Blocking Mitophagy Does Not Significantly Improve Fuel Ethanol Production in Bioethanol Yeast Saccharomyces cerevisiae.

Ethanolic fermentation is frequently performed under conditions of low nitrogen. In Saccharomyces cerevisiae, nitrogen limitation induces macroautophagy, including the selective removal of mitochondria, also called mitophagy. Previous research showed that blocking mitophagy by deletion of the mitophagy-specific gene ATG32 increased the fermentation performance during the brewing of Ginjo sake. In this study, we tested if a similar strategy could enhance alcoholic fermentation in the context of fuel ethanol production from sugarcane in Brazilian biorefineries. Conditions that mimic the industrial fermentation process indeed induce Atg32-dependent mitophagy in cells of S. cerevisiae PE-2, a strain frequently used in the industry. However, after blocking mitophagy, no significant differences in CO2 production, final ethanol titers, or cell viability were observed after five rounds of ethanol fermentation, cell recycling, and acid treatment, which is commonly performed in sugarcane biorefineries. To test if S. cerevisiae's strain background influenced this outcome, cultivations were carried out in a synthetic medium with strains PE-2, Ethanol Red (industrial), and BY (laboratory) with and without a functional ATG32 gene and under oxic and oxygen restricted conditions. Despite the clear differences in sugar consumption, cell viability, and ethanol titers, among the three strains, we did not observe any significant improvement in fermentation performance related to the blocking of mitophagy. We concluded, with caution, that the results obtained with Ginjo sake yeast were an exception and cannot be extrapolated to other yeast strains and that more research is needed to ascertain the role of autophagic processes during fermentation. IMPORTANCE Bioethanol is the largest (per volume) ever biobased bulk chemical produced globally. The fermentation process is well established, and industries regularly attain nearly 85% of maximum theoretical yields. However, because of the volume of fuel produced, even a small improvement will have huge economic benefits. To this end, besides already implemented process improvements, various free energy conservation strategies have been successfully exploited at least in laboratory strains to increase ethanol yields and decrease byproduct formation. Cellular housekeeping processes have been an almost unexplored territory in strain improvement. It was previously reported that blocking mitophagy by deletion of the mitophagy receptor gene ATG32 in Saccharomyces cerevisiae led to a 2.1% increase in final ethanol titers during Japanese sake fermentation. We found in two commercially used bioethanol strains (PE-2 and Ethanol Red) that ATG32 deficiency does not lead to a significant improvement in cell viability or ethanol levels during fermentation with molasses or in a synthetic complete medium. More research is required to ascertain the role of autophagic processes during fermentation conditions.

Management of pelvic organ prolapse of ruptured and extruded bladder from a rare complication of vaginal hysterectomy: a case presentation.

BACKGROUND: The prolapse of a ruptured and extruded bladder after vaginal hysterectomy is rare in clinical practice. We report the case of a significant mass that prolapsed from the vagina after a vaginal hysterectomy in a multiparous postmenopausal woman. CASE PRESENTATION: A 67-year old multiparous postmenopausal Chinese woman was found to have a significant mass extruding from the vagina after a vaginal hysterectomy. The mass was a ruptured and everted bladder, and the diagnosis was confirmed after physical and imaging examinations and urethral catheterization. The patient underwent an emergency operation for mass reduction, bladder repair, and partial colpocleisis under general anesthesia. She recovered without prolapse or urinary drainage complications after 35 months of follow-up. CONCLUSIONS: The present case serves as a guide for the management of patients with pelvic organ prolapse. The condition of patients should be carefully evaluated before surgery, and individualized operation should be performed. Careful postoperative follow-up is crucial for the timely exclusion of complications, especially in elderly patients with persistently increased abdominal pressure.

Glucose promotes epithelial-mesenchymal transitions in bladder cancer by regulating the functions of YAP1 and TAZ.

