The Italian coronavirus disease 2019 outbreak: recommendations from clinical practice.

Novel coronavirus 2019 is a single-stranded, ribonucleic acid virus that has led to an international pandemic of coronavirus disease 2019. Clinical data from the Chinese outbreak have been reported, but experiences and recommendations from clinical practice during the Italian outbreak have not. We report the impact of the coronavirus disease 2019 outbreak on regional and national healthcare infrastructure. We also report on recommendations based on clinical experiences of managing patients throughout Italy. In particular, we describe key elements of clinical management, including: safe oxygen therapy; airway management; personal protective equipment; and non-technical aspects of caring for patients diagnosed with coronavirus disease 2019. Only through planning, training and team working will clinicians and healthcare systems be best placed to deal with the many complex implications of this new pandemic.

Consecutive episodes of heart and kidney failure in an "otherwise" healthy young man.

BACKGROUND: Acute renal failure is a rare occurrence in a patient with an unremarkable past medical history and should always lead to an in depth clinical study. The occurrence in the same healthy young subject, of consecutive episodes of heart failure and of acute renal failure is an even rarer event and should prompt diagnostic tests and restrict the diagnostic hypotheses. CASE PRESENTATION: We present the case of a 28 year-old man who, while waiting to undergo assessment for a mild chronic kidney disease, was diagnosed with decompensated dilated cardiomyopathy and placed on diuretics and ß-blockers. After few weeks he developed a non oligoanuric acute renal failure with a slight elevation of serum calcium. Renal biopsy proved suggestive for renal sarcoidosis; thus the hypothesis of systemic sarcoidosis with cardiac and renal involvement was possible avoiding further delay in initiation of therapy. CONCLUSIONS: Cardiac sarcoidosis is usually silent but the majority of cases are diagnosed when cardiac symptoms are present in a patient with systemic sarcoidosis. Renal involvement with granulomatous interstitial nephritis is also quite rare and can be an unexpected finding at kidney biopsy. This case highlights the need to evaluate thoroughly clinical problems that do not fit in a specific scenario and emphasizes the importance of performing a kidney biopsy in case of kidney failure of unknown etiology.

In Silico Identification of JMJD3 Demethylase Inhibitors.

In the search for new demethylase inhibitors, we have developed a multistep protocol for in silico screening. Millions of poses generated by high-throughput docking or a 3D-pharmacophore search are first minimized by a classical force field and then filtered by semiempirical quantum mechanical calculations of the interaction energy with a selected set of functional groups in the binding site. The final ranking includes solvation effects which are evaluated in the continuum dielectric approximation (finite-difference Poisson equation). Application of the multistep protocol to JMJD3 jumonji demethylase has resulted in a dozen low-micromolar inhibitors belonging to five different chemical classes. We have solved the crystal structure of JMJD3 inhibitor 8 in the complex with UTX (a demethylase in the same subfamily as JMJD3) which validates the predicted binding mode. Compound 8 is a promising candidate for future optimization as it has a favorable ligand efficiency of 0.32 kcal/mol per nonhydrogen atom.

Benefits of Retroperitoneoscopic Surgery in Pediatric Urology.

PURPOSE OF REVIEW: The aim of this review is to find out the benefits of retroperitoneoscopy for the most common urological diseases in children. RECENT FINDINGS: The emergence of minimally invasive surgery about 20 years ago revolutionized pediatric urology. In this context, laparoscopy and later retroperitoneoscopy were developed and applied to a wide spectrum of urological diseases. Both approaches have since presented benefits and disadvantages that have been documented in various series. The main indications of retroperitoneoscopy are presented, from the classical ablative surgery, like total or partial nephrectomy, to more advanced reconstructive surgery. The success rate is similar to open surgery. However, few comparative studies have been conducted. According to the most recent findings, retroperitoneoscopic surgery in children is feasible and safe if performed by well-trained surgeons. A pediatric urologist would favor the retroperitoneoscopic access to reach the upper urinary tract and the kidney because this is the "natural" way to treat the most common urological pediatric diseases.

Heterogeneity of KRAS, NRAS, BRAF and PIK3CA mutations in metastatic colorectal cancer and potential effects on therapy in the CAPRI GOIM trial.

