Allocation of scarce critical care resources during public health emergencies: which ethical principles support decision making.

Aim: To investigate whether and how ten ethical principles are mentioned within documents on critical care resources allocation during public health emergencies. Materials and Methods: We conducted a search of documents con-cerning critical resources allocation during public emergencies publicly available from Google and two specific international websites, up to November 2020. Each document was analyzed by two independent reviewers to assess whether a reference to any of the 10 key ethical principles indicated by the Northern Italy Ethical Committee could be found in the documents. Cohen's K statistic was used. Results: We obtained 34 documents, of which 19 were allocation frameworks, 15 crisis standards of care, 4 clinical triage protocol, 3 clinical guidelines and 2 public health emergency response plans. The principles most frequently mentioned as important for decision-making was "number of lives saved", followed by "transparency", "equity", "respect of person and their autonomy". The most cited tiebreakers were "younger first/life cycle" and "lottery". Conclusions: All documents aim to protect the life and health of the largest number of people and should be objective, ethical, transparent, applied equitably, and be publicly disclosed. It is plausible that short- and long-term prognostic tools can help allocate critical resources, but it remains strong that the decision-making process must be guided by a multi-principle ethical model that is not always easy to apply.

Role of interventional radiology in pregnancy complicated by placenta accreta spectrum disorder: systematic review and meta-analysis.

OBJECTIVE: To evaluate the potential benefit of interventional radiology (IR) in improving the outcome of women undergoing surgery for a placenta accreta spectrum (PAS) disorder. METHODS: MEDLINE, EMBASE and CINAHL databases were searched for studies comparing outcomes of women with a prenatal diagnosis of PAS who underwent an IR procedure before surgery vs those who did not, using a robust collection of terms relating to PAS. The primary outcome was intraoperative estimated blood loss (EBL). Secondary outcomes were the number of transfused units of packed red blood cells (PRBC), fresh frozen plasma (FFP), platelets and cryoprecipitate, operation time, length of hospital stay, EBL ≥ 2.5 L, PRBC transfused ≥ 5 units, surgical complications, bladder or ureteral injury, relaparotomy, infection, disseminated intravascular coagulation, and complications related to endovascular catheter placement. Only studies reporting on the incidence of, or the mean difference in, the observed outcomes in women affected by a PAS disorder who had vs those who did not have an IR procedure before surgery were considered for inclusion. All outcomes were explored in the overall population of women with a prenatally diagnosed PAS disorder and in those undergoing hysterectomy. Quality assessment of each included study was performed using the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool. The GRADE methodology was used to assess the quality of the body of retrieved evidence. RESULTS: Fifteen studies (958 women with PAS) were included. In women who underwent IR before surgery, compared with those who did not, mean EBL (mean difference (MD), -1.02 L; 95% CI, -1.60 to -0.43 L; P < 0.001) and the risk of EBL ≥ 2.5 L (odds ratio (OR), 0.18; 95% CI, 0.04-0.78; P = 0.02) were significantly lower. There was no significant difference between the two groups in the other outcomes explored. On subgroup analysis of pregnancies complicated by PAS undergoing hysterectomy, EBL (MD, -0.68 L; 95% CI, -1.24 to -0.12 L; P = 0.02) and the number of transfused FFP units (MD, -1.66; 95% CI, -2.71 to -0.61; P = 0.02) were significantly lower in women who had an endovascular IR procedure compared with controls. Furthermore, women undergoing IR had a significantly lower risk of EBL ≥ 2.5 L (OR, 0.10; 95% CI, 0.02-0.47; P = 0.004). Overall, complications related to the placement of an endovascular catheter occurred in 5.3% (95% CI, 2.6-8.9; I2 , 65.3%) of pregnancies undergoing IR. Overall quality of evidence, as assessed by GRADE, was very low. CONCLUSIONS: The current available data provide encouraging evidence that IR procedures may be associated with lower EBL and need for transfusion in pregnancies undergoing surgery for a PAS disorder. However, given the overall very low quality of the evidence, further large studies are needed in order to confirm the beneficial role of IR in improving the outcome of these women. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Biomolecular basis related to inflammation in the pathogenesis of endometrial cancer.

