting SP (r = 0.32; p = 0.004), but not resting HAP, correlated with hepatic fat burden. Adenosine-induced change in HAP also correlated with hepatic fat (r = 0.29; p = 0.05). CONCLUSION: HAPI could be a useful new hepatic function test. Neither splenic 'switch-off' nor hepatic arterial 'switch-on' identifies adequacy of stress in MPI. KEY POINTS: • This article describes a new method for assessing arterial perfusion of the liver and its capacity to respond to an infusion of adenosine, a substance that normally 'drives' hepatic arterial flow. • Hepatic arterial flow increased in response to adenosine, sometimes dramatically. Adenosine is already used clinically to stimulate myocardial blood flow in patients with suspected coronary disease, but the increase in flow did not correlate with the corresponding increase in hepatic arterial flow. • Analogous to the use of adenosine in the myocardium, the increase in hepatic arterial flow in response to adenosine has the potential to be a new clinically useful method for the evaluation of hepatic arterial haemodynamics in liver disease.

Clinical Results of Distal Embolization in Grade V Splenic Injury: Four-Year Experience from a Single Regional Trauma Center.

PURPOSE: To evaluate the benefits and risks of splenic artery embolization (SAE) in patients with American Association for the Surgery of Trauma (AAST) grade V blunt spleen injury (BSI) MATERIALS AND METHODS: Medical records of 88 patients treated with SAE between April 2013 and May 2017 at a regional trauma care center were reviewed retrospectively. The BSI grade according to the AAST spleen injury scale (revised version 2018) was determined by using computed tomography (CT) images. A total of 42 patients (46.6%) had AAST grade V injury and were included in the analysis. Patient demographics, angiographic findings, embolization techniques, and technical and clinical outcomes, including splenic salvage rate and procedure-related complications, were examined. RESULTS: SAE was performed within 2 hours after admission for 78.5% of the patients. All patients underwent selective distal embolization (n = 42). Primary clinical success rate was 80.9% (n = 34), and secondary clinical success rate was 88.1% (n = 37). The clinical failure group consisted of 5 patients. Four patients underwent splenectomy, and 1 patient died due to acute respiratory distress syndrome after embolization. The splenic salvage rate was 85.7% (n = 36). No patient had sepsis at follow-up (median, 247.0 days; interquartile range, 92.0-688.0). Clinical success rates (P = .356) and spleen salvage rates (P = .197) of patients who were hemodynamically stable (n = 19) showed no significant differences from those who were unstable (n = 23). CONCLUSIONS: Distal embolization of grade V BSI is a safe and feasible procedure which is effective for successful spleen salvage.

Contemporary endovascular management of splenic vascular pathologies.

The spleen is a commonly injured organ and the splenic vasculature is also susceptible to inflammation and trauma, often resulting in aneurysm formation. Splenic artery aneurysms carry a high risk of rupture and are associated with high mortality and morbidity. Due to the advances in endovascular techniques and devices, endovascular management of splenic vascular pathologies is now considered a first-line strategy. Endovascular embolisation and advance techniques including balloon- or stent-assisted coil embolisation enables minimally invasive management option while preserving splenic function.