Skipped Aganglionic Lengthening Transposition (SALT) is highly effective to achieve enteral autonomy in selected patients with intestinal failure secondary to total intestinal aganglionosis.

BACKGROUND: Intestinal Failure, parenteral nutrition (PN) dependence, and subsequent liver disease are the most challenging and life-threatening complications of short bowel syndrome experienced by patients with total intestinal aganglionosis. Skipped Aganglionic Lengthening Transposition (SALT) showed to be a promising procedure to overcome such problems. We herein report the results of two patients who underwent SALT at the Umberto Bosio Center for Digestive Diseases. PATIENTS AND METHODS: Between November 2019 and July 2022, 2 patients with total intestinal aganglionosis underwent SALT as autologous intestinal lengthening procedure. Perioperative data and long-term outcomes are reported. Patient #1-A 18 month-old male (PN dependant) with 30 cm of ganglionated bowel at birth experienced a 35% increase of intestinal length after SALT (from 43 to 58 cm) thanks to three 5 cm interposed aganglionic loops. Postoperative course was uneventful and he was totally weaned by PN after 28 months postoperatively. He is without PN only receiving enteric feeding 53 months after the procedure. Patient #2-A 11 year-old female (PN dependant) with 100 cm of ganglionated jejunum underwent SALT at 11 years and experienced a 19% increase of bowel length thanks to four 5 to 7 cm interposed aganglionic loops. Postoperatively she required excision of two out of the four loops due to severe strictures and inadequate perfusion with a subsequent overall 10% increase of length after SALT. Of note, she improved significantly with a progressive reduction of PN that has been stopped after 18 months. CONCLUSION: Skipped aganglionic lengthening transposition (SALT) seems to be very effective in improving nutrients absorption in patients with total intestinal aganglionosis by increasing absorptive bowel surface and decelerating intestinal flow for a longer and more effective contact of enteric material with ileal mucosa. Provided these impressive results are confirmed in the very long-term, SALT could become a valid alternative for the treatment of patients with total intestinal aganglionosis carrying at birth at least 20 to 30 cm of ganglionated jejunum.

Delayed diagnosis in Hirschsprung disease.

INTRODUCTION: Diagnostic delay in Hirschsprung disease is uncommon. Different definitions have been proposed but that of a diagnosis achieved after 12 months of age seems to be the most reliable and resorted to. Some authors reported a worse outcome in case of delay. Our study aims at providing the most relevant features of a series of patients who received a delayed diagnosis of Hirschsprung disease. MATERIALS AND METHODS: All consecutive patients admitted to our Center with a delayed diagnosis of Hirschsprung diseases between January 2017 and July 2023 have been retrospectively enrolled. Demographic data, phenotype, genotype, surgical complications, and outcome were assessed and compared to those of literature. A number of variables were also compared to those of a series of patients admitted during the same study period without a delayed diagnosis. RESULTS: A total of 45 patients were included (16.4% out of a series of 346 patients with data regarding age at diagnosis). Male to female ratio was 3.1:1. Median age at diagnosis was 41 months with a wide variation (range between 17 months and 58 years). All patients but 2 suffered from classic rectosigmoid aganglionosis. Normal meconium passage (58%) was reported in a significantly higher number of patients compared to what observed in a series without diagnostic delay (p = 0.0140). All other variables (associated anomalies, preoperative enterocolitis, complications, and functional outcome) proved not to have statistically significant differences compared to a series of patients without a diagnostic delay. CONCLUSIONS: The results of our study underline that a significant percentage of patients are basically missed in the neonatal period mostly due to mild symptoms. Overall outcome does not differ from that of patients without diagnostic delay. Nonetheless, we underline the importance of a throughout investigation of all patients with meconium delay/failure and that of adopting a low threshold for performing rectal suction biopsies in constipated children to avoid misdiagnosis to serve the best for our patients.

A unicentric cross-sectional observational study on chronic intestinal inflammation in total colonic aganglionosis: beware of an underestimated condition.