OBJECTIVE: Endometrial cancer (EC) is a complex gynecological neoplasm with several clinical, histopathological and genetic features. Different hormonal, metabolic and biochemical axes are involved in pathogenesis. Obesity is a well-known risk factor for this disease and the role of local and systemic effects of adipose tissue, especially in the promotion of subclinical chronic inflammation, is an important issue. Indeed, inflammation is related to the pathogenesis of different tumors, including EC. This review aims to remark the role of obesity and inflammation in the pathogenesis of EC cancer through an exploration of the current literature. MATERIALS AND METHODS: We performed a comprehensive review of the literature through a PubMed search using key words and including English language papers looking at this topic. RESULTS: Only few authors analyzed the role of inflammatory cytokines released by adipose tissue in visceral abdominal fat depots. Tumor Necrosis Factor-α, Interleukin-6, Interleukin-1 Receptor Antagonist, Nuclear Factor-kB, Leptin, Adiponectin and C Reactive Protein were studied for cancer risk prediction models, risk stratification or targeted therapies. Furthermore, genetic studies evaluated the effect of inflammatory cytokines secreted by visceral adipocytes in the modulation of angiogenesis and signaling pathways such as PI3K/AKT/mTOR, that result altered in the pathogenesis of EC. CONCLUSIONS: The identification of inflammatory biomarkers released by adipose tissue, in the pathogenesis of EC, could be useful in improving diagnostic accuracy, identifying targets of therapy, suggesting useful lifestyle behaviors. A deeper knowledge of the genetic background of alterations in inflammatory pathway genes could better define the population exposed to a higher susceptibility to EC due to genetic polymorphisms. Future studies are needed to better understand this field.

4 × 40-Gb/s TWDM PON downstream transmission over 42 km and 64-way power split using optical duobinary signals and an APD-based receiver.

We demonstrate downstream transmission of a four-channel 40-Gb/s-per-channel time- and wavelength-division-multiplexed PON over a 42-km, 64-split fiber plant using optical duobinary modulation. At 1550 nm, we obtain a reach of 0-26 km or 16-42 km using two dispersion-precompensation values.

Effectiveness of a multipurpose observation unit: before and after study.

BACKGROUND: The clinical efficacy of multipurpose observation units has not been assessed in comparative studies. A study was undertaken to analyse the effects of the adoption of clear criteria of admission, clinical pathways and time limits together with the strengthening of clinical supervision and dedicated staff on the performance of a short observation unit (SOU). METHODS: In the period from 1 January to 26 March 2007, the rates of SOU utilisation, length of observation, consumption of resources during observation (diagnostic tests and specialist consultations), rates of hospitalisation and adverse events were measured. Reattendances at the emergency department (ED) within 3 months of discharge were also analysed. Patients admitted to the SOU during the same period in 2006 acted as controls. RESULTS: Compared with 2006, more patients were admitted to the SOU from the ED (8.8% vs 4.5%, p<0.01) where they had spent less time (mean (SD) 13.8 (11.6) h vs 23.0 (13.4) h, p<0.01). Despite the reduction in the length of stay, case mix standardised rates of hospitalisation were not significantly increased (28.9% vs 26.2%). Consultations and radiological investigations were reduced (32.4% vs 40.2%, p<0.05; and 34.1% vs 45.3%, p<0.01, respectively). Adverse events during the observation period or after hospitalisation were exceptionally rare. The short observation of intestinal obstruction, upper gastrointestinal bleeding without endoscopy, chronic obstructive pulmonary diseases, pneumonia or acute heart failure gave questionable benefits since they had high rates of hospitalisation. During the 3 months after discharge from the SOU, fewer patients returned to the ED (16.3% vs 27.2% for all causes, p<0.01; 9.3% vs 14.4% for related causes, p<0.05) and hospitalisation was necessary in fewer cases (1.7% vs 4.3% for all causes, p<0.05) while re-admissions to the SOU remained unchanged (8.7% vs 8.2%, p = NS). CONCLUSION: Brief observation in the ED draws a clear benefit from proper organisation and the adoption of standardised clinical pathways.

