Severe small intestinal bacterial overgrowth syndrome after jejunal feeding requiring surgical intervention: a case report and review of the literature.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is a condition of unknown prevalence characterized by an excessive amount of bacteria in the small bowel, typically resulting in vague gastrointestinal symptoms with bloating being most commonly reported. Here we describe a severe case of SIBO leading to small bowel necrosis requiring surgical intervention. CASE PRESENTATION: A 55-year-old Hispanic female with gastric outlet obstruction secondary to a newly diagnosed gastric adenocarcinoma, receiving neoadjuvant chemotherapy, developed bloody gastrostomy output and rapidly progressing nausea and abdominal distention 3 days after jejunostomy tube placement and initiation of jejunal enteral nutrition. Imaging revealed diffuse pneumatosis and portal venous gas. Surgical exploration confirmed segmental bowel necrosis requiring resection. Histologic findings were consistent with SIBO. CONCLUSIONS: Presentation of severe SIBO in the setting of intestinal stasis secondary to gastric outlet after initiation of enteral feeds is a rare phenomenon. Early recognition and diagnosis of SIBO is critical in minimizing patient morbidity and mortality.

Improved retransplant outcomes: early evidence of the share35 impact.

BACKGROUND: Share 35 prioritizes offers of deceased donor livers to regional candidates with Model for End-Stage Liver Disease (MELD) ≥35 over local candidates with lower MELD scores. Analysis of Share35 has shown that overall 1- or 2-year post-transplant (LTx) outcomes have been unchanged while waitlist mortality has been reduced. However, these studies exclude retransplant (reLTx) recipients. This study aims to investigate the outcomes of liver retransplants in evaluating the impact of the Share35 policy. METHODS: A retrospective analysis of data from the United Network for Organ Sharing database over the period June 2011-June 2015 was performed. RESULTS: A total of 19,748 LTx and 312 reLTx recipients were identified. Of the LTx recipients, 9626 (48.7%) underwent transplant pre-Share 35 and 10,122 (51.3%) post-Share 35. 123 (39.4%) reLTx recipients underwent retransplantation pre-Share 35 and 189 (60.6%) post-Share 35. ReLTx recipients experienced improved 2-year graft survival post-Share 35 compared to pre-Share 35 (67% vs. 21.1%). Patient survival also improved at 2-years for reLTx recipients post-Share 35 compared to pre-Share 35 (69.2% vs. 33.1%). Transplant post-Share 35 was protective for both 2-year graft (HR = 0.669, CI = 0.454-0.985, p = 0.04) and patient (HR = 0.659, CI = 0.44-0.987, p = 0.003) survival. CONCLUSION: Share35 is associated with improved outcomes after retransplantation.

Eosinophils regulate peripheral B cell numbers in both mice and humans.

The view of eosinophils (Eos) as solely effector cells involved in host parasite defense and in the pathophysiology of allergic diseases has been challenged in recent years. In fact, there is a growing realization that these cells interact with other components of innate and adaptive immunity. For example, mouse Eos were recently demonstrated to promote plasma cell retention in the bone marrow. However, it remains unknown whether Eos influence the biology of normal B lymphocytes. In this study, we specifically assessed the effect of Eos on B cell survival, proliferation, and Ig secretion. Our data first revealed that the genetic deletion of Eos from NJ1638 IL-5 transgenic hypereosinophilic mice (previously shown to display profound B cell expansion) resulted in the near abolishment of the B cell lymphocytosis. In vitro studies using human tissues demonstrated Eos' proximity to B cell follicles and their ability to promote B cell survival, proliferation, and Ig secretion via a contact-independent mechanism. Additionally, this ability of Eos to enhance B cell responsiveness was observed in both T-independent and T-dependent B cell activation and appears to be independent of the activation state of Eos. Finally, a retrospective clinical study of hypereosinophilic patients revealed a direct correlation between peripheral blood eosinophil levels and B cell numbers. Taken together, our study identifies a novel role for Eos in the regulation of humoral immunity via their impact on B cell homeostasis and proliferation upon activation.

Location of Traumatic Cranial Epidural Hematoma Correlates with the Source of Hemorrhage: A 12-Year Surgical Review.

