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Approximately 50% of melanomas, 30–40% of lung and breast cancers and 10-20% of renal and gastrointestinal tumors metastasize to the adrenal gland. Metastatic adrenal involvement is diagnosed by CT with contrast medium, ultrasound (which does not explore the left adrenal gland well), MRI with contrast medium and 18 FDGPET-CT which also evaluates lesion uptake. The simulation CT should be performed with contrast medium; an oral bolus of contrast medium is useful, given adrenal gland proximity to the duodenum. The simulation CT may be merged with PET-CT images with 18 FDG in order to evaluate uptaking areas. In contouring, the radiologically visible and/or uptaking lesion provides the gross tumor volume (GTV). Appropriate techniques are needed to overcome target motion. Single fraction stereotactic radiotherapy (SRT) with median doses of 16–23 Gy is rarely used. More common are doses of 25–48 Gy in 3–10 fractions although 3 or 5 fractions are preferred. Local control at 1 and 2 years ranges from 44 to 100% and from 27 to 100%, respectively. The local control rate is as high as 90%, remaining stable during follow-up when BED 10Gy is equal to or greater than 100 Gy. SRT-related toxicity is mild, consisting mainly of gastrointestinal disorders, local pain and fatigue. Adrenal insufficiency is rare.

BACKGROUND: Thymomas can benefit of cytoreductive surgery even if a complete resection is not feasible. The pleural cavity is the most common site of progression and the resection of pleural metastases can be performed in selected patients. We evaluated the results of stereotactic body radiation therapy for the treatment of pleural metastases in patients not eligible for surgery. METHODS: We retrospectively selected 22 patients treated with stereotactic body radiation therapy for pleural metastases between 2013 and 2019. According to RECIST criteria 1.1 modified for thymic epithelial tumors, time to local failure and progression free survival were calculated using Kaplan-Meier method. RESULTS: The median age was 40 years (range, 29–73 years). There were 1 A, 3 AB, 3 B1, 3 B2, 3 B2/B3 and 9 B3 thymomas. Pleural metastases and primary tumor were synchronous in 8 patients. Five patients had a single pleural metastatic site and 17 presented multiple localizations. Sixteen patients received stereotactic body radiation therapy on multiple sites of pleural metastases. The median dose of radiation was 30 Gy (range, 24–40 Gy). With a median follow-up of 33.2 months (95% CI: 13.1–53.3 months), ten patients experienced disease progression with a median progression free survival was 20.4 months (95% CI: 10.7–30.0 months). The disease control rate was 79% and 41% after 1 and 2 years, respectively. Local disease control rate was 92% and 78% after 1 and 2 years, respectively. There were not significant differences in progression free survival between patients diagnosed with synchronous and metachronous metastases (P=0.477), across those treated or not with chemotherapy (P=0.189) and between those who received or not a previous surgical resection of the pleural metastases (P=0.871). There were not grade 3–4 toxicities related to the treatment. CONCLUSIONS: Stereotactic body radiation therapy of pleural metastases is feasible and offers a promising local control of diseases. The impact of this treatment on patients’ survival is hardly predictable because of the heterogeneous clinical behavior of thymomas.

Background and aim The BRCA 1 and BRCA 2 genes are associated with an inherited susceptibility to breast cancer with a cumulative risk of 60% in BRCA 1 mutation carriers and of 30% in BRCA 2 mutation carriers. Several lifestyle factors could play a role in determining an individual’s risk of breast cancer. Obesity, changes in body size or unhealthy lifestyle habits such as smoking, alcohol consumption and physical inactivity have been evaluated as possible determinants of breast cancer risk. The aim of this study was to explore the current understanding of the role of harmful lifestyle and obesity or weight change in the development of breast cancer in female carriers of BRCA 1/2 mutations. Methods Articles were identified from MEDLINE in October 2020 utilizing related keywords; they were then read and notes, study participants, measures, data analysis and results were used to write this review. Results Studies with very large case series have been carried out but only few of them have shown consistent results. Additional research would be beneficial to better determine the actual role and impact of such factors.

Introduction: Stereotactic ablative radiotherapy (SABR) has been shown to increase survival in oligometastatic disease, but local control of colorectal metastases remains poor. We aimed to identify potential predictive factors of SBRT response through a multicenter large retrospective database and to investigate the progression to the polymetastatic disease (PMD). Material and methods: The study involved 23 centers, and was approved by the Ethical Committee (Prot. Negrar 2019-ZT). 1033 lung metastases were reported. Clinical and biological parameters were evaluated as predictive for freedom from local progression-free survival (FLP). Secondary end-point was the time to the polymetastatic conversion (tPMC). Results: Two-year FLP was 75.4%. Two-year FLP for lesions treated with a BED < 00 Gy, 100–124 Gy, and ≥125 Gy was 76.1%, 70.6%, and 94% (p = 0.000). Two-year FLP for lesion measuring ≤10 mm, 10–20 mm, and >20 mm was 79.7%, 77.1%, and 66.6% (p = 0.027). At the multivariate analysis a BED ≥125 Gy significantly reduced the risk of local progression (HR 0.24, 95%CI 0.11–0.51; p = 0.000). Median tPMC was 26.8 months. Lesions treated with BED ≥125 Gy reported a significantly longer tPMC as compared to lower BED. The median tPMC for patients treated to 1, 2–3 or 4–5 simultaneous oligometastases was 28.5, 25.4, and 9.8 months (p = 0.035). Conclusion: The present is the largest series of lung colorectal metastases treated with SABR. The results support the use of SBRT in lung oligometastatic colorectal cancer patients as it might delay the transition to PMD or offer relatively long disease-free period in selected cases. Predictive factors were identified for treatment personalization.

Background: Although FD may affect up to 10% of the general population, the therapy for FD is not standard. Recently, ginger-based food supplements have been proposed in order to restore FD symptoms. Our aim was to assess the efficacy of a new nutraceutical formulation containing extract of gingerol and thymus as a possible natural treatment in managing the symptoms of functional dyspepsia (FD). Methods: We retrospectively analyzed the efficacy and safety profiles of a nutraceutical formulation containing Zingiber officinalis root extract and a standardized Thymus extract. It was administered as 1 ml/day twice a day for 90 days. Patients were assessed at baseline and after 1, 2 and 3 months of treatment, following a month of pharmacological washout by completing a questionnaire reporting the trend of the following symptoms: epigastric pain, epigastric heaviness, early satiety, belching, and regurgitation. Every symptom was assessed by a Visual Analogic Scale (VAS), ranging from 0= absence to 10= maximal severity. Results: We enrolled 272 patients (99 males and 173 females; median IQR age 49.5, 36-64 yrs). Obesity (BMI>30) was present in 28 (12.5%) patients; smokers were 83 (30.5%); and comorbidities were present in 107 (39.3%) patients. Improvement of symptom scores during treatment and one month after its suspension was extremely significant (p Conclusion: This large study found that nutraceutical formulation could be one of the tools for an empirical approach to treat patients with FD, especially when a non-conventional drug treatment is preferable for the patient and considered suitable by the physician.