Steroid treatment in active Crohn's disease: a comparison between two regimens of different duration.

BACKGROUND: Steroids are highly effective in active Crohn's disease; clinical relapse following steroid withdrawal, however, is frequent. We used two steroid regimens of different duration in order to compare their efficacy in inducing and maintaining clinical remission. METHODS: Seventy patients with active Crohn's disease were treated with methylprednisolone 40 mg/day i.m. for 3 weeks and then with two different regimens of tapering dosage: one for a further 4 weeks and another for a further 12 weeks. RESULTS: Steroid therapy induced remission within 3 weeks in 91% of the whole group of patients; at the end of each protocol remission rates were 85% of patients in the group treated for the shorter period and 87% of those treated for the longer period (difference 2%, CI = -14 to 18, P = NS); remission rates within 6 months after stopping steroids were 53% and 37% respectively (difference 16%, CI = -9 to 41, P = NS). CONCLUSIONS: No significant differences were found between the two regimens. Multiple courses of steroid treatment in the previous 3 years and a short time interval following previous steroid treatment seem to be risk factors for relapse.

Zinc supplementation restores plasma concentrations of zinc and thymulin in patients with Crohn's disease.

The aim of this work was to evaluate whether oral supplementation with zinc sulphate (ZnSO4) could restore thymic endocrine function in patients with Crohn's disease who showed decreased plasma concentrations of zinc and active thymulin, a zinc-dependent thymic hormone. Twenty-seven patients in clinical remission were randomly assigned to receive, for 3 months, one of the following treatments: 60 mg/day ZnSO4; 200 mg/day ZnSO4 or placebo. Plasma thymulin activity and zinc concentrations significantly increased only in patients treated with 200 mg/day ZnSO4. Lymphocyte subpopulations, within the range of normality before zinc supplementation, were unaffected by any of the administered treatments. In conclusion, low plasma concentrations of zinc and thymulin in Crohn's disease patients were restored by the administration of high doses of zinc.

Comparison of scintigraphy with indium-111 leukocyte scan and ultrasonography in assessment of X-ray-demonstrated lesions of Crohn's disease.

The aim of this study was to compare the results obtained with an indium-111 scan with those obtained with less expensive and harmless ultrasonography to evaluate the location and inflammatory activity of Crohn's disease. Thirty-one patients previously studied with x-ray underwent abdominal 111In scans and ultrasonography (US). Sensitivity and specificity of US in detecting lesions seen with 111In scan were 77% and 92.8%, respectively. Sensitivity and specificity of 111In scan in detecting x-ray-defined lesions were 69.2% and 92.7%; the figures for US were 73% and 93.3%, respectively. Considering the evaluation of disease activity, ultrasonographic bowel wall thickness was significantly related to scintigraphic intensity of emission (r = 0.75 P < 0.01). Our experience suggests that US provided information about the location and inflammatory activity of lesions similar to that obtained from 111In scan.

Interleukin 1 beta (IL-1 beta) release from fresh and cultured colonic mucosa in patients with ulcerative colitis (UC).