BACKGROUND: Evidence suggests that metastatic colorectal carcinoma (mCRC) has a high level of intratumor heterogeneity. We carried out a quantitative assessment of tumor heterogeneity for KRAS, NRAS, BRAF and PIK3CA mutations, in order to assess potential clinical implications. PATIENTS AND METHODS: Tumor samples (n = 182) from the CAPRI-GOIM trial of first-line cetuximab + FOLFIRI in KRAS exon-2 wild-type mCRC patients were assessed by next-generation sequencing that allows quantitative assessment of mutant genes. Mutant allelic frequency was normalized for the neoplastic cell content and, assuming that somatic mutations usually affect one allele, the Heterogeneity Score (HS) was calculated by multiplying by 2 the frequency of mutant alleles in neoplastic cells. Therefore, HS virtually corresponds to the fraction of neoplastic cells carrying a specific mutation. RESULTS: The KRAS HS ranged between 12 and 260 with mean value of 87.1 and median value of 84.4, suggesting that in most CRC, the majority of neoplastic cells carry mutant KRAS. Similar findings were observed for NRAS (HS range 35.5-146.7; mean 102.8; median 117.1). In contrast, in BRAF (HS range 17.1-120; mean 54.8; median 54.3) and PIK3CA (HS range 14.3-120; mean 59.5; median 47.3) mutant cases, only a fraction of neoplastic cells seem to carry the mutant allele. The response rate was 70% in KRAS mutant patients with an HS <33 (low KRAS; n = 10) and 45.7% in KRAS HS >33 patients (high KRAS; n = 35); median progression-free survival were 7.97 and 8.37 months, respectively. Low-KRAS tumors had a higher frequency of additional mutations in PIK3CA when compared with high-KRAS (6/10 versus 8/35). CONCLUSIONS: KRAS and NRAS mutations are usually present in the majority of neoplastic cells, whereas BRAF and PIK3CA mutations often affect a limited fraction of transformed cells. Resistance to cetuximab in low-KRAS patients might be driven by the complex mutational profile rather than KRAS mutation load.

Hypertonic saline plus i.v. furosemide improve renal safety profile and clinical outcomes in acute decompensated heart failure: A meta-analysis of the literature.

BACKGROUND: In advanced congestive heart failure (CHF), intravenous (i.v.) inotropic agents, i.v. diuretics, ultrafiltration, and hemodialysis have been shown to not yield better clinical outcomes. In this scenario, the simultaneous administration of hypertonic saline solution (HSS) and furosemide may offer a more effective therapeutic option with a good safety profile. METHODS: Therefore, a meta-analysis was performed to compare combined therapy, consisting of i.v. furosemide plus concomitant administration of HSS, with i.v. furosemide alone for acute decompensated heart failure (ADHF). The outcomes we chose were all-cause mortality, risk of re-hospitalization for ADHF, length of hospital stay, weight loss, and variation of serum creatinine. RESULTS: Based on five randomized controlled trials (RCTs) involving 1,032 patients treated with i.v. HSS plus furosemide vs. 1,032 patients treated with i.v. furosemide alone, a decrease in all-cause mortality in patients treated with HSS plus furosemide was proven [RR = 0.57; 95 % confidence interval (CI) = 0.44-0.74, p = 0.0003]. Likewise, combined therapy with HSS plus furosemide was shown to be associated with a reduced risk of ADHF-related re-hospitalization (RR = 0.51; 95 % CI = 0.35-0.75, p = 0.001). Besides, combined therapy with HSS plus furosemide was found to be associated with a reduced length of hospital stay (p = 0.0002), greater weight loss (p < 0.00001), and better preservation of renal function (p < 0.00001). CONCLUSION: HSS as an adjunct to i.v. furosemide for diuretic-resistant CHF patients led to a better renal safety profile and improved clinical endpoints such as mortality and heart failure-related hospitalizations.

Laparoscopy or retroperitoneoscopy for pediatric patients with adrenal masses?

Minimally invasive approach to the adrenal gland was first reported in 1992. Since then, the experience with the laparoscopic technique for adrenal disease in children has been limited. We report our experience with minimally invasive adrenal surgery in children. Two young girls (2 and 4 years old) with a left adrenal mass were operated using minimally invasive surgery (MIS) in our Unit. Ultrasonography and MRI showed in the oldest a 2 x 3 cm adrenal mass, while in the youngest a 5.5 x 5 cm adrenal tumor was found. According to the pre-existing literature, we approached the smallest lesion via retroperitoneoscopy, and the largest one laparoscopically. The operating time was 110 minutes for retroperitoneoscopy and 75 minutes for laparoscopy. No major intra or postoperative complications occurred. There were no conversions to open surgery. Postoperative hospital stay was 5 days for both patients. In both cases, the anatomo-pathological result was an adenoma. Minimally invasive adrenalectomy is a safe and feasible procedure in children with good results. For lesions smaller than 3-4 cm retroperitonescopy is feasible, while for tumors larger than 5 cm, due to malignancy risk, the laparoscopic approach is indicated. To keep oncologic criteria it is important to avoid tumor rupture and to extract the specimen in an endobag.