Court-involved non-incarcerated (CINI) youth endorse higher rates of lifetime suicide ideation (SI) and attempts than youth in the community. Brief intervention programs to address SI and related psychiatric symptoms upon entry into the juvenile justice system are rare. The current study reports the results of a pilot trial on a brief, coping intervention for CINI youth. Fifteen CINI youth (and caregivers) were eligible for participation based on youth report of SI or endorsing symptoms on a mental health screening tool. Youth completed a Coping Plan intervention with a master's-level counselor and received a 1-week follow-up call. Follow-up assessments were conducted at 1 and 3-months post-intervention. Participants were also interviewed about intervention acceptability. About half of the sample screened into the study based on SI and half screened in based on psychiatric symptoms on the Anxious/Depressed and Angry/Irritable subscales of the MAYSI-2. A reduction in SI and psychiatric symptoms was observed at 3-months post-intervention. Youth and caregivers reported the brief coping intervention was useful. This study highlights that intervening with youth with SI and psychiatric symptoms upon entry into the juvenile justice system can be successfully conducted with a population who historically has difficulty accessing mental health resources.

PURPOSE/OBJECTIVE(S): stereotactic ablative radiotherapy (SABR) has been shown to increase survival rates in oligometastatic disease (OMD), but local control of colorectal metastases still remains poor. We aimed to identify potential predictive factors of SBRT response through a multicenter large retrospective database and to investigate how lung SBRT can impact on the progression to the polymetastatic disease (PMD). MATERIALS/METHODS: the study involved 22 centers, and was approved by the Ethical Committee (Prot. Negrar 2019-ZT). 1023 lung metastases treated with SBRT in 622 patients were reported. The median BED was 105 Gy10. Lesion diameter GTV, PTV volume, dose, fractionations, and site of primary tumor were evaluated as potential predictive marker for SBRT response for the primary end-point local progression-free survival (LPFS). EGFR, KRAS, NRAS, BRAF, and MSI were also evaluated. Secondary end-point was the time to the polymetastatic conversion (ttPMC). RESULTS: the median follow-up was 26 months (range 3-117 months). The median lesion diameter was 13 mm (range 4-58 mm). The 2- and 3-year LPFS were 75.6% and 71%, respectively. At the univariate analysis, BED ≥125Gy10 was associated with improved LPFS (2-year: 94.1% versus 72.6%; P = < 0.0001), single fraction SBRT correlated with better LPFS in the overall population (2-year: 80.6% versus 73.7%; P = 0.03), but no significant difference was observed when considering the population treated with BED > 100 Gy10. Lesion diameter ≤19 mm correlated with improved LPFS (2-year 80% versus 60%; P = < 0.0001). The median ttPMC was 26 months, and the 2-year ttPMC was 54.5%. The median PFS was 11.3 months. After SABR, 36% patients had polymetastatic relapse, 39.5% patients had an oligometastatic relapse, and 24.5% patients had no further relapse. CONCLUSION: the present is the largest series of lung colorectal metastases treated with SABR. The results support the use of SBRT in lung oligometastatic colorectal cancer patients as it might delay the transition to PMD or offer relatively long disease-free period in selected cases. Several biological and clinical predictive factors were identified to assure the highest local control, on the basis of which a decisional algorithm will be derived.

Drug adulterants containing contaminants have been known to cause lung disease by inhalation or intravenous intake. Talcosis due to intravenous talc injection has been widely described in the literature, whereas the hypothesis of granulomatosis due to asbestos related to adulterated cocaine injection has not yet been explored. Herein, a case of pulmonary granulomatosis due to asbestos fibres related to cocaine injection in a young woman is described. Inorganic material in the lung was first individuated by light microscopy and last was identified using the SEM-EDX method. This case is unique since the occupational and passive inhalation of asbestos was excluded with absolute certainty.

Background Environmental factors may influence the lifetime risk of cancer (penetrance) in women with a BRCA mutation. Materials and methods In 89 BRCA-mutant women, affected or unaffected by breast/ovarian cancer, we explored serum levels of adipokines and their relation with the polymorphism SNP276G>T as modulators of BRCA penetrance. Results Affected women had significantly lower adiponectin than healthy women. Affected women with rs1501299 TT had significantly lower adiponectin and higher leptin than GT and GG genotypes. GT genotype was significantly associated with the disease status [odds ratio (OR)=3.24, 95% confidence interval (95% CI)=1.03-10.17]. Women in the lower tertile of serum adiponectin had a RR of BRCA-associated cancer of 2.80, 95% CI=1.1-7.1 (p for trend=0.03) compared with women in the higher tertile. Conclusion In the SNP rs1501299 the T allele was significantly associated with lower serum levels of adiponectin in affected women, suggesting that the T allele might be related to cancer.

BackgroundThe vagus nerve (VN), also called the pneumogastric nerve, connects the brainstem to organs contained in the chest and abdomen. Physiologically, VN stimulation can rapidly affect cardiac activity and heart rate (HR). VN neuropathy can increase the risk of arrhythmias and sudden death. Therefore, a selective test of VN function may be very useful. Since peripheral neurodynamic tests (NDT) are reliable for the assessment of neuropathies in somatic nerves, we aimed to validate a novel NDT to assess VN activity, namely, the VN-NTD.MethodsIn this cross-sectional double-blind, sex-balanced study, 30 participants (15 females) completed a checklist of autonomic dysfunction symptoms. During the VN-NDT administration, HR and symptoms (i.e., mechanical allodynia) were monitored in parallel to a real-time ultrasonography imaging (USI) and motion capture analysis of the neck. The VN-NDT impact on HR and its accuracy for autonomic symptoms reported in the last 7 days were tested.ResultsThe VN-NDT induced a significant HR reduction of about 12 and 8 bpm in males and females [t(1, 119) = 2.425; p < 0.017; ηp2 = 0.047, 95% confidence interval (CI): 0.93–9.18], respectively. No adverse events were observed during VN-NDT. A substantial interexaminer agreement between the evaluators in symptoms induction by VN-NDT was detected [F(1, 119) = 0.540; p = 0.464; ηp2 = 0.005, low effect]. Notably, mechanical allodynia accuracy for gastrointestinal dysfunctions was excellent (p < 0.05; 95% CI: 0.52–0.73; p < 0.001; 95% CI: 0.81–0.96).ConclusionsThe novel VN-NDT is a valid and accurate test capable of detecting VN activation with high sensitivity. Data provided are suitable for both sexes as a hallmark of HR variation due to VN normal response. The proposed VN-NDT may be reliable as daily routine neurological examination tests for the evaluation of neuropathic signs related to neuroinflammation of the VN.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier NCT04192877.

Acute diverticulitis is one of the most common surgical causes of admission to Emergency Departments in Western Countries. Although most of the cases can be managed conservatively or electively, a number of them will require an emergency surgical treatment. Among these patients, an even smaller number of them will present with a full-blown catastrophic septic shock. These minorities of cases have accounted for a significant part of the overall mortality and morbidity of complicated acute diverticulitis itself. The implementation of Damage Control strategies has shown to be useful also in these septic catastrophes, where a profound derangement of physiology makes unsafe a classic approach. Damage Control, as we intend it, is not a surgical “technique.” A close collaboration between different specialties brought forth a strategy of treatment. The Surgeon, the Anesthetist, and the Intensivist are the three most involved specialists in the treatment of these cases. It is paramount for them to learn how to work side by side and in harmony, since the patients will benefit from each-one’s input in their care.