Interleukin-1, a cytokine produced by macrophages and other tissue cells, has a major role in inflammatory and immunological responses. Increased levels of IL-1 activity have been reported in experimental colitis and in patients with active Crohn's disease (CD) and ulcerative colitis (UC). IL-1 beta release from fresh and cultured colonic biopsies and IL-1 beta plasma concentrations was determined in 15 patients with active UC, 16 with UC in remission and 10 normal control subjects. Biopsies, taken at colonoscopy were weighed, washed in 1 ml of 0.9% sodium chloride solution and then cultured for 24 h in 10% fetal calf serum/RPMI. IL-1 beta activity was determined by ELISA KIT (Cystron Biotechnology) in plasma samples, washing solution and the incubation medium. Very low levels of IL-1 beta were detected only in 3 plasma samples, all from active patients. Significantly more IL-1 beta was released from fresh and cultured colonic mucosa obtained from patients with UC in remission compared to normal mucosa (p less than 0.01). Furthermore, specimens from active UC released significantly more IL-1 beta than those from patients in remission (p less than 0.01). In conclusion, IL-1 may play an important role in mediating the inflammatory response in UC.

Influence of steroid treatment's duration in patients with active Crohn's disease.

Steroids are very useful drugs in the treatment of active Crohn's disease (CD), but clinical relapses after steroid withdrawal may be very high. We investigated the efficacy of two steroid regimens of different duration in inducing remission and in maintaining it after drug suspension. Patients with active CD were randomly assigned to scheme A, lasting 7 weeks (27 patients), or to scheme B, lasting 15 weeks (27 patients). Remission rates at the end of the treatment were 81% for scheme A and 85% for scheme B. Relapse rates at 6 months after stopping the treatment were 50% (11 patients) and 52% (12 patients), respectively. Remission rates seem not to be influenced by the duration of the treatment, but patients recently treated with steroids showed a higher relapse rate if they received the short-duration treatment.

Placebo-controlled trial of oral 5-ASA in relapse prevention of Crohn's disease.

Treatment of Crohn's disease (CD) in clinical remission is still a debated issue. Previous studies have shown a high risk of relapse for patients with CD in clinical remission (CDAI less than 150) but with some abnormally high laboratory parameters as well as a possible beneficial role of low-dosage steroid treatment in this group of patients. Furthermore, good results have been reported on the efficacy of 5-aminosalicylic acid (5-ASA) in moderately active CD. In our study we verified the efficacy of a slow-release oral 5-ASA preparation in preventing relapses in a group of patients in clinical remission but with raised laboratory parameters. Forty-four patients were randomized in a double-blind manner to receive either 5-ASA (2 g/day) or placebo for four months. Location of disease and previous steroid treatment were similar in both groups. One patient in the 5-ASA group discontinued the drug because of uterine bleeding. During the study period, 13 of 22 placebo-treated patients and 11 of 21 5-ASA-treated patients relapsed (corrected chi square = NS). Considering the location of disease, three of 10 patients in the 5-ASA group and six of nine patients in the placebo group with ileal CD relapsed (therapeutic gain with 5-ASA: 36.6%; 95% allowance for error from -6% to 79.2%). Moreover, in seven patients with ileal CD who remained in remission, we found a statistically significant decrease in alpha 1 acid glycoprotein and C-reactive protein from the second month of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Optimum dosage of 5-aminosalicylic acid as rectal enemas in patients with active ulcerative colitis.

5-Aminosalicylic acid (5-ASA), the active moiety of sulphasalazine (SASP), was given as a rectal enema to patients with mild to moderate distal ulcerative colitis to determine the minimum effective dosage. A double blind study was carried out using enemas containing 1, 2, or 4 g or 5-ASA or placebo for a one month treatment period. One hundred and thirteen patients with ulcerative colitis attending our outpatient clinic volunteered to participate. Clinical, sigmoidoscopic, and histological assessments were carried out at the beginning of the study and after 15 and 30 days of treatment. All patients who received 5-ASA enemas showed significantly better results than those who received a placebo enema (p less than 0.001) but no difference was detected among the patients receiving differing concentrations of 5-ASA. This study suggests that 1 g 5-ASA (in a 100 ml enema) is a sufficient dosage for patients with a mild to moderate attack of ulcerative colitis.

Scavenger effect of sulfasalazine, 5-aminosalicylic acid, and olsalazine on superoxide radical generation.