Glucose levels and type 2 diabetes (T2D) are both associated with tumorigenesis and epithelial-mesenchymal transitions (EMTs). EMTs facilitate bladder cancer (BC) metastasis development, but the mechanism by which high-glucose levels promote these EMTs in BC remains unclear. Therefore, we sought to elucidate the mechanism underlying EMT promotion due to increased glucose levels. T24 and UMUC-3 cells were cultured in media containing different glucose concentrations. YAP1, TAZ, GLUT1 and EMT-associated marker expression was analysed via Western blotting and qPCR. BC cell proliferation and invasion were assessed using MTT and Transwell assays, respectively. A xenograft nude mouse model of diabetes was used to evaluate tumour growth and metastasis in vivo. T2D was positively associated with pathologic grade (P = .016) and TNM stage (P < .001) in BC. High glucose triggered BC cell proliferation and invasion in both in vitro and in vivo conditions. High-glucose levels also promoted EMTs in BC cells and increased YAP1 and TAZ expression. YAP1 or TAZ knockdown altered EMT marker expression and decreased GLUT1 expression. Overall, our results suggest that high-glucose levels promote EMTs in BC cells via YAP1 and TAZ regulation. These effector molecules may be promising therapeutic targets for BC cases comorbid with T2D.

Long noncoding RNA LINC00319 regulates ROMO1 expression and promotes bladder cancer progression via miR-4492/ROMO1 axis.

Growing reports indicate that long noncoding RNA (lncRNA) are involved in the regulation of various biological processes of cancer cells. LINC00319 is an ill investigated lncRNA and has been shown to regulate lung cancer, nasopharyngeal carcinoma and ovarian cancer. Nevertheless, its roles in bladder cancer (BCa) remain unclear. In our research, LINC00319 was shown to be an upregulated lncRNA in BCa tissues. LINC00319 expression is negatively correlated with the patient's prognosis. Silencing of LINC00319 suppressed BCa proliferation and invasiveness. In addition, the data indicated LINC00319 was a sponge for miR-4492 and miR-4492 suppressed ROMO1 expression in BCa. Furthermore, our results illustrated miR-4492/ROMO1 axis regulates proliferation, migration, and invasion and LINC00319 exerts oncogenic roles through modulating miR-4492/ROMO1 axis. In sum, this study suggested that LINC00319 acts as oncogenic roles in BCa progression.

Coagulopathy induced by traumatic brain injury: systemic manifestation of a localized injury.

Traumatic brain injury (TBI)-induced coagulopathy is a common and well-recognized risk for poor clinical outcomes, but its pathogenesis remains poorly understood, and treatment options are limited and ineffective. We discuss the recent progress and knowledge gaps in understanding this lethal complication of TBI. We focus on (1) the disruption of the brain-blood barrier to disseminate brain injury systemically by releasing brain-derived molecules into the circulation and (2) TBI-induced hypercoagulable and hyperfibrinolytic states that result in persistent and delayed intracranial hemorrhage and systemic bleeding.

Lactadherin promotes microvesicle clearance to prevent coagulopathy and improves survival of severe TBI mice.

Coagulopathy is common in patients with traumatic brain injury (TBI) and predicts poor clinical outcomes. We have shown that brain-derived extracellular microvesicles, including extracellular mitochondria, play a key role in the development of TBI-induced coagulopathy. Here, we further show in mouse models that the apoptotic cell-scavenging factor lactadherin, given at a single dose of 400 µg/kg 30 minutes before (preconditioning) or 30 minutes after cerebral fluid percussion injury, prevented coagulopathy as defined by clotting time, fibrinolysis, intravascular fibrin deposition, and microvascular bleeding of the lungs. Lactadherin also reduced cerebral edema, improved neurological function, and increased survival. It achieved these protective effects by enhancing the clearance of circulating microvesicles through phosphatidylserine-mediated phagocytosis. Together, these results identify the scavenging system for apoptotic cells as a potential therapeutic target to prevent TBI-induced coagulopathy and improve the outcome of TBI.

von Willebrand factor enhances microvesicle-induced vascular leakage and coagulopathy in mice with traumatic brain injury.