The long pentraxin PTX3 is generating great interest given the recent discovery of its involvement in bone metabolism. This study investigates the role of circulating PTX3 as a marker of bone-related phenotypes in patients with osteoporosis (OP) and osteoarthritis (OA).Serum PTX3 levels were determined using an enzyme-linked immunosorbent assay (ELISA) in a total of OP (n=32), OA (n=19) patients and healthy controls (CTR; n=25). ROC curve analysis was carried out to evaluate the potential of PTX3 for the diagnosis of bone-related phenotypes. In addition, the association between PTX3 serum levels and biochemical markers was estimated by Spearman correlation analysis.Serum analysis reveals a statistically significant increase of PTX3 levels in OP and OA patients, compared to CTR subjects (**** p 0.0001, **** p 0.0001). ROC curve of PTX3 levels exhibits an excellent sensitivity and specificity for OP and OA diseases (**** p 0.0001 and **** p 0.0001, respectively). Moreover, serum PTX3 levels are positively associated with ALP (r = - 0.5257, p = 0.0083) and PTH levels (r = 0.4704, p = 0.0203) in OP patients.These results confirm the pivotal role of PTX3 in bone metabolism and suggest its potential use as a predictor of OP and OA bone-related phenotypes.

Acute cholecystitis (AC), frequently responsible for presentation to the emergency department, requires expedient diagnosis and definitive treatment by a general surgeon. Ultrasonography, usually performed by radiology technicians and reported by radiologists, is the first-line imaging study for the assessment of AC. Targeted point-of-care ultrasound (POCUS), particularly in the hands of the treating surgeon, may represent an evolution in surgical decision-making and may expedite care, reducing morbidity and cost.This consensus guideline was written under the auspices of the European Society of Trauma and Emergency Surgery (ESTES) by the POCUS working group. A systematic literature search identified relevant papers on the diagnosis and treatment of AC. Literature was critically-appraised according to the GRADE evidence-based guideline development method. Following a consensus conference at the European Congress of TraumaEmergency Surgery (Valencia, Spain, May 2018), final recommendations were approved by the working group, using a modified e-Delphi process, and taking into account the level of evidence of the conclusion.We strongly recommend the use of ultrasound as the first-line imaging investigation for the diagnosis of AC; specifically, we recommend that POCUS may be adopted as the primary imaging adjunct to surgeon-performed assessment of the patient with suspected AC. In line with the Tokyo guidelines, we strongly recommend Murphy's sign, in conjunction with the presence of gallstones and/or wall thickening as diagnostic of AC in the correct clinical context. We conditionally recommend US as a preoperative predictor of difficulty of cholecystectomy. There is insufficient evidence to recommend contrast-enhanced ultrasound or Doppler ultrasonography in the diagnosis of AC. We conditionally recommend the use of ultrasound to guide percutaneous cholecystostomy placement by appropriately-trained practitioners.Surgeons have recently embraced POCUS to expedite diagnosis of AC and provide rapid decision-making and early treatment, streamlining the patient pathway and thereby reducing costs and morbidity.

Background The long pentraxin PTX3 is generating great interest given the recent discovery of its involvement in bone metabolism. This study investigates the role of circulating PTX3 as a marker of bone-related phenotypes in patients with osteoporosis (OP) and osteoarthritis (OA). Methods Serum PTX3 levels were determined using an enzyme-linked immunosorbent assay (ELISA) in a total of OP (n=32), OA (n=19) patients and healthy controls (CTR; n=25). ROC curve analysis was carried out to evaluate the potential of PTX3 for the diagnosis of bone-related phenotypes. In addition, the association between PTX3 serum levels and biochemical markers was estimated by Spearman correlation analysis. Results Serum analysis reveals a statistically significant increase of PTX3 levels in OP and OA patients, compared to CTR subjects (**** p p p p r = − 0.5257, p = 0.0083) and PTH levels (r = 0.4704, p = 0.0203) in OP patients. Conclusions These results confirm the pivotal role of PTX3 in bone metabolism and suggest its potential use as a predictor of OP and OA bone-related phenotypes.

Background Myocardial bridge (MB) is the most common inborn coronary artery variant, in which a portion of myocardium overlies a major epicardial coronary artery segment. Myocardial bridge has been for long considered a benign condition, although it has been shown to cause effort-related ischaemia. Case summary We present the case of a 17-year-old female patient experiencing chest pain during physical activity. Since her symptoms became unbearable, electrocardiogram and echocardiography were performed together with a coronary computed tomography scan, revealing an MB on proximal-mid left anterior descending artery. In order to unequivocally unmask the ischaemic burden lent by MB, the patient underwent coronary angiography and physiological invasive test: instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) were calculated, both at baseline and after dobutamine infusion (5 µg/kg/min). At baseline, iFR value was borderline (= 0.89), whereas after dobutamine infusion and increase in the heart rate, the patient suffered chest pain. This symptom was associated with a decrease in the iFR value up to 0.77. Consistently, when FFR was performed, a value of 0.92 was observed at baseline, while after inotrope infusion the FFR reached the haemodynamic significance (= 0.79). Therefore, a medical treatment with bisoprolol was started. Discussion Our clinical case shows the importance of a comprehensive non-invasive and invasive assessment of MB in young patients experiencing chest pain, with significant limitation in the daily life. The coronary functional indexes allow to detect the presence of MB-derived ischaemia, thus guiding the decision to undertake a medical/surgical therapy.

Background and Aims: The Diverticular Inflammation and Complication Assessment (DICA) endoscopic classification of diverticulosis and diverticular disease (DD) is currently available. It scores severity of the disease as DICA 1, DICA 2 and DICA 3. Our aim was to assess the agreement on this classification in an international endoscopists community setting. Methods: A total of 96 doctors (82.9% endoscopists) independently scored a set of DD endoscopic videos. The percentages of overall agreement on DICA score and a free-marginal multirater kappa (κ) coefficient were reported as statistical measures of interrater agreement. Results: Overall agreement in using DICA was 91.8% with a free-marginal kappa of 88% (95% CI 80-95). The overall agreement levels were: DICA 1, 85.2%; DICA 2, 96.5%; DICA 3, 99.5%. The free marginal κ was: DICA 1 = 0.753, DICA 2 = 0.958, DICA 3 = 0.919. The agreement about the main endoscopic items was 83.4% (k 67%) for diverticular extension, 62.6% (k 65%) for number of diverticula for each district, 86.8% (k 82%) for presence of inflammation, and 98.5 (k 98%) for presence of complications. Conclusions: The overall interrater agreement in this study ranges from good to very good. DICA score is a simple and reproducible endoscopic scoring system for diverticulosis and DD.