The in vitro antioxidant capacity of sulfasalazine (SASP), its metabolites (SP, 5-ASA), and olsalazine (OAZ), was studied by evaluating their effects on superoxide (O2-.) production. Assay systems were the xanthine-xanthine oxidase (X/XOD) reaction and phorbol myristate acetate (PMA)-activated polymorphonuclear leukocytes (PMNs), using the cytochrome c (cyt-c) reduction assay and a luminol-dependent chemiluminescence method. 5-ASA, SASP, and OAZ showed a dose-dependent scavenger effect in both O2-. generating systems, 5-ASA being the most powerful (greater than 50% of inhibition in the PMNs system and greater than 70% in the X/XOD system at 10 microM concentration). SP had an inhibitory effect only in the PMNs system but did not modify the activity of xanthine oxidase, thus excluding a scavenger action. These data suggest that the scavenger effect of 5-ASA, SASP, and OAZ may be an important mechanism of action.

Bronchopulmonary involvement in ulcerative colitis.

We report two cases of pulmonary involvement in ulcerative colitis. The first patient, a 37-year-old woman, had bilateral basal bronchiectasis full of mucopurulent secretion, with a marked improvement of pulmonary function and roentgenographic appearance after a conservative approach. The second patient had severe pulmonary fibrosis of autoimmune nature and died owing to a pulmonary infection. In the second patient, a sulfasalazine reaction as an etiologic factor was excluded, while in the first this possibility seemed unlikely. Therefore, we take these two cases as examples of the extraintestinal manifestations of ulcerative colitis.

Levels of zinc and thymulin in plasma from patients with Crohn's disease.

Levels of zinc in plasma from patients with Crohn's disease were significantly lower than those of sex and age matched controls. We also measured the level of plasmic thymulin, a hormone released by the thymus gland, which in its active form binds one zinc molecule. The zinc unbound form of thymulin is biologically inactive and its level in the blood is a very sensitive marker of even marginal zinc deficiency. Levels of active thymulin were significantly reduced in plasma from patients with Crohn's disease, whereas plasma concentrations of the inactive form was higher than in controls. The in vitro addition of zinc ions restored thymulin activity in plasma from patients with Crohn's disease, and induced the disappearance of the inactive form. These findings suggest the existence of a zinc dependent alteration regarding the biological function of thymic hormones in patients with Crohn's disease. Such a defect might explain some of the immunological abnormalities observed in these pathological conditions.

Topical treatment with 5-aminosalicylic in distal ulcerative colitis by using a new suppository preparation. A double-blind placebo controlled trial.

Sixty-two patients with ulcerative colitis localised to the distal sigmoid colon and rectum (less than 20 cm) entered the trial. Thirty-two were treated with 5-ASA 500 mg suppositories (Asacol) 3 times a day for 1 month while 30 received a placebo given in the same regime. Clinical, sigmoidoscopic and histological assessment was carried out before, after 15 days and after 1 month of treatment. At the end of the study 5-ASA suppositories showed significantly better results in all the parameters recorded than placebo (p less than 0.01). There were no unwanted effects related to the use of suppositories. This treatment should therefore be offered as a first choice for patients with distal rectosigmoiditis.

Role of rectal formulations: enemas.

Clinical experience with mesalazine enemas in the treatment of ulcerative colitis is reviewed. After rectal administration, plasma mesalazine levels remain low, and 15% of the administered dose is recovered in the urine. Enemas containing 2 and 4 g of mesalazine have been shown to be effective, safe, and well tolerated by patients with mild and moderate ulcerative colitis. Patients who cannot tolerate sulfasalazine and patients who do not respond to other treatments have been successfully treated with mesalazine enemas. Suppositories of mesalazine are more suitable for patients with disease confined to the distal region of the colon, whereas mesalazine enemas should be used in patients with more extensive disease. Mesalazine enemas have also been used for maintenance therapy in ulcerative colitis.