Diabetes and COVID-19: The potential role of mTOR.

Diabetes is the most frequent comorbidity among patients with COVID-19. COVID-19 patients with diabetes have a more severe prognosis than patients without diabetes. However, the etiopathogenetic mechanisms underlying this more unfavorable outcome in these patients are not clear. Probably the etiopathogenetic mechanisms underlying diabetes could represent a favorable substrate for a greater development of the inflammatory process already dysregulated in COVID-19 with a more severe evolution of the disease. In the attempt to shed light on the possible etiopathogenetic mechanisms, we wanted to evaluate the possible role of mTOR (mammalian Target Of Rapamycin) pathway in this context. We searched the PubMed and Scopus databases to identify articles involving diabetes and the mTOR pathway in COVID-19. The mTOR pathway could be involved in this etiopathogenetic mechanism, in particular, the activation and stimulation of this pathway could favor an inflammatory process that is already dysregulated in itself, while its inhibition could be a way to regulate this dysregulated inflammatory process. However, much remains to be clarified about the mechanisms of the mTOR pathway and its role in COVID-19. The aim of this review is to to understand the etiopathogenesis underlying COVID-19 in diabetic patients and the role of mTOR pathway in order to be able to search for new weapons to deal with this disease.

Risk of invasive fungal infections among patients treated with disease modifying treatments for multiple sclerosis: a comprehensive review.

Introduction: Disease modifying treatments are commonly used in the treatment of multiple sclerosis. As different opportunistic infections have been reported, concerns are also raised regarding the risk of invasive fungal infections.Areas covered: Both clinical trials and observational studies on safety and efficacy of diseases modifying treatment for multiple sclerosis were reviewed and data regarding the occurrence of invasive fungal infections were reported. Papers evaluating the following drugs were reviewed: rituximab, ocrelizumab, alemtuzumab, fingolimod, natalizumab, dimethyl fumarate, interferon, glatiramer acetate, cladribine, teriflunomide.Expert opinion: Overall, the occurrence of invasive fungal infections was low, with most infective events reported among patients treated with monoclonal antibodies and fingolimod. Aspergillosis and cryptococcal meningitidis were the most representative fungal infections. Although not common, these infections may be difficult to diagnose and their fatality rate is often high. For this reason, screening protocols for fungal infections must be implemented in the clinical practice when managing patients with MS.

COVID-19, SARS and MERS: are they closely related?

BACKGROUND: The 2019 novel coronavirus (SARS-CoV-2) is a new human coronavirus which is spreading with epidemic features in China and other Asian countries; cases have also been reported worldwide. This novel coronavirus disease (COVID-19) is associated with a respiratory illness that may lead to severe pneumonia and acute respiratory distress syndrome (ARDS). Although related to the severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS), COVID-19 shows some peculiar pathogenetic, epidemiological and clinical features which to date are not completely understood. AIMS: To provide a review of the differences in pathogenesis, epidemiology and clinical features of COVID-19, SARS and MERS. SOURCES: The most recent literature in the English language regarding COVID-19 has been reviewed, and extracted data have been compared with the current scientific evidence about SARS and MERS epidemics. CONTENT: COVID-19 seems not to be very different from SARS regarding its clinical features. However, it has a fatality rate of 2.3%, lower than that of SARS (9.5%) and much lower than that of MERS (34.4%). The possibility cannot be excluded that because of the less severe clinical picture of COVID-19 it can spread in the community more easily than MERS and SARS. The actual basic reproductive number (R0) of COVID-19 (2.0-2.5) is still controversial. It is probably slightly higher than the R0 of SARS (1.7-1.9) and higher than that of MERS (<1). A gastrointestinal route of transmission for SARS-CoV-2, which has been assumed for SARS-CoV and MERS-CoV, cannot be ruled out and needs further investigation. IMPLICATIONS: There is still much more to know about COVID-19, especially as concerns mortality and its capacity to spread on a pandemic level. Nonetheless, all of the lessons we learned in the past from the SARS and MERS epidemics are the best cultural weapons with which to face this new global threat.

Anastomotic strictures in colorectal surgery: treatment with endoscopic balloon dilation.

The incidence of anastomotic stricture following colorectal surgery has increased in recent years. This complication is observed in 2-5% of all operated patients and is probably due to the greater number of low anastomoses performed with surgical staplers. We observed 31 patients with postoperative stricture, arising from one to nine months post-surgery. All patients had been treated for colorectal cancer and underwent endoscopy either during routine follow-up or for symptoms of stenosis. In 16 patients (group A) the stricture diameter was less than 4 mm and the patients had symptoms attributable to partial bowel obstruction. In the remaining 15 patients (group B), who had difficult bowel movements, the stricture diameter ranged from 4 to 8 mm. All patients were treated with endoscopic dilation using achalasia balloons. The results were considered good when the post-dilation anastomosis diameter achieved was at least 13 mm, fair when it was 9-12 mm and poor when it was less than 9 mm. The short term results (3 weeks) were good in 27 patients (87.2%), fair in 3 patients (9.6%), and poor in 1 patient (3.2%). After several unsuccessful dilations, the latter was treated by surgery. Follow-up at 3-4 months of the remaining 30 patients revealed good results in 20 (66.6%), fair in 6 (20%), and poor in 4 (13.3%). In 1 of these 4 patients, cancer recurrence was observed and a new surgical resection was performed. In 2 patients a self-expandable metal stent was inserted for 4-6 weeks, with satisfactory results. In 1 patient a biodegradable polydioxanone stent was inserted with good results after 6 months. Follow-up at 3-4 months showed good results in 25 patients. After 38 months, cancer recurrence in the area of the anastomosis was observed in 1 patient, who was treated surgically. Endoscopic dilatation should be considered the first therapeutic approach in case of anastomotic strictures, as it is immediately effective, repeatable, and does not preclude surgery if this should become necessary.