von Willebrand factor (VWF) is an adhesive ligand, and its activity is proteolytically regulated by the metalloprotease ADAMTS-13 (a disintegrin and metalloprotease with thrombospondin type 1 repeat 13). An elevated level of plasma VWF has been widely considered a marker for endothelial cell activation in trauma and inflammation, but its causal role in these pathological conditions remains poorly defined. Using a fluid percussion injury mouse model, we demonstrated that VWF released during acute traumatic brain injury (TBI) was activated and became microvesicle-bound. The VWF-bound microvesicles promoted vascular leakage and systemic coagulation. Recombinant ADAMTS-13 given either before or after TBI reduced the VWF reactivity with minimal influence on VWF secretion. rADAMTS-13 protected the integrity of endothelial cell barriers and prevented TBI-induced coagulopathy by enhancing VWF cleavage without impairing basal hemostasis. Promoting microvesicle clearance by lactadherin had efficacy similar to that of rADAMTS-13. This study uncovers a novel synergistic action between VWF and cellular microvesicles in TBI-induced vascular leakage and coagulopathy and demonstrates protective effects of rADAMTS-13.

Extracellular mitochondria released from traumatized brains induced platelet procoagulant activity.

Coagulopathy often develops soon after acute traumatic brain injury and its cause remains poorly understood. We have shown that injured brains release cellular microvesicles that disrupt the endothelial barrier and induce consumptive coagulopathy. Morphologically intact extracellular mitochondria accounted for 55.2% of these microvesicles, leading to the hypothesis that these extracellular mitochondria are metabolically active and serve as a source of oxidative stress that activates platelets and renders them procoagulant. In testing this hypothesis experimentally, we found that the extracellular mitochondria purified from brain trauma mice and those released from brains subjected to freeze-thaw injury remained metabolically active and produced reactive oxygen species. These extracellular mitochondria bound platelets through the phospholipid-CD36 interaction and induced α-granule secretion, microvesiculation, and procoagulant activity in an oxidant-dependent manner, but failed to induce aggregation. These results define an extracellular mitochondria-induced and redox-dependent intermediate phenotype of platelets that contribute to the pathogenesis of traumatic brain injury-induced coagulopathy and inflammation.

Current state of transfusion in traumatic brain injury and associated coagulopathy.

Traumatic brain injury (TBI)-induced coagulopathy has long been recognized as a significant risk for poor outcomes in patients with TBI, but its pathogenesis remains poorly understood. As a result, current treatment options for the condition are limited and ineffective. The lack of information is most significant for the impact of blood transfusions on patients with isolated TBI and in the absence of confounding influences from trauma to the body and limbs and the resultant hemorrhagic shock. Here we discuss recent progress in understanding the pathogenesis of TBI-induced coagulopathy and the current state of blood transfusions for patients with TBI and associated coagulopathy.

Enhanced perioperative care and decreased cost and length of stay after elective major spinal surgery.

OBJECTIVEThe purpose of this study was to compare total cost and length of stay (LOS) between spine surgery patients enrolled in an enhanced perioperative care (EPOC) pathway and patients receiving traditional perioperative care (TRDC).METHODSAll spine surgery candidates were screened for inclusion in the EPOC pathway. This cohort was compared to a retrospective cohort of patients who received TRDC and a concurrent group of patients who met inclusion criteria but did not receive the EPOC (no pathway care [NOPC] group). Direct and indirect costs as well as hospital and intensive care LOSs were analyzed between the 3 groups.RESULTSTotal costs after pathway implementation decreased by $19,344 in EPOC patients compared to a historical cohort of patients who received TRDC and $5889 in a concurrent cohort of patients who did not receive EPOC (NOPC group). Hospital and intensive care LOS were significantly lower in EPOC patients compared to TRDC and NOPC patients.CONCLUSIONSThe implementation of a multimodal EPOC pathway decreased LOS and cost in major elective spine surgeries.

[Therapeutic effect of tadalafil on lower urinary tract symptoms with erectile dysfunction].