BACKGROUND: Epidural hematoma (EDH) can result in a catastrophic outcome of traumatic brain injury. Current management guidelines do not consider the source of hemorrhage in decision making. The purpose of this study was to examine the relationship between EDH location and the source of hemorrhage. METHODS: We report retrospectively reviewed, prospectively obtained surgical data of patients with acute traumatic cranial EDH treated between 2007 and 2018. Computed tomography (CT) scans were used to categorize EDH location as lateral or medial. The source of hemorrhage was identified intraoperatively by a single surgeon. RESULTS: Overall, of 92 evacuated EDHs (in 87 patients), 71 (77.2%) were in the lateral location. Arterial bleeding was the cause of EDH in 63.4% of the lateral EDHs and 9.2% of the medial EDHs (P < 0.0001). In the cases where surgery was done primarily to treat EDH, 65.3% had an arterial bleed source (P < 0.0001). In those treated for primary reasons other than EDH evacuation, 75% had a venous bleed source (P = 0.002). CONCLUSIONS: The location of EDH correlates with the source of hemorrhage. The decision to operate on EDH may be influenced by this factor.

Invasion of microglia/macrophages and granulocytes into the Mauthner axon myelin sheath following spinal cord injury of the adult goldfish, Carassius auratus.

Rapid activation of resident glia occurs after spinal cord injury. Somewhat later, innate and adaptive immune responses occur with the invasion of peripheral immune cells into the wound site. The activation of resident and peripheral immune cells has been postulated to play harmful as well as beneficial roles in the regenerative process. Mauthner cells, large identifiable neurons located in the hindbrain of most fish and amphibians, provided the opportunity to study the morphological relationship between reactive cells and Mauthner axons (M-axons) severed by spinal cord crush or by selective axotomy. After crossing in the hindbrain, the M-axons of adult goldfish, Carassius auratus, extend the length of the spinal cord. Following injury, the M-axon undergoes retrograde degeneration within its myelin sheath creating an axon-free zone (proximal dieback zone). Reactive cells invade the wound site, enter the axon-free dieback zone and are observed in the vicinity of the retracted M-axon tip as early as 3 hr postinjury. Transmission electron microscopy allowed the detection of microglia/macrophages and granulocytes, some of which appear to be neutrophil-like, at each of these locations. We believe that this is the first report of the invasion of such cells within the myelin sheath of an identifiable axon in the vertebrate central nervous system (CNS). We speculate that microglia/macrophages and granulocytes that are attracted within a few hours to the damaged M-axon are part of an inflammatory response that allows phagocytosis of debris and plays a role in the regenerative process. Our results provide the baseline from which to utilize immunohistochemical and genetic approaches to elucidate the role of non-neuronal cells in the regenerative process of a single axon in the vertebrate CNS.

Epidural venous plexus engorgement due to inferior vena cava thrombosis resulting in cauda equina syndrome: Case report and literature review.

BACKGROUND: Epidural venous plexus congestion at L5-S1 due to inferior vena cava (IVC) thrombosis led to an acute cauda equina syndrome (CES). Laminectomy to rule out an epidural abscess, allowing for resection of the dilated veins, led to immediate symptom resolution. CASE DESCRIPTION: A 47-year-old male presented with acute urinary retention and left greater than right lower extremity paresis of 2 weeks duration. Magnetic resonance imaging (MRI) revealed a contrast-enhancing space-occupying anterior epidural L5-S1 level lesion resulting in cauda equina compression. As the patient was septic, he underwent an emergency laminectomy for a presumed epidural abscess. Intraoperative findings, however, documented a markedly dilated epidural venous plexus secondary to a newly diagnosed IVC thrombus. One day postoperatively, the patient was symptom-free and neurologically intact. CONCLUSIONS: Here we report a patient who uniquely presented with a CES characterized by acute paraparesis. This was attributed to a massively engorged anterior lumbar epidural venous plexus attributed to newly diagnosed IVC thrombus.

Eosinophil purification from human bone marrow.

Eosinophils are innate immune cells that are best known for their involvement in host defense against parasitic infections and in asthma and allergic diseases. In vitro characterization of the function of human eosinophils has traditionally relied on the purification of these cells from the peripheral blood as reviewed in Chapter 2. Here, we describe a newly developed protocol for the purification of eosinophils from human bone marrow.

