Identifying Recurrence Risk Factors in CT-Confirmed Acute Appendicitis in Adults Managed Non-operatively During the COVID-19 Pandemic.

BACKGROUND/OBJECTIVE:  Acute appendicitis (AA) is predominantly managed with appendectomy, but can be treated non-operatively, leading to a high risk of recurrence. Non-operative management has been more common since the COVID-19 pandemic affected the feasibility of performing surgery. This case-control study analyzed non-operatively managed patients in order to identify clinical and radiological factors associated with recurrence risk.  Methods: Over 12 months, 48 adults with CT-proven AA managed non-operatively were identified, and followed up for at least six further months to assess them for recurrence (readmission to hospital more than 14 days after discharge and after symptom resolution, requiring treatment for appendicitis). Clinical and CT data were collected and a Cox regression survival analysis was performed to produce hazards ratios (HRs). RESULTS:  Of the 48 patients, 12 (25%) experienced a recurrence up until the end of the follow-up period, eight of whom were then treated operatively, and four treated non-operatively. On the univariate analysis, greater recurrence risk was observed in patients with diabetes mellitus, higher heart rate (on admission and maximum value during admission), lower white cell count and neutrophils and appendiceal wall thinning on CT. On the multivariate analysis, diabetes mellitus (HR=7.72, p=0.021) and higher heart rate (HR=1.08, p=0.018) were associated with statistically significant greater recurrence risk. CONCLUSIONS:  Diabetes mellitus and higher heart rate on admission are associated with greater recurrence risk of AA managed non-operatively. No CT findings were associated with statistically significant greater risk. Clinicians should, therefore, consider DM and heart rate when making decisions on appendicitis management, especially during the COVID-19 pandemic but also beyond it.

Assessment and management after corrosive ingestion: when is specialist centre referral needed? A 10-year UK experience.

BACKGROUND: Corrosive ingestion injuries are rare but clinically significant events, potentially associated with high morbidity and mortality. The low volume of cases limits guideline development. We report a 10-year experience of our tertiary centre focusing on cases requiring specialist care. METHODS: All adults treated following corrosive ingestion between 2010 and 2020 were included. Blood results, imaging and endoscopic findings were reviewed. Patients were stratified based on endoscopic findings. Emergency and delayed management was analysed along with short and long-term outcomes. Predictive value of early outcome indicators was investigated. RESULTS: Eighty-one patients were included, with an average follow-up of 5 years. Patients with injuries ≤ Zargar 2A (n = 15) had long-term outcomes similar to the ones with negative endoscopic findings (n = 51). All fifteen patients suffering injuries Zargar ≥ 2B required ITU and four died (26.6%). All deaths occurred within 50 days of ingestion, had Zargar grade ≥ 3 and airway involvement. Five patients (33%) required emergency operations, two of which died. All Zargar ≥ 2B injury survivors (n = 11) developed strictures and/or tracheo-esophageal fistulae (18%), required multiple admissions and prolonged nutritional support; five required delayed resections. Zargar grade ≥ 2B, airway damage, and increased CRP on admission correlated with unfavourable outcomes. CONCLUSION: Corrosive ingestion injuries up to Zargar 2A do not cause long-term sequelae and can be managed locally. Injuries > 2B bear high mortality and will cause sequelae. Early identification of severe injuries and transfer to specialist centres with multidisciplinary ITU, OG, thoracic and ENT expertise is recommended.

A rare case of heterotopic pancreatitis and intestinal malrotation in a COVID-19 positive patient. COVID-19, causative or coincidence?

