Public health impact of the COVID-19 pandemic on the emergency healthcare system.

BACKGROUND: The Lombardy region has been the Italian region most affected by the coronavirus disease 2019 (COVID-19) pandemic in 2020. The emergency healthcare system was under deep stress throughout the past year due to the admission of COVID-19 patients to the emergency department (ED) and had to be thoroughly reorganized. METHODS: We performed a retrospective descriptive analysis of patients admitted into the ED recorded in the Lombardy online regional portal called EUOL (Emergenza e Urgenza OnLine). We compared the data registered in the EUOL with the patients admitted to the EDs from 1 January 2019 to 31 December 2019 and from 1 January 2020 to 31 December 2020. RESULTS: The number of admissions to the ED decreased by 32.5% in 2020 compared with 2019, reaching the lowest number in March and April. However, the percentage of patients hospitalized after ED significantly increased in 2020 compared with 2019 (P < 0.0001), reflecting the management of patients with a more severe clinical condition. More patients arrived at the ED by ambulance in 2020 (21.7% in 2020 versus 15.1% in 2019; P < 0.0001), particularly during March and April. CONCLUSIONS: This analysis showed the importance of monitoring the pandemic's evolution in order to treat more critically ill patients, despite a lower number of patients.

Pancreatic injury during AAA repair: a comparison between EVAR and open repair.

OBJECTIVES: Enzymatic pancreatic injury (EPI) in abdominal aortic aneurysm (AAA) treatment has been scarcely studied in the literature. Aim of this work was to compare perioperative EPI in AAA patients treated by endovascular repair (EVAR) or open repair (OR). METHODS: Forty AAA patients consecutively treated with either EVAR (GI, 20 pts) or OR (GII, 20 pts) were prospectively evaluated in terms of epidemiology, comorbidities and technical details. Serum levels of amylase, lipase and pancreatic isoamylase were assessed before treatment (T0), before aortic clamping/endograft deployment (T1), 1, 2, and 6 hours after aortic declamping/endograft deployment (T2, T3, T4) and 24, 48, and 72 hours after the procedure (T5, T6, T7). GI and GII were compared by Mann Whitney test with significance set at p < 0.05. RESULTS: GI patients were significantly older and with higher frequency of preoperative renal insufficiency than GII ones (p = 0.001 and 0.047 respectively). Other characteristics were not significantly different. Pancreatic enzymes values at T0 were within normal parameters in all patients. Total serum amylase was significantly greater at T4 (p = 0.003), T5 (p = 0.010), T6 (p = 0.003), T7 (p = 0.011) and isoamylase at T3 (p = 0.052), T4 (p = 0.037), T5 (p = 0.016) and T6 (p = 0.014) in GII compared with GI. Amylase and isoamylase peak occurred 24 hours after the procedure. Lipase was significantly different in the two groups only in T4 (p = 0.028). No acute pancreatitis occurred in the whole study group. CONCLUSIONS: EVAR significantly reduces EPI compared with OR in the AAA treatment.

Circadian variation in Pseudomonas fluorescens (CHA0)-mediated paralysis of Caenorhabditis elegans.

Abiotic and biotic environmental stressors play a key role in the ecophysiology of most organisms. As the presence and activity of stress-inducing agents vary along the day, organisms that are able to predict these periodic changes are better fit to survive. Caenorhabditis elegans, a soil-dwelling nematode, is subjected to daily changes in its natural environment, and its tolerance to osmotic and oxidative stress varies along the day. Pseudomonas fluorescens strain CHA0 is a soil bacterium that produces a set of secondary metabolites that antagonize phytopathogenic fungi and therefore promote healthy growth of several plant species. Here we show that strain CHA0 is able to affect C. elegans either under growth limiting conditions (i.e., slow-killing) or by rapid paralysis in nutrient replete conditions (fast-killing). Both types of toxicity require the post-transcriptional Gac/Rsm regulatory cascade, and the fast paralytic killing depends strongly on hydrogen cyanide production. The response observed in C. elegans nematodes to fast paralytic killing varies along the day and its sensitivity is higher during the night, at Zeitgeber Time (ZT) 12 (lights off). This behavior correlates well with HCN tolerance, which is higher during the day, at ZT0 (lights on). The innate immune response to P. fluorescens CHA0 might depend on the stress response pathway of C. elegans. The fact that the tolerance varies daily gives further proof of an underlying clock that governs cyclic behavior in C. elegans.