OBJECTIVE: To investigate the therapeutic effect of low-dose tadalafil on BPH-induced lower urinary tract symptoms (LUTS) complicated with ED. METHODS: We randomly assigned 126 patients with BPH-induced LUTS and ED to receive daily administration of tadalafil (5 mg) plus tamsulosin hydrochloride sustained-release capsules (0.2 mg) (treatment group Ⅰ ［T-Ⅰ］, n = 42), tadalafil (5 mg) only (treatment group Ⅱ ［T-Ⅱ］, n = 42) or placebo (control group, n = 42), all for 12 weeks. Before and after 6 and 12 weeks of medication, and at 4 and 8 weeks after drug withdrawal, we recorded and compared the IPSS sub-item scores in the voiding stage and urinary storage symptoms, total IPSS, IIEF-5 scores, and the frequency of sexual activities among the three groups of patients. RESULTS: As for the IPSS sub-item scores in the voiding stage symptoms, T-Ⅰ showed statistically significant differences between any two of the five time points (P < 0.05), but not T-Ⅱ between the baseline and 6-week medication or 8-week withdrawal (P > 0.05), or between 6-week medication and 8-week withdrawal (P > 0.05), nor did the control group among the five time points (P > 0.05). Statistically significant differences were observed between any two of the three groups at 12 weeks of medication and 4 weeks after drug withdrawal (P < 0.05), but not between the T-Ⅱ and control groups at 6 weeks of medication or 8 weeks after withdrawal (P > 0.05). As to the IPSS sub-item scores in the urinary storage symptoms, there were significant differences between any two time points in T-Ⅰ and T-Ⅱ (P < 0.05), but not in the control (P > 0.05), nor between T-Ⅰ and T-Ⅱ at 6 or 12 weeks of medication or at 4 or 8 weeks after drug withdrawal (P > 0.05). With regard to the total IPSS, statistically significant differences were found between any two of the three groups at 6 and 12 weeks of medication and 4 and 8 weeks after drug withdrawal (P < 0.05), but not between 6-week medication and 8-week withdrawal in T-Ⅰ or T-Ⅱ (P > 0.05), nor among the five time points in the control group (P > 0.05). Concerning the IIEF-5 scores, there was no significant difference in the frequency of sexual activities between the three groups （Ｐ>0.05）.There were statistically significant differences between any two of the three groups at 6 weeks of medication and 8 weeks after drug withdrawal (Ｐ<0.05), but not between 6-week medication and 4- or 8-week withdrawal (P > 0.05) or between 4- and 8-week withdrawal (P > 0.05) in T-Ⅰ, nor between 6-week medication and 8-week withdrawal in T-Ⅱ (P > 0.05) or among the five time points in the control (P > 0.05), nor between T-Ⅰ and T-Ⅱ at 12 weeks of medication (P > 0.05) or 4 weeks after drug withdrawal (P > 0.05). CONCLUSIONS: Daily administration of tadalafil at 5 mg can effectively improve the IPSS sub-item scores in the urinary storage symptoms and IIEF-5 scores, with a persistent effect after withdrawal similar to that of its combination with other drugs, and therefore can be recommended for the treatment of BPH-induced LUTS complicated with ED.

Methylprednisolone Therapy in Acute Traumatic Spinal Cord Injury: Analysis of a Regional Spinal Cord Model Systems Database.