INTRODUCTION AND IMPORTANCE: Heterotopic pancreas (HP) is defined as the presence of pancreatic tissue without anatomical and vascular continuity with the main body of the pancreas. HP typically remains asymptomatic, however complications such as acute pancreatitis can arise. Gastrointestinal involvement with coronavirus disease 2019 (COVID-19) is not uncommon and there are reported cases of associated pancreatitis. CASE PRESENTATION: A 31-year-old male presented to the Emergency department (ED) with a 3-day history of right iliac fossa pain. The patient was found to have COVID-19 and a planned laparoscopic appendectomy was later converted to a midline laparotomy when a mass close to the duodeno-jejunal (DJ) flexure was identified. Following a hand-sewn anastomosis the patient made a good post-operative recovery. Histology illustrated the presence of heterotopic pancreatic tissue within the small bowel with underlying fat necrosis typical of acute pancreatitis. Follow-up radiology supported the intraoperative finding of intestinal malrotation. CLINICAL DISCUSSION: Rarely the combined presence of intestinal malrotation and HP in patients has been noted. Heterotopic pancreatitis can present in a multitude of ways and it is a difficult diagnosis to make pre-operatively. Emerging literature documents the potential presentation of COVID-19 with acute pancreatitis. The expression of angiotensin-converting enzyme 2 (ACE2) receptors on the pancreas is believed to play a role. CONCLUSION: This is the first documented case of heterotopic pancreatitis with intestinal malrotation in a COVID-19 positive patient. We hypothesise that the COVID-19 infection contributed to the heterotopic pancreatitis.

Trans-thoracic versus retropleural approach for symptomatic thoracic disc herniations: comparative analysis of 94 consecutive cases.

PURPOSE: The authors illustrate their results in the surgical treatment of symptomatic thoracic disc herniations (TDHs) by comparing the traditional open to the less invasive retropleural lateral approaches. METHODS: Retrospective review of 94 consecutive cases treated at a single Institution between 1988 and 2014. Fifty-two patients were males, 42 females, mean age was 53.9 years. Mean follow-up was 46.9 months (12-79 months). 33 patients were diagnosed with a giant thoracic disc herniation (GTDH). Upon admission, the most common symptoms were: motor impairment (91.4%, n = 86), neuropathic radicular pain with VAS > 4 (50%), bladder and bowel dysfunction (57.4% and 41.4% respectively) and sensory disturbances (29.7%). The surgical approach was based upon level, laterality and presence or absence of calcified lesions. RESULTS: Decompression was performed in 7 cases via a thoraco-laparo-phrenotomy and in 87 cases via an antero-lateral thoracotomy. Out of the latter cases, 49 (56%) were trans-thoracic trans-pleural approaches (TTA) and 38 (44%) were less invasive retropleural approaches (MIRA). At follow-up, there were 59.5% neurologically intact patients according to the McCormick Scale, while 64.8% and 67% had no bladder or bowel dysfunction respectively. Complications occurred in 24 patients (25.5%). Pulmonary complications were the commonest (12.7%) with pleural effusion being significantly more common in patients treated with TTA compared to MIRA (20% vs 5.2%: X2 4.13 P:0.042). Severe post-operative neuralgia (VAS 7-10) was also significantly more frequent in the TTA group (22.4% vs 2.6% X2 7.07 p 0.0078). CONCLUSIONS: MIRA is a safe and effective technique to obtain adequate TDH decompression and is associated with lower morbidity compared to TTA.

Effects of Growth Conditions and Cultivar on the Content and Physiochemical Properties of Arabinoxylan in Barley.

The present study aims to evaluate the effect of the growth conditions and the cultivar on the total and water-extractable (W-E) arabinoxylan (AX) in barley. For this purpose, nine barley varieties from two different years were analyzed. The total AX content ranged from 5.97 to 8.98 wt % d.m., while the W-E AX ranged from 0.06 to 0.35 wt % d.m. The W-E AX molecular properties were characterized by high-pressure size exclusion chromatography (HPSEC)-triple detector array (TDA). The molecular weight was between 2.3 × 105 and 12.6 × 105 Da, the polydispersity was between moderate and broad (1.1 < Mw/Mn < 4.3), and the conformation was a stiff semiflexible coil (0.5 < α < 1.3). The results indicate that the year influences the content of total AX and W-E AX and some molecular characteristics of W-E AX, such as its polydispersity and its conformation. Finally, the results demonstrated that the W-E AX can be used as an index of the malting attitude of barley because it positively correlates with germinative energy and kernel dimension.