Rationale & Objective: Studies of humans and animals have suggested that endogenous ouabain (EO) and related genes are mediators of acute (AKI) and chronic kidney injury. We sought to examine the relationship among EO levels, genetic variants in lanosterol synthase (LSS; an enzyme that catalyzes synthesis of cholesterol, a precursor of EO), and both AKI and chronic kidney injury. Study Design: 2 prospective observational cohort studies and a cross-sectional study of kidney tissue. Setting & Participants: (1) A prospective cohort study of patients undergoing cardiovascular surgery, (2) measurement of EO concentration in kidney tissue removed because of an adjacent tumor, and (3) a prospective cohort study of patients with newly diagnosed essential hypertension. Exposure: Missense variant in LSS (A instead of C allele at rs2254524), which leads to a valine to leucine substitution at amino acid 642. Outcomes: Development of postoperative AKI in the cardiovascular surgery cohort, EO concentration in kidney tissue, and estimated glomerular filtration rate (eGFR) reductions in the essential hypertension cohort. Analytical Approach: Logistic regression for analysis of postoperative AKI, analysis of variance for EO concentration in kidney tissue, and generalized linear models for changes in eGFR over time. Results: AKI incidence following cardiovascular surgery was greater among those with the LSS rs2254524 AA genotype (30.7%) than in those with the CC genotype (17.4%; P = 0.001). LSS rs2254524 AA kidneys had higher EO concentrations than CC kidneys (2.14 ± 0.29 vs 1.25 ± 0.08 ng/g; P < 0.001). In the longitudinal study of patients with essential hypertension (median follow-up, 4 years; range, 1-15 years), eGFR decline was greater among the LSS rs2254524 AA genotype group (−4.39 ± 1.18 mL/min/1.73 m2 per year) than in the AC or CC genotype groups (−1.07 ± 0.55 and −2.00 ± 0.45 mL/min/1.73 m2 per year respectively; P = 0.03). Limitations: These associations do not necessarily represent causal relationships; LSS rs2254524 variants may have effects on other steroid hormones. Conclusions: These findings support the potential value of LSS rs2254524 genotype–based risk stratification to identify patients at high risk for AKI before cardiovascular surgery, as well as predict accelerated eGFR in the setting of hypertension. These findings also suggest that LSS may in part drive EO-mediated kidney damage. EO may represent a new potential therapeutic target for the prevention of AKI and slowing of kidney damage in the setting of hypertension.

Osteoporosis is a public health concern all over the world. As a chronic condition, it generally requires prolonged medical interventions to limit the risks of further bone loss, impaired skeletal integrity and the onset of fractures. This problem is further complicated by the fact that the abrupt cessation of some therapies may be associated with an increased risk of harm. It is in this context that the COVID-19 pandemic has caused an unprecedented disruption to the provision of healthcare worldwide, exceeding our worst expectations in terms of the number of lives lost and the rapidity at which consolidated economies and healthcare systems are being significantly damaged. In this review, we assessed the challenges and strategies used in the management of osteoporosis and fragility fracture care during the COVID-19 pandemic. We also examined the available evidence and provided clinical recommendations that will require reassessment as the worldwide response to COVID-19 evolves.

Paget disease is a complex disorder that can be identified in the breast (mammary Paget disease) or in other locations (extramammary Paget's disease) such as ano-genital skin (Paget disease of the vulva -PVD). This condition is associated with low mortality, but a late diagnosis and recurrence can negatively impact the prognosis. Therefore, the main objective of this study is to evaluate if the human epididymis protein 4 (HE4) and cancer antigen125 (CA125) can promote recognition of PVD in early stages and during the relapses. we have conducted a prospective, observational and laboratory-based study, that included 50 patients, whose 25 healthy women represented the control group and 25 PVD patients, which have been operated in our Oncology Institute, from May 2017 to September 2019. Both in the control group and in PVD patients, the CA-125 and HE4 were evaluated before surgery and after 6 months. Finally, a comparison of markers serum level, both between before/after surgery and with control group, and a ROC (Receiver Operating Characteristic) curve were performed. Dosing the markers in PVD patients, 3/25 (12%) showed a higher value of CA125 and 11/25 (44%) an increased HE4. In addition, after surgical treatment there were no statistically significant difference between levels of CA-125 (P = .3) and HE4 (P = .19). On the other hand, comparing HE4 in PVD patients with the control group, a statistically significant difference was found (P-value = .0036). Contrary, comparing CA-125 in PVD patients with the control group (P-value= .1969), no statistically significant difference was evidenced. Moreover, ROC (Receiver Operating Characteristic) curve showed low sensitivity and specificity for CA125 with area under curve (AUC) = 0.5608. Instead, the ROC curve of HE4 revealed a sensitivity and specificity of 76% and 88% respectively (AUC = 0.7408) using a cut-off at 90 pmol/L. Despite the limited cases, our data showed that CA125 is not a sensitive marker for PVD. On the other hand, in 44% of PVD we’ve seen an increase in HE4. So, this could be a starting point for further research that could confirm the possibility to use this marker in order to support PVD early identification.

Objective: Traumatic events, including abuse, neglect, and other dangerous/shocking experiences, are commonly observed in adolescents with T2D. Research has shown there is a link between trauma and poorer health outcomes, yet, the extent to which trauma increases risk for developing T2D is not well understood. Trauma may heighten T2D risk through LOC eating, which can arise to cope with negative emotions. Our aim was to evaluate the links of trauma and LOC eating with T2D risk in adolescent girls with obesity. Methods: Participants (n=65, mean±SD 15.2±1.6y) were girls at-risk for T2D based on BMI ≥85%ile, ≥1 family member with T2D, and elevated depression (Center for Epidemiologic Studies Depression [CES-D] score ≥21). Trauma history (presence vs. absence) was assessed with the Schedule for Affective Disorders and Schizophrenia for School-Aged Children, and LOC eating (presence vs. absence) with the Eating Disorder Examination. T2D risk was assessed as HbA1c and Matsuda Whole Body Insulin Sensitivity Index (WBISI), derived from a 7-sample 2-hr OGTT. ANCOVA tested differences in HbA1c and WBISI by trauma and LOC, controlling for age, BMIz, race/ethnicity, and depression. Results: Trauma history was endorsed in 40.6% and LOC eating in 36.4% of girls. Girls with and without a trauma history reported similar rates of LOC (36.4% vs. 37.5%, p=.93). Girls with trauma had higher HbA1c (5.7±0.06%) vs. those with no trauma (5.5±0.05%, p=0.04), with no difference in WBISI (p=0.32). Girls with LOC had worse WBISI vs. those with no LOC (3.0±0.53 vs. 4.8±0.40, p Conclusions: Trauma history and LOC eating were unrelated to each other, but each related to different aspects of elevated T2D risk. Attention to both factors may warrant consideration in intervening to lessen T2D risk in teens with obesity and elevated depression. Disclosure V. Jimenez: None. A.M. Hilkin: None. M.M. Verros: None. E.L. Clark: None. M. Casamassima: None. R.L. Miller: None. L. Pyle: None. M.M. Kelsey: Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Janssen Pharmaceuticals, Inc., Merck Sharp & Dohme Corp. L.B. Shomaker: None.