Early left ventricular abnormality/dysfunction in obese children affected by NAFLD.

BACKGROUND AND AIMS: Although it is generally accepted that non alcoholic fatty liver disease (NAFLD) is linked to increased risk of cardiovascular disease, the presence of abnormalities in cardiac function among NAFLD children is limited and controversial. Aim of the study was to detect cardiac abnormalities/dysfunction in a paediatric population of NAFLD. METHODS AND RESULTS: Anthropometric, laboratory, cardiovascular fitness, 24 h blood pressure monitoring and Doppler echocardiography parameters were obtained in 50 untreated children (37 males; mean age 12.2 + 2.5) with biopsy-proven NAFLD. Abnormalities in both cardiac function and geometry could be identified in the whole study population: prevalence of about 35% in left ventricular hypertrophy, 14% of concentric remodelling and 16% of left atrial dilatation. Furthermore children with NAFLD (NAS score <5) showed lower cardiac alterations compared to NASH patients (NAS score >5). After adjusting for age, sex and BMI, a positive correlation was found only between LV mass and NAS score (p < 0.001). CONCLUSION: Our results suggest that cardiac dysfunction can be detectable early in NAFLD children and this is not linked to cardiovascular and metabolic alteration, other than to liver damage. Although as a preliminary stage, we can speculate a possible direct relationship between liver and heart steatosis, already occurring during childhood.

Is retroperitoneoscopic renal ablative surgery easier and safer using a new hemostatic device compared with clips and monopolar coagulation? A comparative study.

AIM: The aim of study was to retrospectively analyze our series of total and partial retroperiotoneoscopic nephrectomies performed in the last 5 years. METHODS: Twenty-two procedures were performed, 20 patients underwent nephrectomy and 2 patients underwent partial nephrectomy. The 20 patients who underwent nephrectomy were divided in 2 groups: group 1 (G1) patients-1-10, for whom we performed the procedure using monopolar coagulation, and group 2 (G2) patients 11-20 for whom we used a new hemostatic device to perform dissection and hemostasis. The results were analyzed using χ2 test. The results of partial nephrectomies were analyzed separately. RESULTS: No conversion were reported. We analyzed 6 parameters to compare the results: operative time (OT), estimated blood loss (EBL), need for transfusion (NT), complications, time to oral intake (TOI), hospital stay (HS). OT in G1 was in median 85 minutes, in G2 65 minutes (P=0.004); EBL was 15 mL for G1 and 5 mL for G2 (P=0.000.), NT was not necessary in both, in G1 we had 2 complications and 1 complication in G2; TOI was day 1 for both groups; median HS was 3 days for both. As for heminephrectomy, OT was 120 and 140 min, EBL 30 mL in both, NT not necessary, TOI was 1 day and HS 4 and 5 days respectively. CONCLUSION: Our study shows that the use of a new hemostatic devices reduce significantly OT and EBL in children underwent renal ablative surgery for benign pathologies compared with the use of monopolar coagulation.

Metal(loid)s and Rare Earth Elements in Posidonia oceanica (L.) Delile (1813) banquettes.

The Posidonia oceanica (L.) Delile 1813 banquette provides precious ecosystem services for Mediterranean beach nourishment and protection, representing an important way of energy transfer through marine-coastal habitats. It is surprising to note how it is poorly investigated, especially concerning its double role as potential sink and source of chemicals. In particular, few studies exist about the metal (loid)s occurrence and no data are available on emerging contaminants, such as Rare Earth Elements (REEs). The present research investigated for the first time the concentrations of twenty-eight metal(loid)s and fifteen REEs in a well-structured banquette along the Italian coast (Central Tyrrhenian Sea) showing that (i) metal(loid)s and REEs occur in banquettes, with higher relative concentrations of some metal(loid)s (B, Sr, Mn, Fe, Al, Zn) and REEs (Ce, Y, La, Nd) with no statistically significant seasonal variations; (ii) Posidonia banquettes may represent an interesting biological model for chemicals monitoring.

Bioarchaeology aids the cultural understanding of six characters in search of their agency (Tarquinia, ninth-seventh century BC, central Italy).