Effect of Growth Conditions and Genotype on Barley Yield and ß-Glucan Content of Kernels and Malt.

This study was conducted to evaluate the effect of growth conditions and genotype on the barley yield and ß-glucan content of grain and malt. Total and water-extractable (W-E) ß-glucans and their molecular and structural properties were analyzed in nine 2-row barley varieties and corresponding malts. The total ß-glucan content of barley is not influenced by year or by the cultivar, while the grain yield and W-E ß-glucan content are significantly influenced by the year. Barley W-E ß-glucans have a molecular weight between 1.0 × 105 and 4.0 × 105 Da and a random coil conformation. ß-Glucan levels in malt are significantly lower than in barley, and neither the total nor the W-E ß-glucans are influenced by environmental factors or genetic aspects. W-E ß-glucans are mainly composed of fractions with Mw values below 1.0 × 105 Da. In conclusion, the molecular characterization of ß-glucans could represent a powerful tool to understand their role in the brewing process.

Validation of a high-performance size-exclusion chromatography method to determine and characterize ß-glucans in beer wort using a triple-detector array.

Beer wort ß-glucans are high-molecular-weight non-starch polysaccharides of that are great interest to the brewing industries. Because glucans can increase the viscosity of the solutions and form gels, hazes, and precipitates, they are often related to poor lautering performance and beer filtration problems. In this work, a simple and suitable method was developed to determine and characterize ß-glucans in beer wort using size exclusion chromatography coupled with a triple-detector array, which is composed of a light scatterer, a viscometer, and a refractive-index detector. The method performances are comparable to the commercial reference method as result from the statistical validation and enable one to obtain interesting parameters of ß-glucan in beer wort, such as the molecular weight averages, fraction description, hydrodynamic radius, intrinsic viscosity, polydispersity and Mark-Houwink parameters. This characterization can be useful in brewing science to understand filtration problems, which are not always explained through conventional analysis.

Methionine adenosyltransferase α2 sumoylation positively regulate Bcl-2 expression in human colon and liver cancer cells.

Ubiquitin-conjugating enzyme 9 (Ubc9) is required for sumoylation and inhibits apoptosis via Bcl-2 by unknown mechanism. Methionine adenosyltransferase 2A (MAT2A) encodes for MATα2, the catalytic subunit of the MATII isoenzyme that synthesizes S-adenosylmethionine (SAMe). Ubc9, Bcl-2 and MAT2A expression are up-regulated in several malignancies. Exogenous SAMe decreases Ubc9 and MAT2A expression and is pro-apoptotic in liver and colon cancer cells. Here we investigated whether there is interplay between Ubc9, MAT2A and Bcl-2. We used human colon and liver cancer cell lines RKO and HepG2, respectively, and confirmed key finding in colon cancer specimens. We found MATα2 can regulate Bcl-2 expression at multiple levels. MATα2 binds to Bcl-2 promoter to activate its transcription. This effect is independent of SAMe as MATα2 catalytic mutant was also effective. MATα2 also directly interacts with Bcl-2 to enhance its protein stability. MATα2's effect on Bcl-2 requires Ubc9 as MATα2's stability is influenced by sumoylation at K340, K372 and K394. Overexpressing wild type (but not less stable MATα2 sumoylation mutants) protected from 5-fluorouracil-induced apoptosis in both colon and liver cancer cells. Colon cancer have higher levels of sumoylated MATα2, total MATα2, Ubc9 and Bcl-2 and higher MATα2 binding to the Bcl-2 P2 promoter. Taken together, Ubc9's protective effect on apoptosis may be mediated at least in part by sumoylating and stabilizing MATα2 protein, which in turn positively maintains Bcl-2 expression. These interactions feed forward to further enhance growth and survival of the cancer cell.