Sucralfate modulates uPAR and EGFR expression in an experimental rat model of cervicitis.

Sucralfate is a drug used in the treatment of gastric and duodenal ulcer; it is cytoprotective and able to increase the bioavailability of several growth factors, modulating the wound healing process. In this study we tested the possible therapeutic effect of Sucralfate in the treatment of ulcerative lesions occurring in uterine cervix; to investigate such effect we used an experimental rat model of cervicitis in which the uPAR and EGFR expression were evaluated. Cervicitis was induced in wild and ovariectomized Wistar female rats by an acetic acid-soaked tampon. The animals were divided into two main groups (4 and 7 days) and Sucralfate was administered topically until the day they were sacrificed. In order to distinguish physiological and drug-induced healing, quantitative and qualitative uPAR and EGFR expression were evaluated by using Western blot and Immunohistochemistry techniques. Western blot analysis demonstrated an increased expression of both receptors after 4 days from wounding in wild and ovariectomized animals. In particular in ovariectomized animals the expression of uPAR and EGFR increased after 4 days while it reduced following the administration of Sucralfate. In wild rats the same was observed for uPAR expression, while EGFR was different; in fact, its expression increased significantly at day 4 in the animals treated with the drug and only at day 7 in those untreated. Immunohistochemistry highlighted a noteworthy epithelial colocalization of EGFR and uPAR after 4 days in the animals treated with Sucralfate. We conclude that Sucralfate can promote the healing of ulcerative cervicitis and moreover, it reduces the normal healing time because of its modulatory property on uPAR and EGFR expression.

Alcoholic pancreatitis: new pathogenetic insights.

Though amply described, alcoholic pancreatitis continues to stir controversy. One of the most debated points is whether it is a chronic disease since onset or progresses to a chronic form after repeated episodes of acute pancreatitis. Histologic studies on patients with pancreatitis have clearly shown that it is chronic since onset and that if necrotic acute pancreatitis develops in an alcoholic, it occurs in a pancreas damaged by chronic lesions. While the possibility cannot be wholly excluded that alcohol-related acute pancreatitis may develop in the absence of chronic lesions, such an occurrence would be rare. In addition to alcoholism, genetic factors play a determinant role in the pathogenesis of the disease. Genetic studies have suggested that in hereditary pancreatitis mutation of the cationic trypsinogen gene and serine peptidase inhibitor, Kazal type 1 (SPINK1) genes mutations of the may have pathogenetic importance; however, studies on alcoholic pancreatitis have produced disappointing results so far.

C-reactive protein in patients on chronic hemodialysis with different techniques and different membranes.

In hemodialysis patients, C-reactive protein (CRP), an acute-phase reactant, is a sensitive and independent marker of malnutrition, anemia, and cardiovascular mortality. The aim of the present study was to evaluate CRP levels in plasma samples from long-term hemodialysis patients on different extracorporeal modalities and dialyzed with different membranes, at baseline and after 6 months. Two hundred and forty-seven patients were recruited in eight hospital-based centers. All patients had been on their dialytic modality for at least 3 months and were prospectively followed in their initial dialytic modality for 6 months. Patients were treated with conventional bicarbonate dialysis (N = 127) or hemodiafiltration (N = 120). Patients treated with conventional bicarbonate dialysis were dialyzed with different membranes: Cuprophane (N = 51), low-flux cellulose modified membrane (N = 37) and synthetic membranes (N = 39). Hemodiafiltration was performed in post-dilution mode with polysulfone (N = 66) and polyacrylonitrile (N = 54) membranes. Analysis of baseline CRP values in the clinically stable patients showed that an unexpectedly high proportion (47%) of the patients had CRP values higher than 5 mg/l (upper limit in normal subjects). The mean +/- S.D. CRP values were significantly higher (P < 0.05) in hemodiafiltration with infusion volumes < 10 l per session (14.6+/-3.1 mg/l) than in standard hemodialysis (5.1 +/- 2.1 mg/l) and hemodiafiltration with infusion volumes > 20 l per session (4.9 +/- 2.1 mg/l). These values did not significantly change after 6 months of follow-up. Concerning the membranes, the highest levels of CRP were observed in patients dialyzed with Cuprophane with a significant increase from 15.1 +/- 3.6 to 21.2 +/- 3.1 mg/l after 6 months (P < 0.05); a significant reduction of CRP levels was observed in patients dialyzed with polysulfone in the same follow-up period (from 13.5 +/- 2.9 to 8.1 +/- 2.4 mg/l; P < 0.05). The CRP increase following low volume HDF can be related to back-filtration of bacterial derived contaminants.; moreover, an important effect on CRP of the hemodialysis membrane is observed and new synthetic membranes can be used to decrease these levels.