Background: The Vagus Nerve (VN) neuropathies and autonomic peripheral neuropathies (APN) are responsible for neurodegenerative diseases and immune response alterations. Peripheral nerves selective tension tests (NDT) are clinical tools validated for neuropathies detection in lower and upper limbs. However, a validated NDT to assess VN is lacking. Methods: An estimated sample of 30 healthy subjects completed a questionnaire on vagal symptoms. The VN-NDT was administered, if neurological assessment of the cervical tract was negative. Symptoms and heart rate (HR) were monitored. The test validity was assessed using a motion capture analysis system and a real-time ultrasonography imaging (USI; C6-VN distance) during the test administrations. Inter-examiner accordance was tested (Cohen's Kappa) between two blinded assessors (one expert and one novice). Two-way analysis of variance (ANOVA) were performed with factors experience and side tested (2x2). A checklist with symptoms and signs of autonomic dysfunction was administered to all participants and accuracy, sensitivity, specificity, positive and negative likelihood ratios of the VN-NDT in autonomic dysfunction symptoms detection was calculated (ClinicalTrials.gov number, NCT04192877). The aim of the research was to define normtive data in order to establish a hallmark of physiological spectrum for pathology detection. Findings: The test induced a significant reduction of the C6-VN distance and of the HR (about 10 beats per minutes [bpm]; p< 0.01; d= .2; 95% confidence interval [CI]: 0.03–.3; p

Purpose: To present a selected series of extensively occlusive thrombosis of arteriovenous graft treated with the Penumbra’s Indigo System. Materials and Methods: Ten patients with acute (within 72 h) extensively occlusive thrombosis of arteriovenous graft (mean extension = 30.1 (range = 15–45) cm) were treated at our institution with the Indigo System. Of the 10 cases, thrombosis was extended to venous outflow in 7 cases and to both arterial inflow and venous outflow in 3 cases. Results: Both anatomic and clinical success were achieved in 8 of the 10 procedures (80.0%). In the 2 cases of technical failure, the patients underwent surgical thrombectomy with the finding of arteriovenous graft exhaustion, which was then replaced. The 6-month primary patency, primary-assisted patency, and secondary patency rates were 37.5% (3/8), 50.0% (4/8), and 62.5% (5/8). We reported 2 complications (one minor and one major adverse event). Conclusion: Percutaneous mechanical thrombectomy aspiration with Indigo System is a relatively safe and effective procedure and can be used even in extensively thrombosed arteriovenous graft.

Increasing pressure pushes towards the objective competence assessment of clinical operators. Hand motion analysis (HMA) was introduced to measure surgical and clinical procedures; its recent application to FAST examinations leaves unsolved issues. This study aimed at determining optimal HMA parameters to discriminate between operators’ skill levels, and which FAST tasks are experience-dependent. Ten experienced (EG) and 13 beginner (BG) sonographers performed a FAST examination on one female and one male model. A motion capture system returned the duration, working volume, number of movements (absolute and time normalized), and hand path length (absolute and time normalized) of each view. BG took more time in completing specific views, with a higher working volume (p = 0.003) and longer hands path (p

Purpose: The aim of this study is to present our personal experience using covered nitinol stent-graft in the treatment of outflow tract stenosis of arteriovenous grafts (AVGs) for hemodialysis access. Materials and Methods: Between May 2015 and October 2017, we retrospectively evaluated 36 (24 males, 12 females; mean age: 65.6 years) patients with AVGs on hemodialysis who underwent percutaneous angioplasty followed by endovascular stent-graft deployment for the treatment of stenosis of the venous outflow of the AVG. Indication for treatment included early restenosis (50% extending for a length >5 cm), and recoil of the stenosis after PTA performed with a noncompliant high-pressure balloon. Of 36 patients, 27 (75%) required surgical thrombectomy prior to endovascular procedure. Technical success, clinical success, primary and secondary patency, and safety were evaluated. Results: Technical success was 100%, and clinical success was 94.4%. Primary patency was 94.4%, 72.2%, 63%, 45.9%, and 45.9% at 1, 3, 6, 12, and 18 months (average: 215 days, range: 9-653 days); secondary patency was 94.4% and 86.1% at 1 and 3 months; 80.4% at 6, 12, and 18 months; and 53.6% at 24 months (average: 276.8 days, range: 9-744 days). No deaths were registered. Conclusions: In selected cases, the use of stent-graft represents an effective and safe solution for the treatment of stenotic complications of the venous outflow of AVGs, even in the setting of access thrombosis.

Matrix metalloproteinases are a family of zinc endopeptidases with proteolytic activity against the extracellular matrix components. In particular, two members of this family named Gelatinase A and B, as amply documented in the literature, play a key role in the process of tumor growth/metastasis in breast and hepatocellular carcinoma. Their activity is regulated by Tissue Inhibitor of metalloproteinases-1 and -2, which are the physiological inhibitor of Gelatinases A and B respectively. The aim of this review is to determine the current understanding of the clinical and prognostic role of Metalloproteinases-2 and -9 and their inhibitors in the course of breast cancer and liver diseases. Forty-one articles were selected from PubMed by entering the following keywords: liver diseases, breast cancer, MMP-2, TIMP-2; all articles were read and notes were made regarding the number of enrolled patients, pathology, measures, results and these data were used to write this review. Over-expression of both gelatinases is associated with the relapse of disease, metastasis, shorter overall survival in breast cancer and hepatocellular carcinoma and invasion and progression to tumors in chronic liver diseases, and MMPs/TIMPs ratio could be useful in the follow-up of these patients.

BACKGROUND/AIM Colorectal Cancer is the fourth most frequent cause of cancer death worldwide and its incidence increases from 50 years of age. It is often associated with protein-caloric malnutrition and 20% of cancer deaths occur due to this event. The aim of this study was to assess the prevalence of malnutrition and inflammatory status in 78 patients undergoing surgery for colorectal carcinoma. PATIENTS AND METHODS Nutritional Status was assessed by Mini Nutritional Assessment (MNA). Serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured by ELISA, while albumin, C-reactive protein (CRP) and transferrin (TRF) were tested using an immunometric assay. RESULTS The mean MNA score in colorectal patients was 20.4±8.4, while 23/78 patients (29.4%) were well nourished, 36/78 (46.1%) were at risk of malnutrition and 19/78 (24.3%) were malnourished, reporting in the previous six months from the date of diagnosis a significant weight loss (>10 kg), muscle mass loss and severe reduction of food intake due to loss of appetite and altered taste perception. The serum means of IL-6, TNF-α and CRP, were significantly higher in colorectal patients compared to the control group (p

Laparoscopy is being increasingly applied to pediatric inguinal hernia repair. In younger children, however, open repair remains preferred due to concerns related to anesthesia and technical challenges. We sought to assess outcomes after laparoscopic and open inguinal hernia repair in children less than or equal to 3 years. A prospective, single-blind, parallel group randomized controlled trial was conducted at three clinical sites. Children ≤3 years of age with reducible unilateral or bilateral inguinal hernias were randomized to laparoscopic herniorrhaphy (LH) or open herniorrhaphy (OH). The primary outcome was the number of acetaminophen doses. Secondary outcomes included operative time, complications, and parent/caregiver satisfaction scores. Forty-one patients were randomized to unilateral OH (n = 10), unilateral LH (n = 17), bilateral OH (n = 5) and bilateral LH (n = 9). Acetaminophen doses, LOS, complications, and parent/caregiver scores did not differ among groups. Laparoscopic unilateral hernia repair demonstrated shorter operative time, a consistent finding for overall laparoscopic repair in univariate (p = 0.003) and multivariate (p = 0.010) analysis. No cases of testicular atrophy were documented at 2 (SD = 2.7) years. Children ≤3 years of age in our cohort safely underwent LH with similar pain scores, complications, and recurrence as OH. Parents and caregivers report high satisfaction with both techniques.

Unhealthy lifestyle, as sedentary, unbalanced diet, smoking, and body composition change are often observed in non-Hodgkin’s lymphoma (NHL) survivors, and could be determinant for the onset of cancer treatment-induced metabolic syndrome (CTIMetS), including abdominal obesity, sarcopenia, and insulin resistance. The aim of this study was to assess whether changes in body composition, unhealthy lifestyles and types of anti-cancer treatment could increase the risk of metabolic syndrome (MetSyn) and sarcopenia in long-term NHL survivors. We enrolled 60 consecutive NHL patients in continuous remission for at least 3 years. Nutritional status was assessed by anthropometry-plicometry, and a questionnaire concerning lifestyles and eating habits was administered. More than 60% of survivors exhibited weight gain and a change in body composition, with an increased risk of MetSyn. Univariate analysis showed a significantly higher risk of metabolic disorder in patients treated with steroids, and in patients with unhealthy lifestyles. These data suggest that a nutritional intervention, associated with adequate physical activity and a healthier lifestyle, should be indicated early during the follow-up of lymphoma patients, in order to decrease the risk of MetSyn’s onset and correlated diseases in the long term.