Etruria contained one of the great early urban civilisations in the Italian peninsula during the first millennium BC, much studied from a cultural, humanities-based, perspective, but relatively little with scientific data, and rarely in combination. We have addressed the unusual location of twenty inhumations found in the sacred heart of the Etruscan city of Tarquinia, focusing on six of these as illustrative, contrasting with the typical contemporary cremations found in cemeteries on the edge of the city. The cultural evidence suggests that the six skeletons were also distinctive in their ritualization and memorialisation. Focusing on the six, as a representative sample, the scientific evidence of osteoarchaeology, isotopic compositions, and ancient DNA has established that these appear to show mobility, diversity and violence through an integrated bioarchaeological approach. The combination of multiple lines of evidence makes major strides towards a deeper understanding of the role of these extraordinary individuals in the life of the early city of Etruria.

Paediatric and adolescent traumatic gastrointestinal injuries: results of a European multicentre analysis.

AIM: Paediatric gastrointestinal injuries (GIIs) are rare, and the aim of this multicentre study was to evaluate their outcomes in a large cohort. METHODS: Hospital databases of 10 European paediatric surgical centres were reviewed for paediatric traumatic GIIs managed between 2000-2010. RESULTS: Ninety-seven patients with a median age of 9 years (0-17 years) were identified, with 72 blunt and 25 penetrating GIIs. Initial diagnostics in 90 patients led to correct diagnosis in 71%. Diagnostics were delayed in 26 patients (median 24 h). Eighty-two patients required surgery (67 laparotomy, 12 laparoscopy and three other approaches). There was a 50% conversion in the laparoscopic group. Median hospital stay was 10 days (range 1-137 days), with longer duration influenced by associated injuries (n = 41). Diagnosis <24 h was associated with significantly shorter hospital stay compared to more than 24 h (p = 0.011). In one-third of patients, morbidities were not related to a diagnostic delay or type of injury. There were five lethal outcomes, four due to associated injuries. CONCLUSION: Initial diagnostics in traumatic paediatric GIIs provide false negatives in one-third of patients. Diagnostic delay <24 h is associated with a significantly shorter hospital stay. Although laparoscopy is associated with a conversion rate of 50%, it can be used for diagnosis in suspected cases to avoid nontherapeutic laparotomy.

Natriuretic peptide-guided therapy: further research required for still-unresolved issues.

It has been asserted that serial measurements of natriuretic peptides (NPs), i.e., B-type natriuretic peptide (BNP) or the amino-terminal fragment of pro-B-type natriuretic peptide (NT-pro BNP), could help modulate more accurately the intensity of drug treatment in patients with chronic heart failure (CHF). Nevertheless, there are still several open questions about the presumed role of NP-guided pharmacologic adjustment as a valuable strategy in this setting. In this review, we outline the main randomized controlled trials (RCTs) carried out to date regarding NP-guided therapy in CHF patients and we focus on some of the still-unresolved issues. In particular, we discuss which NP plasma level should be assumed as the optimal target level to be attained, and we debate the possible influence exerted by different age classes on clinical end points during NP-guided therapy. The possible advantages and limitations for the cardiovascular system arising from the functional activation of NPs in CHF patients are also discussed. Although the pooling of data derived from the RCTs demonstrates an overall effect of slightly significant improvement in clinical outcomes with the NP-guided approach, we have noted that there are some relatively large studies that failed to document a significant clinical improvement in terms of mortality and morbidity using an NP-guided strategy. Thus, in our opinion, larger and better conducted trials addressing the unresolved issues of NP-guided therapy should be undertaken in the future.

Cabergoline use and risk of fibrosis and insufficiency of cardiac valves. Meta-analysis of observational studies.

BACKGROUND: Therapy with ergot-derivative dopamine agonists (ergot-DAs) is suspected to cause or promote the development of insufficiency and regurgitation in previously normal cardiac valves. Thus, we conducted a systematic review and meta-analysis of the literature to determine whether administration of cabergoline, i.e., an ergot-DA used to treat Parkinson's disease (PD) or hyperprolactinemia, is associated with an increased risk of valve regurgitation compared with pharmacological regimens not comprising ergot-DAs or with no therapy. METHODS: Observational studies were selected from the Pubmed and Embase databases. Studies had to have assessed the prevalence, odds, or risk of cardiac valve regurgitation in patients who underwent chronic treatment with cabergoline for PD or hyperprolactinemia compared with patients with the same diseases whose therapy did not include cabergoline or another ergot-DA. Separate meta-analyses were performed for PD and hyperprolactinemia patients. RESULTS: On the basis of five studies, 634 PD patients were taking cabergoline, while 9,120 PD patients were treated with dopa/dopamine decarboxylase inhibitor, alone or associated with a non-ergot DA. Valvular regurgitation of any degree - at one cardiac valve or more - was more frequent in PD patients who were taking cabergoline compared to those treated with a non-ergot DA agent or not treated with any dopamine agonist [adjusted (inverse variance: iv) odds ratio: 7.25 95 % CI: 3.71-14.18; p < 0.0001]. On the other hand, pooled data from seven studies showed that patients with hyperprolactinemia who were taking cabergoline (n = 444) exhibited significantly higher odds of mild- to-moderate tricuspid regurgitation compared to untreated controls (n = 954) [adjusted (iv) odds ratio: 1.92 95 % CI:1.34-2.73; p = 0.0003]. No significant differences in mitral or aortic valve regurgitation were detected between hyperprolactinemic patients taking cabergoline and controls. CONCLUSION: In PD patients, the risk of valvular regurgitation of any grade involving one or more cardiac valves was proven to be strongly associated with cabergoline treatment. Furthermore, based on our results, hyperprolactinemic patients taking cabergoline have an increased risk of mild-to-moderate tricuspid valve regurgitation.