Treatment with 1,25-dihydroxyvitamin D3 preserves glomerular slit diaphragm-associated protein expression in experimental glomerulonephritis.

In this study, we investigated the effect of 1,25(OH)2D3 on proteinuria and on the alteration of slit diaphragm-associated proteins induced by anti-Thy 1.1 in Wistar rats. Four groups of animals were studied: group I, anti-Thy 1.1 treated rats; group II, anti-Thy1.1 treated group that at day 2, after the onset of overt proteinuria, started the treatment with 1,25(OH)2D3; group III, normal control rats injected with vehicle alone; group IV, rats that received only 1,25(OH)2D3. At day 2, in group I and II, before the administration of 1,25(OH)2D3, protein excretion was significantly increased when compared to controls. Overt proteinuria was maintained until day 14 in group I whereas in group II protein excretion was significantly reduced from day 3 to day 14. Moreover, treatment with 1,25(OH)2D3 abrogated podocytes injury, detected as desmin expression and loss of nephrin and zonula occludens-1 (ZO-1), two slit diaphragm-associated proteins, and glomerular polyanion staining, that were observed in group I. In conclusion, these results suggest that 1,25(OH)2D3 administrated with a therapeutic regiment may revert proteinuria, counteracting glomerular podocyte injury.

Ring chromosome 5 associated with severe growth retardation as the sole major physical abnormality.

We report on a case of ring chromosome 5 in a 36-month-old girl with severe growth retardation, clinodactyly, mild psychological abnormalities, and normal facial appearance. Endocrine tests showed partial growth hormone deficiency. Cytogenetic investigation failed to demonstrate any apparent microscopic deletion of either short or long arm of chromosome 5 as consequence of ring formation. In 12% of cells examined, the ring was either absent or present in multiple copies. Only 3 previous cases of ring chromosome 5 have been reported in association with short stature of prenatal onset and minor anomalies, without mental retardation.

Treatment of gastroenteropancreatic neuroendocrine tumours with octreotide LAR.

BACKGROUND: Octreotide long acting repeteable (LAR) is a new somatostatin analogue whose activity lasts 28 days. AIM: To assess its therapeutic efficacy, tolerability, and safety in patients with gastroenteropancreatic neuroendocrine tumours. METHODS: A total of 16 patients were studied; 10 patients with carcinoid tumours, three with non-functioning pancreatic tumours, two with Zollinger-Ellison syndrome associated with multiple endocrine neoplasia type 1, and one with glucagonoma were studied. Octreotide LAR was administered intramuscularly at a dose of 20 mg every 28 days for a mean of 10.7 months (range 6-15 months). RESULTS: In carcinoid tumour patients, octreotide LAR normalized bowel movements in nine out of 10 cases, and flushing episodes disappeared in seven out of eight cases. Even in the remaining six patients the symptoms disappeared. In carcinoid tumour patients, urinary 5-hydroxyindoleacetic acid decreased significantly. In the two patients with Zollinger-Ellison syndrome/multiple endocrine neoplasma type 1 and in the patient with glucagonoma, serum gastrin and plasma glucagon, respectively, decreased considerably. Tumour size remained unchanged in 14 out of 16 patients, and increased in the remaining two. No side-effects were observed. CONCLUSIONS: Octreotide LAR appears to have a good therapeutic efficacy, tolerability and safety in the treatment of neuroendocrine tumours. Its effects are similar to those of octreotide and lanreotide. However, because it only needs to be administered once every 28 days, it is preferable in clinical practice.