PURPOSE: Acute mesenteric ischaemia (AMI) accounts for about 1:1000 acute hospital admissions. Untreated, AMI will cause mesenteric infarction, intestinal necrosis, an overwhelming inflammatory response and death. Early intervention can halt and reverse this process leading to a full recovery, but the diagnosis of AMI is difficult and failure to recognize AMI before intestinal necrosis has developed is responsible for the high mortality of the disease. Early diagnosis and prompt treatment are the goals of modern therapy, but there are no randomized controlled trials to guide treatment and the published literature contains a high ratio of reviews to original data. Much of that data comes from case reports and often small, retrospective series with no clearly defined treatment criteria. METHODS: A study group of the European Society for Trauma and Emergency Surgery (ESTES) was formed in 2013 with the aim of developing guidelines for the management of AMI. A comprehensive literature search was performed using the Medical Subject Heading (MeSH) thesaurus keywords "mesenteric ischaemia", "bowel ischaemia" and "bowel infarction". The bibliographies of relevant articles were screened for additional publications. After an initial systematic review of the literature by the whole group, a steering group formulated questions using a modified Delphi process. The evidence was then reviewed to answer these questions, and recommendations formulated and agreed by the whole group. RESULTS: The resultant recommendations are presented in this paper. CONCLUSIONS: The aim of these guidelines is to provide recommendations for practice that will lead to improved outcomes for patients.

cGMP-dependent protein kinase type I is a major mediator of cGMP signaling in the cardiovascular system. Recent studies on cardiac-specific PRKG1 knockout mice demonstrated that cGMP-dependent protein kinase type I mediates the negative inotropic effect of cGMP in the myocardium. We therefore investigated the association between left ventricular (LV) function and common polymorphisms in the PRKG1 gene in a general population. In 609 randomly selected participants (51.2% women; mean age, 48.8 years; 36.6% hypertensive) who were free from overt cardiac disease, we performed echocardiography and genotyped intronic tag single-nucleotide polymorphisms (SNPs) rs1904694, rs7897633, and rs7905063 in PRKG1. On the basis of color Doppler myocardial motion data, we calculated end-systolic longitudinal and radial deformation (strain) of the LV inferolateral wall. In multivariable-adjusted analyses accounting for confounders and relatedness, systolic radial strain was significantly ( P ≤0.005) higher in homozygotes for rs1904694 (GG), rs7897633 (AA), and rs7905063 (TT) compared with heterozygotes or noncarriers. Haplotype analysis confirmed that LV radial strain was significantly higher in GAT homozygotes than in noncarriers (62.3% versus 56.0%; P =0.0005). Transmission of the PRKG1 GAT haplotype to informative offspring was associated with higher LV radial strain (effect size, 6.11%; P =0.017). For other LV phenotypes, none of the phenotype–genotype associations reached statistical significance. In conclusion, LV systolic radial function was associated with common polymorphisms in PRKG1 . If experimental studies and longitudinal follow-up of LV function confirm the causality of this association, interference with cGMP-dependent protein kinase type I function might be a target for pharmacological intervention.

Introduction Peptic ulcer perforation (PPU) is a common surgical emergency and the mortality rate ranges 10% to 40%, especially in elderly patients. Laparoscopic repair achieved encouraging results. Materials and methods We enrolled patients performing surgical repair for PPU from January 2007 to December 2015 in our surgical unit. The aim of this retrospective observational study was to compare the results of PPU laparoscopic repair with open technique. The following characteristics of patients were evaluated: age, sex and American Society of Anesthesiologists classification. The site and the diameter of perforation were recorded: gastric, pyloric, duodenal, and the location on the anterior or posterior wall. Results In total, 59 patients (39 males and 20 females) with a mean age of 58.85 years (±SD) were treated surgically. Laparoscopic repair was accomplished in 21 patients. The mean operative time for laparoscopic repair was 72 minutes (±SD), significantly shorter than open repair time (180 min ±SD). The results demonstrated that laparoscopic repair is associated with a shorter operative time, reduced postoperative pain (4.75 vs. 6.42) and analgesic requirements, a shorter hospital stay (7.5 vs. 13.1), and earlier return to normal daily activities. Discussion Laparoscopic surgery minimizes postoperative wound pain and encourages early mobilization and return to normal daily activities. The benefit of early discharge and return to work may outweigh the consumable cost incurred in the execution of laparoscopic procedures. Conclusions Complications in both procedures are similar but laparoscopic procedure shows economic advantages for reducing postoperative hospital stay, postoperative pain, and for a good integrity of abdominal wall.

Although several molecular markers have been proposed as prognostic of disease progression in Hepatocellular carcinoma (HCC), predictive markers of response to treatment are still unsatisfactory. Here, we propose a genetic polymorphism as a potential predictive factor of poor prognosis in HCC patients treated with transcatheter arterial chemoembolization (TACE). In particular, we show that the guanosine insertion/deletion polymorphism in the promoter region of SERPINE1 gene at the −675 bp position, named 4G/4G, predicts poor prognosis in a cohort of 75 patients with HCC undergoing TACE. By a combination of ELISA and SERPINE1 promoter study, we found that the presence of elevated plasma levels of plasminogen activator inhibitor-1 (PAI-1) in patients with 4G/4G genotype is significantly associated with reduced overall survival compared to patients with 5G/5G or 4G/5G genotype in HCC patients after TACE. Our analysis provided evidence that variation in SERPINE1 gene plays a role in defining the outcome in patients treated with TACE. In addition to a poor disease outcome, the 4G/4G variant represents an unfavorable predictive factor for response to chemotherapy as well.

Background Reducing healthcare costs while maintaining quality of care is one of the challenges of the current healthcare system. The purpose of this study was to compare the hospital charges accrued following laparoscopic (LA) and open (OA) appendectomies in the pediatric population. Methods We retrospectively reviewed all pediatric appendectomies (n = 264) performed from 2007 to 2013 at a single academic center. Subgroup analysis on charges and costs was performed on perforated and nonperforated LA and OA. Results A total of 195 (73.9%) appendectomies were performed laparoscopically. LA in both perforated and nonperforated groups was associated with higher surgical supply, operating room, and total hospital charges compared with OA. Surgical supply costs to the facility were higher by an average of $1,000 for both nonperforated and perforated appendicitis in the LA group. Length of stay and postoperative complications were comparable within all groups. Conclusions In this study, LA is associated with significantly higher surgical costs and charges than OA without improvement in outcomes. Investigation into cost reduction strategies of laparoscopy should be a component of future clinical appendicitis research.