BACKGROUND: The objective of this study was to assess the relationship between exposure to methylprednisolone (MP) and improvements in motor function among patients with acute traumatic spinal cord injury (TSCI). MP therapy for patients with TSCI is controversial because of the current conflicting evidence documenting its benefits and risks. METHODS: We conducted a retrospective cohort study from September 2007 to November 2014 of 311 patients with acute TSCI who were enrolled into a model systems database of a regional, level I trauma center. We linked outcomes and covariate data from the model systems database with MP exposure data from the electronic medical record. The primary outcomes were rehabilitation discharge in American Spinal Injury Association (ASIA) motor scores (sum of 10 key muscles bilaterally as per International Standards for Neurological Classification of Spinal Cord Injury, range, 0-100) and Functional Independence Measure (FIM) motor scores (range, 13-91). Secondary outcomes measured infection risk and gastrointestinal (GI) complications among MP recipients. For the primary outcomes, multivariable linear regression was used. RESULTS: There were 160 MP recipients and 151 nonrecipients. Adjusting for age, sex, weight, race, respective baseline motor score, surgical intervention, injury level, ASIA Impairment Scale (AIS) grade, education, and insurance status, there was no association with improvement in discharge ASIA motor function or FIM motor score among MP recipients: -0.34 (95% CI, -2.8, 2.1) and 0.75 (95% CI, -2.8, 4.3), respectively. Adjusting for age, sex, race, weight, injury level, and receipt of surgery, no association with increased risk of infection or GI complications was observed. CONCLUSIONS: This retrospective cohort study involving patients with acute TSCI observed no short-term improvements in motor function among MP recipients compared with nonrecipients. Our findings support current recommendations that MP use in this population should be limited.

Effects of angiotensin-converting enzyme inhibitor, captopril, on bone of mice with streptozotocin-induced type 1 diabetes.

There are contradictory results about the effect of angiotensin-converting enzyme inhibitors (ACEIs) on bone. This study was performed to address the skeletal renin-angiotensin system (RAS) activity and the effects of the ACEI, captopril, on the bone of streptozotocin-induced type 1 diabetic mice. Histochemical assessment on bone paraffin sections was conducted by Safranin O staining and tartrate-resistant acid phosphatase staining. Micro-computed tomography was performed to analyze bone biological parameters. Gene and protein expression were determined by real-time polymerase chain reaction and immunoblotting, respectively. Type 1 diabetic mice displayed osteopenia phenotype and captopril treatment showed no osteoprotective effects in diabetic mice as shown by the reduction of bone mineral density, trabecular thickness and bone volume/total volume. The mRNA expression of ACE and renin receptor, and the protein expression of renin and angiotensin II were markedly up-regulated in the bone of vehicle-treated diabetic mice compared to those of non-diabetic mice, and these molecular changes of skeletal RAS components were effectively inhibited by treatment with captopril. However, treatment with captopril significantly elevated serum tartrate-resistant acid phosphatase 5b levels, reduced the ratio of osteoprotegerin/receptor activator of nuclear factor-κB ligand expression, increased carbonic anhydrase II mRNA expression and the number of matured osteoclasts and decreased transforming growth factor-ß and osteocalcin mRNA expression in the tibia compared to those of diabetic mice. The present study demonstrated that the use of the ACEI, captopril, has no beneficial effect on the skeletal biological properties of diabetic mice. However, this could be attributed, at least partially, to its suppression of osteogenesis and stimulation of osteoclastogenesis, even though it could effectively inhibit high activity of local RAS in the bone of diabetic mice.

Renin inhibition improves ovariectomy-induced osteoporosis of lumbar vertebra in mice.

The skeletal renin­angiotensin system (RAS) is involved in the progression of osteoporosis and the active peptide within the RAS, angiotensin II (ANG II), has deleterious effects on bones. This study was performed to investigate whether suppression of the rate-limiting step of the RAS cascade by the renin inhibitor aliskiren has a benefit on trabecular bone in osteoporotic mice. A postmenopausal osteoporosis model was induced by bilateral ovariectomy. The ovariectomized (OVX) mice were treated with a low (5 mg/kg) or high (25 mg/kg) dose of aliskiren for 6 weeks. Micro-computed tomography was performed to detect trabecular bone parameters of lumbar vertebra and to obtain 3-dimensional (3D) images. Treatment with aliskiren markedly increased bone volume over total volume (p<0.05), trabecular bone number (p<0.05), connectivity density (p<0.05), and bone mineral density (p<0.05) and reduced trabecular bone separation (p<0.05) compared to vehicle-treated OVX mice. Similarly, the 3D images were consistent with the quantitative data that showed aliskiren could markedly reverse the ovariectomy-induced pathological changes of trabecular bone. Thus, this study indicated that the treatment of estrogen-deficient mice with aliskiren could markedly increase bone mass and improve trabecular bone structure, suggesting its potential application in treating postmenopausal osteoporosis.