Effects of malting on molecular weight distribution and content of water-extractable ß-glucans in barley.

In the beer industry ß-glucans are extensively studied non-starch polysaccharides due to their ability to increase the viscosity of solutions and to form gels. The current study was designed to determine the total and water-soluble ß-glucan contents of barley during malting. Total and water-soluble ß-glucans were analyzed from two different malts that originated from the same barley but varied in germination time from 36h (malt A) to 72h (malt B). Water-soluble ß-glucans were also characterized using high-performance size-exclusion chromatography with triple-detector analysis (HPSEC-TDA) to evaluate the variation in molecular weight distributions, intrinsic viscosity, radius of gyration, Mark-Houwink parameters and polydispersity and thus the overall structural changes during malting. Total ß-glucan content decreased from barley to malt due to the action of ß-glucanase and was greatest in malt B (where 92% of ß-glucans were degraded) which highlights the influence of germination time. ß-Glucan solubility increased during malting, again particularly in malt B, where most of ß-glucans became soluble. The ß-glucanase activity also affected the molecular weight of the polymers which ranged from 298·103g/mol in barley to 293·103 and 218·103g/mol in malts A and B respectively. The molar mass of the most abundant fraction decreased from barley (256·103g/mol) to malt A (112·103g/mol) and malt B (89·103g/mol), again highlighting the effect of the longer germination time. Proceeding from barley to malt, the cumulative molar mass distribution function confirmed that the weight fraction of polymers below 200·103g/mol increased, while the high molecular weight fraction (between 200·103g/mol and 400·103g/mol) decreased. Moreover, the presence of a higher molecular weight fraction (14-16%) beyond 400·103g/mol which does not change during malting was observed. The Mark-Houwink constants α and log k confirmed the random coil conformation of soluble ß-glucans and showed an increase in the compactness of the macromolecules from barley to malts.

Small Molecular Aryl Acetylenes: Chemically Tailoring High-Efficiency Organic Semiconductors for Solar Cells and Field-Effect Transistors.

Over the last two decades, ever increasing interest has been focused on π-conjugated triple-bond-containing systems, namely, (poly)aryl acetylenes, as a very promising class of semiconducting materials, owing to the availability of flexible/efficient synthetic protocols and the new conception of their conformational and steric advantages. In this review, the major design/synthetic strategies used to obtain molecular aryl acetylene semiconductors are discussed. A brief discussion of their key properties as well as their performance in organic field-effect transistors and photovoltaic cell applications is also included.

Polyamine and methionine adenosyltransferase 2A crosstalk in human colon and liver cancer.

Methionine adenosyltransferase (MAT) is an essential enzyme that is responsible for the biosynthesis of S-adenosylmethionine (SAMe), the principal methyl donor and precursor of polyamines. MAT1A is expressed in normal liver and MAT2A is expressed in all extrahepatic tissues. MAT2A expression is increased in human colon cancer and in colon cancer cells treated with mitogens, whereas silencing MAT2A resulted in apoptosis. The aim of the current work was to examine the mechanism responsible for MAT2A-dependent growth and apoptosis. We found that in RKO (human adenocarcinoma cell line) cells, MAT2A siRNA treatment lowered cellular SAMe and putrescine levels by 70-75%, increased apoptosis and inhibited growth. Putrescine supplementation blunted significantly MAT2A siRNA-induced apoptosis and growth suppression. Putrescine treatment (100pmol/L) raised MAT2A mRNA level to 4.3-fold of control, increased the expression of c-Jun and c-Fos and binding to an AP-1 site in the human MAT2A promoter and the promoter activity. In human colon cancer specimens, the expression levels of MAT2A, ornithine decarboxylase (ODC), c-Jun and c-Fos are all elevated as compared to adjacent non-tumorous tissues. Overexpression of ODC in RKO cells also raised MAT2A mRNA level and MAT2A promoter activity. ODC and MAT2A are also overexpressed in liver cancer and consistently, similar MAT2A-ODC-putrescine interactions and effects on growth and apoptosis were observed in HepG2 cells. In conclusion, there is a crosstalk between polyamines and MAT2A. Increased MAT2A expression provides more SAMe for polyamines biosynthesis; increased polyamine (putrescine in this case) can activate MAT2A at the transcriptional level. This along with increased ODC expression in cancer all feed forward to further enhance the proliferative capacity of the cancer cell.