Purification of functional eosinophils from human bone marrow.

Eosinophils are granulocytic leukocytes that are best known for their involvement in host immune defense and pathologic states. More recently, they have also been shown to play a role in regulation of murine plasma cell homeostasis in the bone marrow, which prompted our investigation of human bone marrow eosinophils. However, effective methods to isolate eosinophils from human bone marrow thereby allowing comparisons with circulating eosinophils have not yet been described. Herein we describe the development of a novel, cost effective protocol for the purification of eosinophils from human bone marrow that allows us to obtain bone marrow eosinophils of near 100% purity after an 8-day culture system. Furthermore, we demonstrate that bone marrow eosinophils have characteristics similar to blood eosinophils, including the expression of IL-5Rα, the presence of eosinophil-specific granules, and similar activation kinetics upon phorbol myristate acetate and high-dose IL-5 stimulation. While migratory responses toward the chemokine CXCL12 differed between purified bone marrow and freshly isolated blood eosinophils, migratory responses were similar upon comparison of bone marrow eosinophils with blood eosinophils cultured ex vivo for 8 days prior to assay. Interestingly, a concurrent upregulation of CXCR4 expression was not observed in these cultured blood eosinophils. Taken together, we have overcome the existing challenges to the study of bone marrow eosinophils through our novel strategy for cell purification and have thus enabled future investigations of these cells and their role(s) in human health and disease.

Induction of malignant plasma cell proliferation by eosinophils.

The biology of the malignant plasma cells (PCs) in multiple myeloma (MM) is highly influenced by the bone marrow (BM) microenvironment in which they reside. More specifically, BM stromal cells (SCs) are known to interact with MM cells to promote MM cell survival and proliferation. By contrast, it is unclear if innate immune cells within this same space also actively participate in the pathology of MM. Our study shows for the first time that eosinophils (Eos) can contribute to the biology of MM by enhancing the proliferation of some malignant PCs. We first demonstrate that PCs and Eos can be found in close proximity in the BM. In culture, Eos were found to augment MM cell proliferation that is predominantly mediated through a soluble factor(s). Fractionation of cell-free supernatants and neutralization studies demonstrated that this activity is independent of Eos-derived microparticles and a proliferation-inducing ligand (APRIL), respectively. Using a multicellular in vitro system designed to resemble the native MM niche, SCs and Eos were shown to have non-redundant roles in their support of MM cell growth. Whereas SCs induce MM cell proliferation predominantly through the secretion of IL-6, Eos stimulate growth of these malignant cells via an IL-6-independent mechanism. Taken together, our study demonstrates for the first time a role for Eos in the pathology of MM and suggests that therapeutic strategies targeting these cells may be beneficial.

Axon cap morphology of the sea robin (Prionotus carolinus): Mauthner cell is correlated with the presence of "signature" field potentials and a C-type startle response.

Studies on the Mauthner cell (M-cell) of goldfish, Carassius auratus, have facilitated our understanding of how sensory information is integrated in the hindbrain to initiate C-type fast startle responses (C-starts). The goldfish M-cell initial segment/axon hillock is surrounded by a composite axon cap consisting of a central core and a peripheral zone covered by a glial cell layer. The high resistivity of the axon cap results in "signature" field potentials recorded on activation of the M-cell, allowing unequivocal physiological identification of the M-cell and of its feedback and reciprocal inhibitory networks that are crucial in ensuring that only one M-cell is active and that it fires only once. Phylogenetic mapping of axon cap morphology to muscle activity patterns and behavior predicts that teleost fishes that have a composite axon cap, like that of the goldfish, will perform C-start behavior with primarily unilateral muscle activity. We have chosen to study these predictions in the northern sea robin, Prionotus carolinus, a percomorph fish. Although sea robins have a very different phylogenetic position, body form, and habitat compared with the goldfish, they display the correlation of axon cap morphology to physiology and C-start behavior. Differences in response parameters suggest some evolutionary trade-offs in sea robin C-start behavior compared with that of the goldfish, but the correlations in morphology, physiology, and behavior are common features of both otophysan and nonotophysan teleosts. The M-cell will continue to provide an unprecedented opportunity to study the evolution of a neural circuit in the context of behavior.