BACKGROUND: Inflammatory Bowel Diseases (IBD) are known to occur in association with Hirschsprung disease (HSCR). Most of cases are represented by Crohn Disease (CD) occurring in patients with Total Colonic Aganglionosis (TCSA) with an estimated prevalence of around 2%. Based on these considerations and on a number of provisional data belonging to our Center for Digestive Diseases, we developed a unicentric cross-sectional observational study aimed at describing phenotype, genotype, pathology and metagenomics of all patients with TCSA and Crohn-like lesions. RESULTS: Out of a series of 62 eligible TCSA patients, 48 fulfilled inclusion criteria and were enrolled in the study. Ten patients did not complete the study due to non-compliance or withdrawal of consent and were subsequently dropped out. A total of 38 patients completed the study. All patients were tested for chronic intestinal inflammation by a combination of fecal calprotectine (FC) or occult fecal blood (OFB) and underwent fecal metagenomics. Nineteen (50%) tested positive for FC, OFB, or both and subsequently underwent retrograde ileoscopy. Fourteen patients (36.8%) presented Crohn-like lesions, occurring after a median of 11.5 years after surgery (range 8 months - 21.5 years). No statistically significant differences regarding demographic, phenotype and genotype were observed comparing patients with and without lesions, except for need for blood transfusion that was more frequent in those with lesions. Faecal microbiome of patients with lesions (not that of caregivers) was less biodiverse and characterized by a reduction of Bacteroidetes, and an overabundance of Proteobacteria. FC tested negative in 3/14 patients with lesions (21%). CONCLUSIONS: Our study demonstrated an impressive 10-folds higher incidence of chronic inflammation in TCSA. Up to 50% of patients may develop IBD-like lesions postoperatively. Nonetheless, we failed in identifying specific risk factors to be used to implement prevention strategies. Based on the results of our study, we suggest screening all TCSA patients with retrograde ileoscopy regardless of FC/OFB values. The frequency of endoscopic assessments and the role of FC/OFB screening in prompting endoscopy is yet to be determined.

Intracranial bleeding risk after minor traumatic brain injury in patients on antithrombotic drugs.

BACKGROUND: Intracranial haemorrhage (ICH) risk after minor traumatic brain injury (mTBI) in patients on antithrombotic treatment is unclear. We compared ICH rates in mTBI patients on single, double and no antithrombotic therapy. Antithrombotic drugs encompassed vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs) and antiplatelets. Secondary aim was to identify potential predictors of ICH. METHODS: We retrospectively analysed consecutive adults referred to our emergency department for mTBI. All clinical information was retrieved by patients' charts review. Patients were divided in 5 groups: 1) no antithrombotic users, 2) antiplatelet users, 3) vitamin K antagonist users, 4) direct oral anticoagulants users, and 5) double antithrombotic users. RESULTS: A total of 1846 patients were enrolled, mean age 71 years (IQR 46-83); 1222 (66.2%) were in group 1, 407 (22.0%) in group 2, 120 (6.5%) in group 3, 51 (2.7%) in group 4 and 46 (2.5%) in group 5. At entry, 1387 (75.1%) patients underwent brain CT, 787 (64.4%) in group 1, 387 (95.1%) in group 2, 119 (99.2%) in group 3 and 51 (100%) in group 4 and 43 (93.5%) in group 5. ICH was documented in 36 patients (4.6%; CI 95%: 3.2-6.3) in group 1, 22 (5.9%; CI 95%: 3.6-8.5) in group 2, 5 (4.2%; CI 95%: 1.4-9.5) in group 3, 2 (3.9%; CI 95%: 0.5-13.5) in group 4 and 3 (7.0%; CI 95%: 1.5-19.1) in group 5 (p-value for across groups comparison = 0.86). At multivariable analysis GCS < 15 (OR 7.95 CI 95%: 3.12-20.28), post-traumatic amnesia (OR 6.49; CI 95%:3.57-11.82), vomiting (OR 4.45 CI 95%:1.47-13.50), clinical signs of cranial fractures (OR 8.41 CI 95%: 2.12-33.33), scalp lesions (OR 2.31 CI 95%: 1.09-4.89), but none of antithrombotic drugs were independently associated with ICH. CONCLUSION: mTBI-related ICH rate was similar in patients with and without antithrombotic use. Potential predictors of ICH can be drawn from patients' clinical examination.