The constant oxidation state of Earth's mantle since the Hadean.

Determining the evolutionary history of mantle oxygen fugacity (fo2) is crucial, as it controls the fo2 of mantle-derived melts and regulates atmospheric composition through volcanic outgassing. However, the evolution of mantle fo2 remains controversial. Here, we present a comprehensive dataset of plume-derived komatiites, picrites, and ambient mantle-derived (meta)basalts, spanning from ~3.8 Ga to the present, to investigate mantle thermal and redox states evolution. Our results indicate that fo2 of both mantle plume-derived and ambient mantle-derived melts was lower during the Archean compared to the post-Archean period. This increase in the fo2 of mantle-derived melts over time correlates with decreases in mantle potential temperature and melting depth. By normalizing fo2 to a constant reference pressure (potential oxygen fugacity), we show that the fo2 of both the mantle plume and ambient upper mantle has remained constant since the Hadean. These findings suggest that secular mantle cooling reduced melting depth, increasing the fo2 of mantle-derived melts and contributing to atmospheric oxygenation.

MIKC type MADS-box transcription factor LcSVP2 is involved in dormancy regulation of the terminal buds in evergreen perennial litchi (Litchi chinensis Sonn.).

SHORT VEGETATIVE PHASE (SVP), a member of the MADS-box transcription factor family, has been reported to regulate bud dormancy in deciduous perennial plants. Previously, three LcSVPs (LcSVP1, LcSVP2 and LcSVP3) were identified from litchi genome, and LcSVP2 was highly expressed in the terminal buds of litchi during growth cessation or dormancy stages and down-regulated during growth stages. In this study, the role of LcSVP2 in governing litchi bud dormancy was examined. LcSVP2 was highly expressed in the shoots, especially in the terminal buds at growth cessation stage, whereas low expression was showed in roots, female flowers and seeds. LcSVP2 was found to be located in the nucleus and have transcription inhibitory activity. Overexpression of LcSVP2 in Arabidopsis thaliana resulted in a later flowering phenotype compared to the wild-type control. Silencing LcSVP2 in growing litchi terminal buds delayed re-entry of dormancy, resulting in significantly lower dormancy rate. The treatment also significantly up-regulated litchi FLOWERING LOCUS T2 (LcFT2). Further study indicates that LcSVP2 interacts with an AP2-type transcription factor, SMALL ORGAN SIZE1 (LcSMOS1). Silencing LcSMOS1 promoted budbreak and delayed bud dormancy. Abscisic acid (200 mg/L), which enforced bud dormancy, induced a short-term increase in the expression of LcSVP2 and LcSMOS1. Our study reveals that LcSVP2 may play a crucial role, likely together with LcSMOS1, in dormancy onset of the terminal bud and may also serve as a flowering repressor in evergreen perennial litchi.

Contribution of the patient microbiome to surgical site infection and antibiotic prophylaxis failure in spine surgery.

Despite modern antiseptic techniques, surgical site infection (SSI) remains a leading complication of surgery. However, the origins of SSI and the high rates of antimicrobial resistance observed in these infections are poorly understood. Using instrumented spine surgery as a model of clean (class I) skin incision, we prospectively sampled preoperative microbiomes and postoperative SSI isolates in a cohort of 204 patients. Combining multiple forms of genomic analysis, we correlated the identity, anatomic distribution, and antimicrobial resistance profiles of SSI pathogens with those of preoperative strains obtained from the patient skin microbiome. We found that 86% of SSIs, comprising a broad range of bacterial species, originated endogenously from preoperative strains, with no evidence of common source infection among a superset of 1610 patients. Most SSI isolates (59%) were resistant to the prophylactic antibiotic administered during surgery, and their resistance phenotypes correlated with the patient's preoperative resistome (P = 0.0002). These findings indicate the need for SSI prevention strategies tailored to the preoperative microbiome and resistome present in individual patients.