MAT2B-GIT1 interplay activates MEK1/ERK 1 and 2 to induce growth in human liver and colon cancer.

UNLABELLED: Methionine adenosyltransferase 2B (MAT2B) encodes for two variant proteins (V1 and V2) that promote cell growth. Using in-solution proteomics, GIT1 (G Protein Coupled Receptor Kinase Interacting ArfGAP 1) was identified as a potential interacting partner of MAT2B. Here, we examined the functional significance of this interplay. Coimmunoprecipitation experiments examined protein interactions. Tissue expression levels of proteins were examined using immunohistochemistry and western blotting. Expression levels of proteins were varied using transient knockdown or overexpression to observe the effect of alterations in each protein on the entire complex. Direct interaction among individual proteins was further verified using in vitro translated and recombinant proteins. We found both MAT2B variants interact with GIT1. Overexpression of V1, V2, or GIT1 activated mitogen-activated protein kinase kinase 1 (MEK1) and extracellular signal-regulated kinase (ERK), raised cyclin D1 protein level, and increased growth, whereas the opposite occurred when V1, V2, or GIT1 was knocked down. MAT2B and GIT1 require each other to activate MEK1/ERK and increase growth. MAT2B directly interacts with MEK1, GIT1, and ERK2. Expression level of V1, V2, or GIT1 directly influenced recruitment of GIT1 or MAT2B and ERK2 to MEK1, respectively. In pull-down assays, MAT2B directly promoted binding of GIT1 and ERK2 to MEK1. MAT2B and GIT1 interact and are overexpressed in most human liver and colon cancer specimens. Increased expression of V1, V2, or GIT1 promoted growth in an orthotopic liver cancer model, whereas increased expression of either V1 or V2 with GIT1 further enhanced growth and lung metastasis. CONCLUSION: MAT2B and GIT1 form a scaffold, which recruits and activates MEK and ERK to promote growth and tumorigenesis. This novel MAT2B/GIT1 complex may provide a potential therapeutic gateway in human liver and colon cancer. (HEPATOLOGY 2012).

S-adenosyl methionine regulates ubiquitin-conjugating enzyme 9 protein expression and sumoylation in murine liver and human cancers.

UNLABELLED: Ubiquitin-conjugating enzyme 9 (Ubc9) is required for sumoylation and is overexpressed in several malignancies, but its expression in hepatocellular carcinoma (HCC) is unknown. Hepatic S-adenosyl methionine (SAMe) levels decrease in methionine adenosyltransferase 1A (Mat1a) knockout (KO) mice, which develop HCC, and in ethanol-fed mice. We examined the regulation of Ubc9 by SAMe in murine liver and human HCC, breast, and colon carcinoma cell lines and specimens. Real-time polymerase chain reaction and western blotting measured gene and protein expression, respectively. Immunoprecipitation followed by western blotting examined protein-protein interactions. Ubc9 expression increased in HCC and when hepatic SAMe levels decreased. SAMe treatment in Mat1a KO mice reduced Ubc9 protein, but not messenger RNA (mRNA) levels, and lowered sumoylation. Similarly, treatment of liver cancer cell lines HepG2 and Huh7, colon cancer cell line RKO, and breast cancer cell line MCF-7 with SAMe or its metabolite 5'-methylthioadenosine (MTA) reduced only Ubc9 protein level. Ubc9 posttranslational regulation is unknown. Ubc9 sequence predicted a possible phosphorylation site by cell division cycle 2 (Cdc2), which directly phosphorylated recombinant Ubc9. Mat1a KO mice had higher phosphorylated (phospho)-Ubc9 levels, which normalized after SAMe treatment. SAMe and MTA treatment lowered Cdc2 mRNA and protein levels, as well as phospho-Ubc9 and protein sumoylation in liver, colon, and breast cancer cells. Serine 71 of Ubc9 was required for phosphorylation, interaction with Cdc2, and protein stability. Cdc2, Ubc9, and phospho-Ubc9 levels increased in human liver, breast, and colon cancers. CONCLUSION: Cdc2 expression is increased and Ubc9 is hyperphosphorylated in several cancers, and this represents a novel mechanism to maintain high Ubc9 protein expression that can be inhibited by SAMe and MTA.