Endoscopic treatment of difficult choledocholithiasis.

Common bile duct stones can be treated with normal endoscopic techniques. Where stones cannot be removed due to their size or number or due to stenosis of the common bile duct, a plastic stent can be inserted, enabling rapid drainage of bile. At the three-month check-up complete removal of the stones was found in 41 (85.4%) of the 48 patients with difficult choledocholithiasis. In the remaining 7 patients (14.6%), the stent in any case resulted in clinical improvement. A permanent stent was necessary in 4 patients, enabling safe drainage with no complications. The use of endoscopy for stent placement was effective in all our cases of difficult coledocholithiasis without any complications.

Endoscopic manometry of the sphincter of Oddi: its usefulness for the diagnosis and treatment of benign papillary stenosis.

BACKGROUND: Endoscopic manometry is considered useful to identify dysfunction of the sphincter of Oddi (SO) and to predict in which patients good results can be expected after endoscopic sphincterotomy, but this has not been definitively demonstrated. METHODS: Endoscopic manometry of the SO was used in a group of 30 patients with benign papillary stenosis (BPS), in comparison with 30 control subjects. During endoscopic manometry an intravenous bolus of cholecystokinin octapeptide was given to 12 patients and to 10 controls. In 24 BPS patients endoscopic sphincterotomy was performed. RESULTS: No significant differences were observed between controls and patients with regard to median values of SO basal (20 and 21.5 mmHg) and peak pressure (123 and 126 mmHg), wave amplitude (100 mmHg), frequency (4 waves/min), and propagation of the common bile duct/duodenum gradient (12.5 and 12.1 mmHg). In two BPS patients a paradoxic response to CCK-OP was observed. Endoscopic sphincterotomy, performed in 24 BPS patients (17 with SO basal pressure less than 40 mmHg and 7 with more than 40 mmHg), gave good results in 23, without any complication. No differences were observed in the results of the endoscopic sphincterotomy among patients with basal pressure more than 40 mmHg and those with less than 40 mmHg. CONCLUSIONS: On the basis of this study, manometric data do not seem helpful for diagnosis of BPS or to discriminate which patients can be treated with endoscopic sphincterotomy.

[Peroperative endoscopic papillotomy in a patient with an abdominal aortic aneurysm and biliary calculi]. / Papillotomia endoscopica peroperatoria in paziente con aneurisma dell'aorta addominale e calcolosi biliare.

The authors report a case of abdominal aortic aneurysm associated with biliary tract lithiasis. The need to simultaneously treat both diseases is stressed. A technique which involves endoscopy during open surgery in order to prevent contamination is illustrated. The technique used together with other manoeuvres is part of a methodology aiming to broaden indications to the treatment of abdominal diseases associated with vascular diseases, limiting at the same time the risks of prosthetic infection.

[Extracorporeal lithotripsy and endoscopy in the treatment of pancreatic lithiasis]. / La litotrissia extracorporea e l'endoscopia nel trattamento della litiasi pancreatica.

The decompression of the pancreatic duct with the extraction of stones by endoscopy is now recognized as an effective method for the treatment of some forms of chronic pancreatitis. The limits of this methodology are strictly linked to the morphology of the pancreatic duct and/or to the size, morphology and number of stones. The association of endoscopy with the ESWL often allows to overcome these limits. A case of lithiasis of the Wirsung in a patient affected by C.P. successfully treated associating endoscopy to ESWL is reported.

[Lipoma of the colon. Apropos of a case report]. / Il lipoma del colon. A proposito di un'osservazione.

Lipoma of the large intestine is a rare, benign tumor. The clinical findings and the diagnostic studies are analysed and a case of giant submucosal colonic lipoma removed by colonoscopy is reported. Colonoscopic removal of submucosal lipomas is recommended, while the necessity of a surgical treatment in presence of intussusception or subserosal lipomas is confirmed.

[Endoscopic insertion of a prosthesis in the palliative treatment of tumors of the head of the pancreas]. / L'apposizione di protesi per via endoscopica nel trattamento palliativo dei tumori della testa del pancreas.

The Authors report their experience of biliary endoscopic endoprosthesis placement in 42 patients for palliative treatment of carcinoma of the pancreatic head. The morbidity, the mortality and the duration of hospitalization are considerably less than with surgical biliodigestive anastomosis. The mean survival is almost the same in both cases.

