Mid-regional pro-adrenomedullin predicts poor outcome in non-selected patients admitted to an intensive care unit.

Background Mortality risk and outcome in critically ill patients can be predicted by scoring systems, such as APACHE and SAPS. The identification of prognostic biomarkers, simple to measure upon admission to an intensive care unit (ICU) is an open issue. The aim of this observational study was to assess the prognostic value of plasma mid-regional pro-adrenomedullin (MR-proADM) at ICU admission in non-selected patients in comparison to Acute Physiology and Chronic Health Evaluation II (APACHEII) and Simplified Acute Physiology Score II (SAPSII) scores. Methods APACHEII and SAPSII scores were calculated after 24 h from ICU admission. Plasma MR-proADM levels were measured by TRACE-Kryptor on admission (T0) and after 24 h (T24). The primary endpoint was intra-hospital mortality; secondary endpoint was length of stay (LOS). Results One hundred and twenty-six consecutive non-selected patients admitted to an ICU were enrolled. Plasma MR-proADM levels were correlated with LOS (r=0.28; p=0.0014 at T0; r=0.26; p=0.005 at T24). Multivariate analysis showed that T0 MR-proADM was a significant predictor of mortality (odds ratio [OR]: 1.27; 95% confidence interval [95%CI]: 1.03-1.55; p=0.022). Receiver operating characteristic curves analysis revealed that MR-proADM on ICU admission identified non-survivors with high accuracy, not inferior to the one of APACHEII and SAPSII scores (area under the curve [AUC]: 0.71; 95%CI: 0.62-0.78; p=0.0002 for MR-proADM; AUC: 0.71; 95%CI: 0.62-0.79; p<0.0001 for APACHEII; AUC: 0.8; 95%CI: 0.71-0.87; p<0.0001 for SAPSII). Conclusions Our findings point out a role of MR-proADM as a prognostic tool in non-selected patients in ICUs being a reliable predictor of mortality and LOS and support its use on admission to an ICU to help the management of critically ill patients.

Recurrence of hepatocellular carcinoma after liver transplantation: an update.

Liver transplantation is the only curative alternative for selected patients with hepatocellular carcinoma (HCC) who are not eligible for resection and/or with decompensated cirrhosis. According to Milan criteria the 5-year survival rate is 70-85%, with a recurrence-free survival of 75%. However, HCC recurrence rate after liver transplantation remains a significant problem in the clinical practice. The prognosis in patients with HCC recurrence is poor. The treatment of choice for HCC recurrence is surgery, but it seems that a systemic treatment based on combination of an mTOR inhibitor with sorafenib can be used. Data on safety and efficacy are limited, clinical monitoring is necessary. The aim of this review is to underline the main concerns, pitfalls and warnings for these patients.

Assessment of treatment response in hepatocellular carcinoma: a review of the literature.

Hepatocellular carcinoma (HCC) has a high incidence all over the world. Even if the primary end point of treatment of HCC is survival, radiological response could be a surrogate end point of survival, and could have a key role in clinical management. Since 1950 several radiological response criteria have been applied; however, it was not until 2000 that specific criteria for HCC were introduced by the European Association for the Study of the Liver (EASL), and these were then standardized in 2010 with the development of the modified Response Evaluation Criteria for Solid Tumors (mRECIST) for HCC. The purpose of this brief review is to compare data in literature regarding the application and the performance of mRECIST in clinical practice, and to discuss unclear and open issues.

KPC - 3 Klebsiella pneumoniae ST258 clone infection in postoperative abdominal surgery patients in an intensive care setting: analysis of a case series of 30 patients.

BACKGROUND: Abdominal surgery carries significant morbidity and mortality, which is in turn associated with an enormous use of healthcare resources. We describe the clinical course of 30 Intensive Care Unit (ICU) patients who underwent abdominal surgery and showed severe infections caused by Klebsiella pneumoniae sequence type (ST) 258 producing K. pneumoniae carbapenemase (KPC-Kp). The aim was to evaluate risk factors for mortality and the impact of a combination therapy of colistin plus recommended regimen or higher dosage of tigecycline. METHODS: A prospective assessment of severe monomicrobial KPC-Kp infections occurring after open abdominal surgery carried out from August 2011 to August 2012 in the same hospital by different surgical teams is presented. Clinical and surgical characteristics, microbiological and surveillance data, factors associated with mortality and treatment regimens were analyzed. A combination regimen of colistin with tigecycline was used. A high dose of tigecycline was administered according to intra-abdominal abscess severity and MICs for tigecycline. RESULTS: The mean age of the patients was 56.6 ± 15 and their APACHE score on admission averaged 22.72. Twenty out of 30 patients came from the surgical emergency unit. Fifteen patients showed intra-abdominal abscess, eight anastomotic leakage, four surgical site infection (SSI) and three peritonitis. The overall crude ICU mortality rate was 40% (12 out of 30 patients). Twelve of the 30 patients were started on a combination treatment of high-dose tigecycline and intravenous colistin. A significantly lower mortality rate was observed among those patients compared to patients treated with approved dose of tigecycline plus colistin. No adverse events were reported with high doses of tigecycline. CONCLUSIONS: Critically-ill surgical patients are prone to severe post-surgical infectious complications caused by KPC-Kp. Timely microbiological diagnosis and optimizing antibiotic dosing regimens are essential to prevent worse outcomes. Further studies and well-controlled clinical trials are needed to define the optimal treatment of infections by KPC-Kp and, more generally, carbapenem-resistant bacteria.

Allergy to Polyethilenglicole of Anti-SARS CoV2 Vaccine Recipient: A Case Report of Young Adult Recipient and the Management of Future Exposure to SARS-CoV2.