Endothelization and adherence of leucocytes to nanostructured surfaces.

We analyse the leucocyte and endothelial cell response to polybromostyrene-polystyrene (PS/PBrS) and the poly-n-butylmethacrylate-polystyrene (PnBMA/PS) systems, both in flat form or nanostructured surfaces consisting of nanohills with increasing hill height (13-95nm). Experiments were carried out first with blood leucocytes alone, endothelial cells (of three different types) alone, and finally, using blood cells and endothelized nanosurfaces. Blocking monoclonal antibodies specific for CD11, CD29, CD31, CD54, CD166 were used to analyse whether and to what extent adhesion molecules could be involved in the adherence of both blood leucocytes and endothelial cells to different nanosurfaces. Expression of CD29 (beta-1 integrin), CD54 (ICAM-1) and CD166 (ALCAM) on blood leucocytes was dependent on the hill height, being most prominent with 13nm (PS/PBrS) and 45nm hill (PnBMA/PS) nanosurfaces. Adherence of a human microvascular endothelial cell line and umbilical primary endothelial cells was also related to hill height, being most prominent with 13nm hill height. An indirect correlation was observed between the extent of endothelization and the degree of leucocyte adherence. In cases of low to medium extent of endothelization, the adherence of monocytes and granulocytes was mediated by the expression of CD166, CD29 and CD11a (alpha-L integrin), CD29, CD31 (PECAM-1), respectively. Scanning electron microscopy studies showed the predominant emission of pseudopodia at the holes of the surfaces and the focal contacts with the nanosurfaces. Our studies emphasize the relevance of testing functional properties in co-culture experiments in the development and optimization of nanosurfaces for biomedical application.

Intraocular pressure changes after neodymium-YAG laser capsulotomy in eyes pretreated with timolol.

Sixty eyes undergoing Q-switched neodymium-YAG laser posterior capsulotomy were randomly assigned to pretreatment with either 0.5% timolol maleate or placebo. Half of the eyes in each group underwent capsulotomies performed with six 2-mJ bursts of energy, and the remaining eyes underwent capsulotomies performed with three 4-mJ bursts of energy. There was no significant difference in pressure responses between eyes treated with 2 or 4 mJ. The mean rise in intraocular pressure was significantly less in the timolol-pretreated group one hour after capsulotomy. After four hours, the difference between groups was not significant. Pretreating with timolol did not prevent late pressure rises. Nonpseudophakic eyes were more likely to sustain pressure increases greater than 10 mm than were pseudophakic eyes.

The link of biocompatibility to cytokine production.

Recent studies suggest that chronic inflammation plays a role in the pathogenesis of cardiovascular disease. Cytokines released from jeopardized tissues stimulate the liver to synthesize acute phase proteins, including C-reactive protein (CRP). Baseline levels of CRP in apparently healthy persons or in persons with unstable angina constitute an independent risk factor for cardiovascular events. More recently, it has been suggested that CRP is useful not only as a marker of the acute phase response, but is also involved in the pathogenesis of the disease. CRP may, in fact, directly interact with the atherosclerotic vessels or ischemic myocardium by activation of the complement system, thereby promoting inflammation and thrombosis. Several studies in uremic patients have implicated CRP as a marker of malnutrition, resistance to erythropoietin, and chronic stimulation in hemodialysis. An increased cytokine production secondary to blood interaction with bioincompatible dialysis components has been reported by several studies; interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and mainly IL-6 are the three proinflammatory cytokines involved in the pathogenesis of hemodialysis-related disease. We have provided evidence for the occurrence of high CRP and IL-6 levels in chronic dialytic patients exposed to contaminate dialysate and suggest that backfiltration may induce a chronic, slowly developing inflammatory state that may be abrogated by avoiding backfiltration of contaminate dialysate. Therefore, CRP is implicated as a marker linking bioincompatibility associated with backfiltration and increased cytokine production with a clinical state of chronic inflammation.

Do early symptoms of pancreatic cancer exist that can allow an earlier diagnosis?