Twenty-four weaned female Hypor piglets (10.9 ± 0.1 kg mean BW) were used to evaluate the antioxidant effect of a natural extract, titrated in verbascoside, on blood and liver oxidative status in relation to a high intake of n-6 PUFA, inducing oxidative stress. Piglets were assigned to 1 of 3 experimental groups; the first group was fed a diet with 9% sunflower oil (T1) and the second received the sunflower oil diet supplemented with 5 mg of verbascoside/kg feed from Verbenaceae extract (Lippia spp.; T2). The third group was fed a control diet (CTR), in which an isoenergetic replacement of oil by starch was done. Blood samples were collected at the beginning and the end of the trial (30 d). At the end of the trial, the animals were slaughtered and the liver specimens were collected. Oxidative stress markers, including total antiradical activity, superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) activities, were determined in blood samples. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transferase (GGT) plasma levels were also evaluated. Immunohistochemistry and western blot analyses were performed in liver to evaluate heat shock protein (Hsp) 70, Hsp90, and Kupffer and Ito cell activation. Liver activities of SOD, GPX, and CAT were also determined. Total antiradical activity in blood and red blood cells were affected (P < 0.01) by dietary treatments. The n-6 PUFA supplementation at a high dosage for 30 d induced oxidative stress, decreasing total antiradical activity in blood and red blood cells (CTR vs. T1 + T2; P < 0.01) and plasma CAT activity (CTR vs. T1 + T2; P = 0.088) and increasing ALT value (CTR vs. T1 + T2; P < 0.01). Also, in liver, the CAT and GPX activities tended to be lower in pigs fed n-6 PUFA diets than pigs fed a control diet (CTR vs. T1 + T2; = 0.090 and = 0.085, respectively). The liver samples presented a normal architecture and no Ito and Kupffer cell activations were observed. In liver, the SOD activity tended to be lower in the T1 group (P = 0.064) than in the CTR and T2 groups. Moreover, the level of Hsp70 was higher (P < 0.01) in the T1 group than the CTR and T2 groups. These data suggest that the dose of dietary verbascoside partially restores the antioxidant status of the liver without affecting the systemic responses to oxidative stress induced by a high-fat diet.

Minimally invasive repair of pectus excavatum (MIRPE) is a well-established procedure. However, morbidity rate varies widely among institutions, and the incidence of major complications remains unknown.The American College of Surgeons 2012 National Surgical Quality Improvement Program-Pediatric (NSQIP-P) participant user file was utilized to identify patients who underwent MIRPE at 50 participant institutions. Outcomes of interest were overall 30-day morbidity, hospital readmission, and reoperation.Chest wall repair designated MIRPE accounted for 0.6% (n = 264) of all surgical cases included in the NSQIP-P database in 2012. The median age at surgical repair was 15.2 years. Thoracoscopy was used in 83.7% of cases. No mediastinal injuries or perioperative blood transfusions were identified. The 30-day readmission rate was 3.8%. Three patients (1.1%) required re-operation due to the following complications: superficial site infection, bar displacement and pneumothorax. The overall morbidity was 3.8% with no incidences of mortality.This analysis of a large prospective multicenter dataset demonstrates that major complications following MIRPE are uncommon in contemporary practice. Wound infection is the most common complication and the main cause of hospital readmission. Targeted quality improvement initiative should be focused on perioperative strategy to further reduce wound occurrences and hospital readmission.

To evaluate trends and factors associated with interfacility differences in imaging modality selection in the diagnosis and management of children with suspected acute appendicitis. We conducted a retrospective review of diagnostic imaging selection and outcomes in patients

OBJECTIVE In the setting of normal sodium (Na) intake, many patients with hypertension have inappropriately elevated plasma aldosterone (Aldo) levels and may be at increased risk for tissue damage. Moreover, other adrenocortical steroids, including endogenous ouabain can stimulate tissue damage. As endogenous ouabain is often elevated in chronically Na-loaded states, is a vasoconstrictor, raises blood pressure (BP), and also promotes tissue fibrosis, we investigated the extent to which plasma Aldo and endogenous ouabain were coelevated among naive hypertensive patients (NHP). We also investigated the impact of an acute salt load on these steroids, BP, and renal function. METHODS NHP (590) were grouped in tertiles based on their baseline plasma Aldo (mean ± SEM first 7.59 ± 0.18, versus third 24.15 ± 0.31 ng/dl). Baseline plasma renin activity (2.4 ± 0.1 versus 1.2 ± 0.1 ng/ml per h, P

Hypertension is a prevalent disorder in the world representing one of the major risk factors for heart attack and stroke. These risks are increased in salt sensitive individuals. Hypertension and salt sensitivity are complex phenotypes whose pathophysiology remains poorly understood and, remarkably, salt sensitivity is still laborious to diagnose. Here we present a urinary proteomic study specifically designed to identify urinary proteins relevant for the pathogenesis of hypertension and salt sensitivity. Despite previous studies that underlined the association of UMOD gene variants with hypertension, this work provides novel evidence showing different uromodulin protein level in the urine of hypertensive patients compared to healthy individuals. Notably, we also show that patients with higher level of uromodulin are homozygous for UMOD risk variant and display a decreased level of salt excretion, highlighting the essential role of UMOD in the regulation of salt reabsorption in hypertension. Additionally, we found that urinary nephrin 1, a marker of glomerular slit diaphragm, may predict a salt sensitive phenotype and positively correlate with increased albuminuria associated with this type of hypertension., Highlights • We identified urinary proteins differently excreted in hypertensive patients. • Nephrin 1 might predict salt sensitive phenotype and glomerular complications. • Uromodulin impacts salt homeostasis in hypertension. • We provide new insights into the pathogenesis of hypertension and salt sensitivity.

For a number of pediatric and adult conditions, morbidity and mortality are increased when patients present to the hospital on a weekend compared to weekdays. The objective of this study was to compare pediatric surgical outcomes following weekend versus weekday procedures.Using the Nationwide Inpatient Sample and the Kids' Inpatient Database, we identified 439,457 pediatric (18 years old) admissions from 1988 to 2010 that required a selected index surgical procedure (abscess drainage, appendectomy, inguinal hernia repair, open fracture reduction with internal fixation, or placement/revision of ventricular shunt) on the same day of admission. Outcome metrics were compared using logistic regression models that adjusted for patient and hospital characteristics as well as procedure performed.Patient characteristics of those admitted on the weekend (n=112,064) and weekday (n=327,393) were similar, though patients admitted on the weekend were more likely to be coded as emergent (61% versus 53%). After multivariate adjustment and regression, patients undergoing a weekend procedure were more likely to die (OR 1.63, 95% CI 1.21-2.20), receive a blood transfusion despite similar rates of intraoperative hemorrhage (OR 1.15, 95% CI 1.01-1.26), and suffer from procedural complications (OR 1.40, 95% CI 1.14-1.74).Pediatric patients undergoing common urgent surgical procedures during a weekend admission have a higher adjusted risk of death, blood transfusion, and procedural complications. While the exact etiology of these findings is not clear, the timing of surgical procedures should be considered in the context of systems-based deficiencies that may be detrimental to pediatric surgical care.