[Intestinal polyposis in children. Description and differential diagnosis of 2 cases]. / Poliposi intestinale in età pediatrica. Descrizione e diagnosi differenziale di due casi.

The case of a 21-month-old girl with lymphoid nodular hyperplasia and the case of a 9-year-old girl with familial adenomatous polyposis are described. Both patients presented rectal bleeding. A defect of secretory IgA was found in the first patient. In both cases diagnosis was based on medical history, barium enema with aircontrast technique, colonscopy, and endoscopic biopsy. Differential diagnosis and diagnostic procedures in these two diseases are discussed.

Endoscopic manometry of the sphincter of Oddi in patients with and without juxtapapillary duodenal diverticula.

The motor activity of the sphincter of Oddi (SO) has been evaluated, by endoscopic manometry, in 48 subjects, 8 with and 40 without duodenal juxtapapillary diverticula. All values were expressed in mm Hg, taking duodenal pressure as zero reference. In subjects with diverticula the SO basal pressure was 14.1 +/- 4.3 mm Hg, peak pressure was 52.3 +/- 17.2 mm Hg, and wave height was 39.75 +/- 14.19 mm Hg; in subjects without diverticula these values were 31.2 +/- 8.9 mm Hg, 93.2 +/- 21.3 mm Hg, and 68.17 +/- 25.86, respectively. The difference was statistically significant (P less than 0.001 for basal and peak pressure; P less than 0.002 for wave height). Wave frequency was not significantly different in controls (4.99 +/- 1.17/min) and in subjects with diverticula (4.98 +/- 1.13/min). These findings seem to indicate that in patients with diverticula the SO is insufficient or dysfunctioning . The insufficiency of the SO and a reflux of bacteria from the duodenum into the bile duct could play a major role in the formation of stones in patients with diverticula. The same mechanism could be responsible for duodenopancreatic reflux and possible pancreatic lesion.

Effects of ethanol on the sphincter of Oddi: an endoscopic manometric study.

The effects of ethanol, given either intragastrically or intravenously, on the sphincter of Oddi was evaluated by endoscopic manometry. In 12 subjects intragastric ethanol (150 ml of 32%) was given over 10 minutes. In five control subjects saline solution (150 ml of 0.9%) was given intragastrically instead of ethanol. In five other subjects ethanol was infused intravenously (6 ml/kg of 10%) for 36 minutes. Ethanol given intragastrically produced a significant inhibitory effect on sphincter of Oddi pressure. Peak pressure fell from a control value of 75.7 +/- 26.35 mmHg to 39 +/- 15.39 mmHg (p less than 0.001) at 35 minutes. Basal pressure fell from a control value of 30.17 +/- 19.47 mmHg to 11.83 +/- 6.35 mmHg (p less than 0.01) at 35 minutes. Wave height fell from a control value of 41.33 +/- 15.4 mmHg to 27.16 +/- 11.25 mmHg (p less than 0.02) at 35 minutes. No effects on sphincter of Oddi wave frequency were observed. No significant modifications of sphincter motor activity were observed after intragastric saline infusion. Ethanol given intravenously also produced an appreciable inhibitory effect on sphincter of Oddi pressure, without affecting its wave frequency.

Endoscopic removal of foreign bodies in the large bowel.

Endoscopic removal of foreign bodies from the intestinal tract is an extremely useful method. In our series, foreign bodies passing down from the upper intestinal tract were removed endoscopically from the rectum and colon of 13 patients. No complications were observed. It can be concluded that endoscopy is a simple, safe and effective method which, in many cases, avoids surgical procedures.

Endoscopic sphincterotomy: indications and results.

Endoscopic sphincterotomy (ES) is a simple, effective and remarkably safe method of treatment of choledocholithiasis and papillary stenosis. In this series, ES was technically successful in 255 (86.1 per cent) of 296 patients in whom it was attempted. Forty-nine of the successful cases had papillary stenosis complicated by pain, cholangitis and/or jaundice in patients after cholecystectomy; 205 had choledocholithiasis, of whom 164 had a cholecystectomy and 41 were poor surgical risks and did not have cholecystectomy. One patient had a tumour of the ampulla of Vater. ES has been performed as an emergency in 16 subjects because of severe septic cholangitis in 11 and acute biliary pancreatitis in 5. Of the 205 patients with choledocholithiasis, spontaneous passage of calculi after ES occurred in 151 cases (73.6 per cent), and instrumental extraction of stones was possible in 44 (21.5 per cent); 10 patients (4.9 per cent) had residual stones and required surgery. In this series the overall success rate of ES in removing common bile duct stones was 82 per cent in 238 cases; in the patients with benign papillary stenosis ES was successful in relieving symptoms and biochemical cholestasis in 72 per cent of 57 cases. Complications occurred in 18 cases (7 per cent): cholangitis in 4 (1.6 per cent) and haemorrhage in 14 (5.4 per cent). Two patients (0.8 per cent) with acute bleeding following ES died; in one of these surgery had been performed to arrest the haemorrhage, but the patient died 3 days after operation of hepatorenal failure. The other complications were treated conservatively without mortality.