Detecting traumatic brain injury-induced coagulopathy: What we are testing and what we are not.

ABSTRACT: Coagulopathy after traumatic brain injury (TBI) is common and has been closely associated with poor clinical outcomes for the affected patients. Traumatic brain injury-induced coagulopathy (TBI-IC) is consumptive in nature and evolves rapidly from an injury-induced hypercoagulable state. Traumatic brain injury-induced coagulopathy defined by laboratory tests is significantly more frequent than clinical coagulopathy, which often manifests as secondary, recurrent, or delayed intracranial or intracerebral hemorrhage. This disparity between laboratory and clinical coagulopathies has hindered progress in understanding the pathogenesis of TBI-IC and developing more accurate and predictive tests for this severe TBI complication. In this review, we discuss laboratory tests used in clinical and research studies to define TBI-IC, with specific emphasis on what the tests detect and what they do not. We also offer perspective on developing more accurate and predictive tests for this severe TBI complication.

Embolization and Resection of Epidural Spinal Arteriovenous Malformations: Case Report.

BACKGROUND AND IMPORTANCE: Spinal vascular malformations (sVMs) are relatively uncommon, accounting for 5% to 10% of all spinal cord lesions. Spetzler and Kim developed a paradigm to classify sVMs based on a variety of characteristics into 1 of 6 types, including a subcategory for exclusively epidural sVMs. There is a paucity of literature focused on this category, specifically sources describing the clinical manifestation and management of these lesions. CLINICAL PRESENTATION: We report 2 cases of purely epidural spinal arteriovenous fistula, with an emphasis on the radiographic features and combined endovascular and microsurgical treatment. We report 2 patients known to have epidural spinal arteriovenous fistula who underwent both embolization and surgical resection between May 2019 and August 2020 at our institution. Data collected included demographic, clinical, and operative course, including age, sex, medical history, presenting symptoms, and preoperative and postoperative imaging. Both of these patients were managed with a combination of an endovascular approach for embolization of feeding arterial source and surgical exploration/resection. In both cases, no residual vascular malformation was identified, and the patients went on to be symptom free after 6 weeks. CONCLUSION: This report describes the use of a combination of endovascular and surgical approaches to achieve maximal benefit for 2 patients. These cases reinforce the value of a staged multimodal treatment approach in achieving good functional outcomes for patients with these rare and challenging entities.

Efficacy of COVID-19 vaccines in inflammatory bowel disease patients receiving anti-TNF therapy: A systematic review and meta-analysis.

Background and objectives: There are concerns about the serological responses to Coronavirus disease 2019 (COVID-19) vaccines in inflammatory bowel disease (IBD) patients, particularly those receiving anti-TNF therapy. This study aimed to systematically evaluate the efficacy of COVID-19 vaccines in IBD patients receiving anti-TNF therapy. Methods: Electronic databases were searched to identify relevant studies. We calculated pooled seroconversion rate after COVID-19 vaccination and subgroup analysis for vaccine types and different treatments were performed. Additionally, we estimated pooled rate of T cell response, neutralization response, and breakthrough infections in this population. Results: 32 studies were included in the meta-analysis. IBD patients receiving anti-TNF therapy had relatively high overall seroconversion rate after complete vaccination, with no statistical difference in antibody responses associated with different drug treatments. The pooled positivity rate of T cell response was 0.85 in IBD patients receiving anti-TNF therapy. Compared with healthy controls, the positivity of neutralization assays was significantly lower in IBD patients receiving anti-TNF therapy. The pooled rate of breakthrough infections in IBD patients receiving anti-TNF therapy was 0.04. Conclusions: COVID-19 vaccines have shown good efficacy in IBD patients receiving anti-TNF therapy. However, IBD patients receiving anti-TNF have a relatively high rate of breakthrough infections and a low level of neutralization response.