The main contraindication to the anti-SARS CoV2 vaccine is an anaphylactic reaction to a vaccine component. The need to vaccinate allergic people who are at higher risk can be of public health interest and this report shows a case of an allergic reaction to PEG of a HCW who had received the first dose of anti-SARS CoV2 vaccine. For 5 h after the administration of the vaccine, she had the appearance of erythematous spots on the face and neck, and a feeling of a slurred mouth and hoarseness. In order to treat the event, she was administered 8 mg intravenous dexamethasone, 1 vial intravenous chlorphenamine maleate, 250 mL intravenous 0.9% NaCl, and conventional oxygen therapy (2 L/min) with complete resolution of the suspected adverse drug reaction. According to the contraindication to the cutaneous test for this patient, BAT was used for further investigations. The patient who suffered the adverse reaction to the COVID-19 vaccine and other five allergic patients who did not report any adverse reaction after the vaccination were tested. There was a significant activation of the vaccine-reactive patient's basophils with 14.79 CD203chigh% at the concentration of 0.2 mg/mL, while other patients were negative. People who have a confirmed reaction to a vaccine component should undergo further investigation to discover other possible cross-reactions and select the right vaccine to immunize them.

Second line systemic therapies for hepatocellular carcinoma: Reasons for the failure.

Hepatocellular carcinoma (HCC) is the main cause of death in patients with cirrhosis, with an increasing incidence worldwide. Sorafenib is the choice therapy for advanced HCC. Over time several randomized phase III trials have been performed testing sunitinib, brivanib, linifanib and other molecules in head-to-head comparison with Sorafenib as first-line treatment for advanced-stage HCC, but none of these has so far been registered in this setting. Moreover, another feared vacuum arises from the absence of molecules registered as second-line therapy for patients who have failed Sorafenib, representing an urgent unmet medical need. To date all molecules tested as second-line therapies for advanced hepatocellular carcinoma, failed to demonstrate an increased survival compared to placebo. What are the possible reasons for the failure? What we should expect in the near future?

Relationship between background cancer pain, breakthrough pain, and analgesic treatment: a preliminary study for a better interpretation of epidemiological and clinical studies.

BACKGROUND: The different operational definitions of breakthrough cancer pain (BTcP) has generated unclear epidemiological data. METHODS: A consecutive sample of patients was categorized on the basis of their background pain intensity, background analgesic treatment, and the presence of BTcP. RESULTS: A total of 265 patients were surveyed; 117 patients had background pain and 91 patients presented peaks of pain intensity distinguishable from background pain. Of 117 patients with background pain, 49 patients were re-assessed after optimization of background analgesia (T1) within a mean of 8.2 days. Pain intensity significantly decreased in comparison with values recorded at admission (p < 0.0005); 75.5% of these patients had BTcP episodes, with a significant decrease in the number BTcP episodes in comparison with T0 (p < 0.0005). The mean BTcP intensity was significantly lower in comparison with T0 (p < 0.0005). Finally, the mean duration of untreated BTcP episodes decreased significantly in comparison with T0 (p = 0.016). After optimization of analgesic therapy, most patients with moderate or severe background pain receiving opioids for moderate pain, patients with moderate or severe pain receiving strong opioids, and patients with moderate or severe pain receiving no opioids moved to the group of patients with mild pain receiving strong opioids. The difference was significant (p = 0.022). CONCLUSION: Patients having good pain control after optimization of the analgesic regimen may have a decrease in number, intensity, and duration of BTcP, although the general prevalence of BTcP remains unchanged.

Treatment of hepatocellular carcinoma: present and future.

Hepatocellular carcinoma is a major health problem. It is the sixth most common cancer worldwide and the third most common cause of cancer-related death. Despite the availability of several treatment opportunities, diagnosis is still made in an advanced phase, limiting application of most therapeutic choices that currently are based on the Barcelona Clinic Cancer Liver Classification and include surgical resection, orthotopic liver transplantation and ablative methods for very early and early disease, arterial chemoembolization for intermediate stages and systemic therapy with sorafenib for advanced hepatocellular carcinoma. Thanks to novel advancements in knowledge of molecular pathogenesis of this tumor, many new systemic agents and locoregional treatments are in different stages of clinical development and they represent an important promise of further improvements in patients' survival.

Survival of patients with hepatocellular carcinoma (HCC) treated by percutaneous radio-frequency ablation (RFA) is affected by complete radiological response.

BACKGROUND: Radio-frequency ablation (RFA) has been employed in the treatment of Barcelona Clinic Liver Cancer (BCLC) early stage hepatocellular carcinoma (HCC) as curative treatments. AIM: To assess the effectiveness and the safety of RFA in patients with early HCC and compensated cirrhosis. METHODS: A cohort of 151 consecutive patients with early stage HCC (122 Child-Pugh class A and 29 class B patients) treated with RFA were enrolled. Clinical, laboratory and radiological follow-up data were collected from the time of first RFA. A single lesion was observed in 113/151 (74.8%), two lesions in 32/151 (21.2%), and three lesions in 6/151 (4%) of patients. RESULTS: The overall survival rates were 94%, 80%, 64%, 49%, and 41% at 12, 24, 36, 48 and 60 months, respectively. Complete response (CR) at 1 month (p<0.0001) and serum albumin levels (p = 0.0004) were the only variables indipendently linked to survival by multivariate Cox model. By multivariate analysis, tumor size (p = 0.01) is the only variable associated with an increased likehood of CR. The proportion of major complications after treatment was 4%. CONCLUSIONS: RFA is safe and effective for managing HCC with cirrhosis, especially for patients with HCC ≤3 cm and higher baseline albumin levels. Complete response after RFA significantly increases survival.