Surgical treatment of gastric cancer with coexistent abdominal aortic aneurysm. Personal experience and literature review.

BACKGROUND/AIMS: There are great controversies regarding the surgical management of abdominal aortic aneurysm (AAA) with coexistent gastrointestinal cancers. The aim of this study was to report our experience of AAA with concomitant gastric cancer and to compare our results with the literature. METHODOLOGY: From January 1988 to December 2002, six patients with simultaneous diagnosis of AAA and gastric cancer were operated on at the First Department of General Surgery, University of Verona, Italy. The study was completed with the review of the literature data collected by Medline search. RESULTS: The surgical treatment of the cases observed at our Institution, 2 treated by a staged procedure, 2 by synchronous surgery and 2 in which the AAA remained untreated due to the evidence of metastatic disease at laparotomy, were described. Furthermore 47 cases, previously described in literature, 21 who underwent staged surgery, 23 with a synchronous procedure and 3 in which the treatment was limited to the tumor were analyzed. CONCLUSIONS: 1) Synchronous treatment of AAA and gastric cancer is feasible, 2) it can be done with an adequate extent of gastric resection and nodal dissection in the majority of cases, 3) it has a complications rate comparable to the staged procedure.

Endovascular repair of intrathoracic left subclavian artery aneurysm with stent grafts: report of a case and review of the literature.

At present, the standard management of subclavian artery aneurysms is surgical repair. Endovascular treatment of these aneurysms with implantation of a covered stent graft is a relatively new technique that appears to be both feasible and safe. We present the case of a large true aneurysm of the left intrathoracic subclavian artery that was successfully treated with two stent grafts on March 2001. A one-year follow-up CT scan revealed a type 1 secondary endoleak that was successfully treated with a third stent graft. The patient was closely monitored with CT scans that 32 months later confirmed both the patency of the graft and the complete exclusion of the aneurysm, which had decreased in size. At this moment, this is the only case reported in the literature with such a long follow-up but further long-term clinical results will be necessary to fully define the effectiveness of this technique.

Using the angio-seal to achieve hemostasis in prosthetic endovascular surgery: report of three cases.

At least 10% of patients who undergo bilateral aortofemoral bypass are at risk of needing a reoperation for late prosthetic thrombosis because of reduced outflow as the disease progresses. To prevent occlusion of the prostheses, we performed endovascular surgery with transprosthetic access for distal stenosis. We report our experience of using the Angio-Seal with transprosthetic access after angioplasty in three patients who had undergone bilateral aortofemoral bypass. Hemostasis was achieved in all three patients. There were no complications, such as hemorrhage, hematoma, or prosthetic infection, and all three patients were discharged within 24 h. At the 12-, 15-, and 24-month follow-up, none of the patients had any sign of recurrent claudication. Using the Angio-Seal in bilateral aortofemoral bypass provided the means of treating distal stenosis by endovascular surgery with transprosthetic access. This method is both rapid and safe, and may broaden the indications for the endovascular treatment of distal arteriopathies in patients with vascular prostheses.