Minimally invasive repair of pectus excavatum (MIRPE) has become the treatment of choice in many centers in the recent years due to the successful surgical outcomes. The aim of this study was to investigate the results of MIRPE at our institute. Two hundred and fifty cases who had had MIRPE between August 2005 and February 2012 were included in the study and they were evaluated retrospectively according to the demographics, form of the deformity, number of retrosternal bars, operation duration, perioperative and postoperative complications, length of hospital stay, reoperations, bar removal and patient satisfaction. Two hundred and three of the patients were male, 47 were female and the median age was 16.5 (range: 6-36). The deformity was symmetric in 180 and asymmetric in 70 cases. One pectus bar was used in 157 cases, two in 87, three in 6 cases for the correction of the deformity. The median operation duration was 60 minutes (range: 20-180) and the median duration of hospital stay was 5 days (range: 2-10). Thirteen patients were reoperated due to inefficient correction of the deformity. Bars of the 30 patients have been removed on planned date without any recurrence in all but one patient. According to the evaluation of the quality-of-life questionnaires 95% of the patients were satisfied with surgical outcome. Minimally invasive repair of pectus excavatum is a successful surgical technique and can be preferred for the short operating time, low morbidity and high levels of patient satisfaction.

Circulating levels of endogenous ouabain (EO), a vasopressor hormone of adrenocortical origin, are increased by sodium depletion. Furthermore, lanosterol synthase, an enzyme involved in cholesterol biosynthesis, has a missense polymorphism (rs2254524 V642L) that affects EO biosynthesis in adrenocortical cells. Here, we investigated the hypothesis that lanosterol synthase rs2254524 alleles in vivo impact the blood pressure (BP) and EO responses evoked by a low dietary Na intake (P =0.013) and diastolic BP (DBP: −5.1±0.98 versus −1.4±0.94 mm Hg; P P =0.028). In addition, BP rose in ≈25% of the patients in response to the low salt diet and this was associated with increased circulating EO. Lanosterol synthase gene polymorphisms influence both the salt sensitivity of BP and changes in circulating EO in response to a low salt diet. The response of BP and EO to the low salt diet is markedly heterogeneous. Approximately 25% of patients experienced adverse effects, that is, increased BP and EO when salt intake was reduced and may be at increased long-term risk. The augmented response of EO to the low salt diet further supports the view that adrenocortical function is abnormal in some essential hypertensives.

Cardiovascular diseases remain the main cause of mortality and morbidity worldwide; primary prevention is a priority for physicians. Biomarkers are useful tools able to identify high-risk individuals, guide treatments, and determine prognosis. Our aim is to investigate Endogenous Ouabain (EO), an adrenal stress hormone with hemodynamic effects, as a valuable biomarker of heart failure. In a population of 845 patients undergoing elective cardiac surgery, we have investigated the relationships between EO and echocardiography parameters/plasmatic biomarker of cardiac function. EO was found to be correlated negatively with left ventricular EF (p = 0.001), positively with Cardiac End-Diastolic Diameter (p = 0.047), and positively with plasmatic NT-proBNP level (p = 0.02). Moreover, a different plasmatic EO level (both preoperative and postoperative) was found according to NYHA class (p = 0.013). All these results have been replicated on an independent cohort of patients (147 subjects from US). Finally, a higher EO level in the immediate postoperative time was indicative of a more severe cardiological condition and it was associated with increased perioperative mortality risk (p = 0.023 for 30-day morality). Our data suggest that preoperative and postoperative plasmatic EO level identifies patients with a more severe cardiovascular presentation at baseline. These patients have a higher risk of morbidity and mortality after cardiac surgery. Cardiovascular diseases remain the main cause of mortality and morbidity worldwide; primary prevention is a priority for physicians. Biomarkers are useful tools able to identify high-risk individuals, guide treatments, and determine prognosis. Our aim is to investigate Endogenous Ouabain (EO), an adrenal stress hormone with hemodynamic effects, as a valuable biomarker of heart failure. In a population of 845 patients undergoing elective cardiac surgery, we have investigated the relationships between EO and echocardiography parameters/plasmatic biomarker of cardiac function. EO was found to be correlated negatively with left ventricular EF (p = 0.001), positively with Cardiac End-Diastolic Diameter (p = 0.047), and positively with plasmatic NT-proBNP level (p = 0.02). Moreover, a different plasmatic EO level (both preoperative and postoperative) was found according to NYHA class (p = 0.013). All these results have been replicated on an independent cohort of patients (147 subjects from US). Finally, a higher EO level in the immediate postoperative time was indicative of a more severe cardiological condition and it was associated with increased perioperative mortality risk (p = 0.023 for 30-day morality). Our data suggest that preoperative and postoperative plasmatic EO level identifies patients with a more severe cardiovascular presentation at baseline. These patients have a higher risk of morbidity and mortality after cardiac surgery.

Cytokines play a crucial role in the host's immune response. In melanoma patients, cytokine profiles seems to be related to the clinical course and their imbalance could be associated to tumour progression. Thus, we studied a panel of baseline cytokines and their behaviour during treatment in order to verify their correlation with clinical outcomes. Interleukin-6, interleukin-8, interleukin-10, interleukin-12 and soluble receptor of interleukin-2 were evaluated in 90 out of 176 metastatic melanoma patients enrolled in a phase III study comparing chemotherapy and biochemotherapy. We divided patients into three different groups according to their own cytokine levels (low, intermediate and high) and then we correlated these groups with some clinical features. We also monitored the cytokines during the treatment in a subgroup of 37 patients. In univariate analysis, higher values of interleukin-6 (P = 0.005), soluble receptor of interleukin-2 (P = 0.001) and interleukin-12 (P = 0.010) were correlated with a worse survival. Conversely, interleukin-8 was unable to discriminate patients with different prognoses, and interleukin-10 was undetectable in the majority of patients. In multivariate analysis, only soluble receptor of interleukin-2 maintained its independent role in survival. The impact of baseline cytokines on response was insignificant. Regarding the behaviours of cytokines during treatment, the most remarkable aspect was a progressive increase of interleukin-12 and soluble receptor of interleukin-2 in patients with a better survival. In our metastatic melanoma patients, higher basal levels of interleukin-6, interleukin-12 and soluble receptor of interleukin-2 were associated with a worse survival. In contrast, a progressive increase of interleukin-12 and soluble receptor of interleukin-2 was observed during treatment in patients with a better survival.

Noonan syndrome is a genetic condition that can present with complex thoracic defects, the management of which often presents a surgical challenge. We present the surgical approach applied to a severe combined excavatum/carinatum deformity that had resulted in a Z-type configuration of the chest in a 9-year-old girl with Noonan syndrome.

The complexity and high cost of neonatal and pediatric intensive care has generated increasing interest in developing measures to quantify the severity of patient illness. While these indices may help improve health care quality and benchmark mortality across hospitals, comprehensive understanding of the purpose and the factors that influenced the performance of risk stratification indices is important so that they can be compared fairly and used most appropriately. In this review, we examined 19 indices of risk stratification used to predict mortality in critically ill children and critically analyzed their design, limitations, and purposes. Some pediatric and neonatal models appear well-suited for institutional benchmarking purposes, with relatively brief data acquisition times, limited potential for treatment-related bias, and reliance on diagnostic variables that permit adjustment for case mix. Other models are more suitable for use in clinical trials, as they rely on physiologic variables collected over an extended period, to better capture the interaction between organ systems function and specific therapeutic interventions in acutely ill patients. Irrespective of their clinical or research applications, risk stratification indices must be periodically recalibrated to adjust for changes in clinical practice in order to remain valid outcome predictors in pediatric intensive care units. Longitudinal auditing, education, training, and guidelines development are also critical to ensure fidelity and reproducibility in data reporting. Conclusion: Risk stratification indices are valid tools to describe intensive care unit population and explain differences in mortality.