Diagnosis of pancreatic cancer is made late, and prognosis remains extremely poor. This study was carried out to investigate whether symptoms exist before pain or jaundice that could suggest pancreatic cancer and favor earlier diagnosis. The study involved 305 patients with confirmed pancreatic cancer and 305 controls. All subjects were interviewed personally at least twice about their clinical history; pancreatic cancer patients were asked about any disturbances before abdominal pain or jaundice. Of the 305 pancreatic cancer patients, 151 (49.5%) had some prior disturbances, 108 (35.4%) 6 months or less before pain or jaundice and 43 (14.1%) more than 6 months before. Among the latter, 14 (4.6% of all patients) had had anorexia and/or early satiety and/or asthenia (7-20 months before pain or jaundice), 11 (3.6%) had disgust for coffee and/or smoking and/or wine (7-20 months before), 14 (4.6%) had diabetes (7-24 months before), and four (1.3%) had acute pancreatitis (8-26 months before). Among the controls, the only reports of these symptoms were two (0.7%) cases of asthenia (4 and 6 years earlier), 22 (7.2%) cases of diabetes (of which only two [0.7%] were diagnosed 7-24 months before the interview), and one (0.33%) case of acute pancreatitis (10 years earlier). Apart from acute pancreatitis, all the other differences between patients and controls were statistically significant. In approximately 15% of patients, disturbances existed more than 6 months before pain or jaundice, which, although not specific, could raise suspicion of the possibility of pancreatic cancer. These disturbances could represent the one current opportunity for an earlier diagnosis in a significant minority of pancreatic cancer patients.

Recurrent conjunctival papilloma causing nasolacrimal duct obstruction.

We treated two patients who had recurrent conjunctival papillomas that invaded the nasolacrimal sac and caused complete canalicular and nasolacrimal duct obstruction. The ophthalmologist should be aware of the possibility of a conjunctival papilloma invading the lacrimal sac when treating patients with conjunctival papillomas. Excision should be complete, and adjunctive therapy such as cryotherapy should be considered to reduce the chance of tumor recurrence.

Combined viable composite grafting and eyelid sharing techniques to prevent blepharoptosis after extensive tumor excision.

Five patients underwent tumor excision involving either the entire upper eyelid and temporal lower eyelid (three patients) or the entire lower eyelid and temporal upper eyelid (two patients), followed by reconstruction with an eyelid sharing procedure combined with viable composite grafting to the upper eyelid and a temporal semicircular flap. None of the five patients developed postoperative blepharoptosis, and all had excellent functional and cosmetic results. Follow-up ranged from 23 to 94 months.

Determination of the normal range of exophthalmometric values for black and white adults.

We used the Hertel exophthalmometer to measure the degree of protrusion in 681 adults, ranging in age from 18 to 91 years. The 327 white and 354 black subjects had no history of orbital or endocrine disease, severe myopia (more than -7 diopters), or buphthalmos. The mean normal protrusion values were 16.5 mm in white men, 18.5 mm in black men, 15.4 mm in white women, and 17.8 mm in black women. Although protrusion values above 21 mm are usually considered abnormal, we found that the upper limits of normal were 21.7 mm for white men, 24.7 mm for black men, 20.1 mm for white women, and 23.0 mm for black women. These differences were statistically significant (P less than .025). No individual had more than 2 mm of asymmetry between eyes.

Surgical treatment of trigeminal schwannomas.

A total of 27 patients with trigeminal schwannoma were treated between 1982 and 1992 at the Neurosurgery Department of Nordstadt Hospital. Twelve cases of solitary schwannoma without any family history or physical stigmata of neurofibromatosis were included and form the basis of this study. There were four women and eight men (mean age 44 years) in this series. Duration of symptoms ranged from 2 months to 6 years. The most frequent symptoms were either pain or numbness of the ipsilateral hemiface. The surgical approach was chosen depending on the tumor type. Tumors that belonged to Type A (five cases), which were predominantly in the middle fossa, were approached using a transsylvian method; Type B (one case), which presented predominantly in the cerebellopontine angle, was operated on via a retrosigmoid suboccipital craniectomy; Type C (five cases), which were dumbbell-shaped extending into both the middle and posterior fossa, were removed via a combined temporal craniotomy-presigmoidal method; and in Type D (one case), in which tumor was primarily extracranial with intracranial extension, an infratemporal extradural approach was undertaken. There was no operative mortality or long-term disability in this series. The follow-up period ranged from 12 to 60 months; during that time magnetic resonance imaging revealed tumor recurrence in two cases after 12 and 48 months, respectively, and these were excised again. An additional 178 cases collected from the world literature are also reviewed and analyzed.