B-type natriuretic peptide. Guided vs. conventional care in outpatients with chronic heart failure: a retrospective study.

AIM: It is not known whether therapy assisted by determinations of serum B-type natriuretic peptide (BNP) may improve the outcome for outpatients with chronic heart failure (CHF). METHODS: A retrospective case-control study was carried out, enrolling patients with acutely decompensated heart failure (ADHF) who were followed up for a mean period of four months. The patients who had died or had new episodes of ADHF were studied as the cases. For each case, one living patient who was free from ADHF-related re-hospitalisations was recruited as control. Cases and controls were also matched for some variables to minimise possible confounding. The possible role of BNP-guided therapy as a predictor of decreased risk of deaths or new hospitalisations related to heart failure was explored. RESULTS: Twenty-eight cases and 44 controls were enrolled. A fall in BNP on the fifth day after admission was found to be a predictor of a decreased risk of the composite endpoint "death or new hospitalisation, heart failure-related" (hazard ratio=0.1508; 95% CI: 0.049 to 0.463; P=0.001). On the other hand, low glomerular filtration rate at admission (<60 mL/min/1.73 m2) was associated with increased risk of the abovementioned endpoint (hazard ratio=7.1785; 95% CI: 1.574 to 32.725; P=0.0113). On the contrary, BNP-guided therapy was associated with a similar risk of death and/or CHF-related hospitalisation, compared to the conventional clinical approach. CONCLUSION: A fall in BNP ≥60% from baseline on the fifth day after admission was found to be associated with a favorable clinical outcome in outpatients with CHF after four months of follow-up, irrespective whether this finding had been detected in patients treated according to the BNP-guided therapy or in patients treated with conventional clinical criteria. However, among the outpatients with previous ADHF, a substantial improvement in cardiovascular event rates could not be demonstrated in those treated with BNP-guided therapy compared with those undergoing usual, symptom-guided treatment.

[Laparoscopy-assisted jejunostomy in neurological patients with chronic malnutrition and GERD. Technical considerations and analysis of the results]. / La digiunostomia laparo-assistita nei pazienti neurologici con malnutrizione cronica e RGE. Considerazioni tecniche ed analisi dei risultati.

BACKGROUND: Feeding difficulties and gastroesophageal reflux (GER) are major problems in severely neurologically impaired children. Many patients are managed with a simple gastrostomy, with or without fundoplication. Unfortunately, fundoplication and gastrostomy are not devoid of complications, indicating the need for other options in the management of these patients. METHODS: Between January 2002 and June 2010, ten patients (age range, 18 months-14 years) have been treated by creating a jejunostomy with the laparoscopic-assisted procedure. The procedure was performed using 2-3 trocars. The technique consists of identifying the first jeujnal loop, grasping it 20-30 cm away from the Treitz ligament, and exteriorizing it to the trocar orifice under visual guide. The jejunostomy was created outside the abdominal cavity during open surgery. At the end of the jejunostomy, the correct position of the intestinal loops was evaluated via laparoscopy. RESULTS: Surgery lasted 40 min on average, the laparoscopic portion about 10 min. Hospital stay was 3 or 7 days for all patients. At the longest follow-up (8 years), all patients had experienced a significant weight gain. One patient died 1 year after the procedure of unknown causes. As for the other complications: 4/10 patients experienced peristomal heritema, 2/10 device's dislocation and 1 patient a peristomal granuloma. CONCLUSIONS: Laparoscopic-assisted jejunostomy is a safe and effective procedure to adopt in neurologically impaired children with feeding problems and GER. We advocate the use of this procedure in neurologically impaired patients with feeding problems and reflux due to its overall practicability and because there is minimal surgical trauma. The improvement in the quality of life of these children after the jejunostomy seems to be the major advantage of this procedure. However the management of jejunostomy can be difficult for parents above all in the first postoperative months.