Diagnostic value of plasma chromogranin A in neuroendocrine tumours.

AIM: The aim of this study was to assess the value of plasma chromogranin A (CgA), a protein produced by neuroendocrine cells, in the diagnosis of neuroendocrine tumours. METHODS: Eighty subjects with neuroendocrine tumours were studied. Thirty-four had carcinoids, 21 nonfunctioning endocrine pancreatic tumours, 17 multiple endocrine neoplasia type 1 (MEN 1) (six of these also had gastrinomas), and eight had functioning pancreatic tumours (four gastrinomas, two glucagonomas, two somatostatinomas). Twenty-eight healthy subjects were studied as controls. A fasting plasma sample was obtained from each subject, and CgA plasma levels were measured by the ELISA method using a kit (Dako A/S, Denmark). RESULTS: In control subjects, plasma CgA values were below 5 U/l. Among the patients, 20 of the 34 with carcinoid tumours, 12 of the 21 with nonfunctioning pancreatic tumours, nine of the 17 with MEN 1 (including the six with gastrinomas), and the four gastrinomas of the eight functioning pancreatic tumours, i.e. overall, 45 of the 80 patients (56.3%) had abnormally high CgA values (22-961 U/l). Most of the patients with elevated CgA values, except nine of the 10 with gastrinomas, had multiple liver metastasis. CONCLUSIONS: The results show that the diagnostic value of plasma CgA in neuroendocrine tumours is relatively low; it may be of some interest only in patients with advanced disease and liver metastasis. Gastrinoma seems to be an exception, because in this tumour high CgA values are generally found even in the absence of liver metastasis.

Pancreatic hyperenzymaemia and hypertransaminasaemia in healthy subjects. Report of three cases.

Three healthy subjects, two from Italy and one from the United States, showing a chronic increase in serum pancreatic enzymes and transaminases are described. The enzyme elevations reached very high levels but were not constant; rather, they fluctuated and sometimes returned to normal. Furthermore, tests for non-hepatic diseases that can be accompanied by an increase in serum transaminases, such as coeliac disease, were normal. The intervals between the first finding of the pancreatic hyperenzymaemia and the hypertransaminasaemia and this study ranged from 2 to 6 years (mean 4.3 years), during which the three subjects remained healthy, with no clinical, laboratory or imaging evidence of disease. These data support the conclusion that these increases in enzymes are benign; however, monitoring of these three subjects is already underway. Awareness of this anomaly is important, both to relieve the distress of the persons involved, as well as to avoid the numerous, sometimes invasive, complex and expensive examinations that might otherwise be unnecessarily performed.

Basis for treatment of functioning neuroendocrine tumours.

A general characteristic of GEP endocrine tumours is that vast majority produce and secrete a multitude of peptide hormones and amines. The rarity of these types of tumours, their possible episodic expression and the variable clinical symptoms, are the reasons why patients are often diagnosed late in the advanced stages of the disease. For these reasons, the patients with advanced metastatic disease should be treated aggressively with medical and surgical therapies aimed at reducing both symptoms and complications through strategies that reduce tumour bulk and block hormonal effects. The medical treatment of functioning endocrine tumours of the gastrointestinal tract must be based on the growth properties of the tumour and includes chemotherapy, somatostatin analogs, alpha-interferon alone and associated with somatostatin analogs, chemoembolization and radiolabelled somatostatin analogs. Even if chemotherapy has been basis of therapy for these types of tumours for a long time, it is currently reserved for progressive disease and anaplastic tumours. Biotherapy, with interferon and somatostatin analogs has been demonstrated to have a significant antitumor effect and causes an improvement of symptoms in patients with functioning neuroendocrine tumours. Furthermore, these drugs produce a notable improvement in the quality of life. Radioactive targeting therapy is the most promising new treatment modality for patients who have SST receptor positive tumours.