Appropriateness of perioperative antibiotic prophylaxis in two Italian hospitals: a pilot study.

BACKGROUND: Appropriate perioperative antibiotic prophylaxis has been shown to be an effective measure for preventing surgical site infections and to avoid complications including increased antimicrobial resistance. The objective of the present study was to evaluate the appropriateness of perioperative antibiotic prophylaxis in two Italian hospitals. STUDY DESIGN: In 2016 a survey was prospectively carried out at two hospitals (identified as A and B) and all patients who underwent a surgical operation were enrolled. METHODS: For each patient, perioperative antibiotic prophylaxis data were collected and appropriateness of perioperative antibiotic prophylaxis was assessed according to the national guidelines (SNLG-17, 2011). RESULTS: During the study period, 107 and 467 operations were included. Compliance to perioperative antibiotic prophylaxis according to indication was 72.3% (hospital A) and 77.9% (hospital B). Perioperative antibiotic prophylaxis was administered <60 min before the skin incision in 89.1% of surgical procedures in hospital A and in 78.4% in hospital B. In hospital A, the recommended molecule of antibiotic was correctly administered in 87.8% of surgeries (n= 36), while, in hospital B, the antibiotic was correctly administered only in 9.8% of surgeries. Antibiotic prophylaxis was not extended postoperatively or did not exceed 24 hours after the end of the surgery in 99% and 8.9% of the procedures in hospital A and B, respectively. CONCLUSION: Our study found an overall low compliance to perioperative antibiotic prophylaxis mainly regarding antibiotic choice and total duration of prophylaxis. The Italian Study Group of Hospital Hygiene - Italian Society of Hygiene, Preventive Medicine and Public Health, together with the National Association of Hospital Physician, promoted the implementation of the project "Choosing wisely - Hospital Hygiene", and, among the list of the 5 procedures with the highest evidence of inappropriateness, the timing and the duration of administration of perioperative antibiotic prophylaxis have been included and a multicenter study has been launched to evaluate the appropriateness of perioperative antibiotic prophylaxis components in all the participating Italian hospitals.

Pulmonary embolism severity index accurately predicts long-term mortality rate in patients hospitalized for acute pulmonary embolism.

BACKGROUND: The Pulmonary Embolism (PE) Severity Index (PESI) is a clinical prognostic rule that accurately classifies PE patients into five risk classes with increasing mortality. PESI score has been validated in studies with a relatively short-term follow-up and its accuracy in predicting long-term prognosis has never been established. METHODS: Consecutive patients admitted to the tertiary care hospital of Varese (Italy) with an objectively diagnosed PE between January 2005 and December 2009 were retrospectively included. Information on clinical presentation, diagnostic work-up, risk factors, treatment and mortality during a 1-year follow-up was collected. RESULTS: Five hundred and thirty-eight patients were enrolled in this study. The mean age was 70.6 years (± SD 15.2), 44.4% of patients were male, and 27.9% had known cancer. One-year follow-up was available for 96.1% of patients. The overall mortality rate was 23.2% at 3 months, 30.2% at 6 months and 37.1% at 12 months. The discriminatory power of the PESI score to predict long-term mortality, expressed as the area under the ROC curve, was 0.77 (95%CI, 0.72-0.81) at 3 months, 0.77 (95%CI, 0.73-0.81) at 6 months and 0.79 (95%CI, 0.75-0.82) at 12 months. The PESI score confirmed its accurate prediction in patients without cancer. Simplified PESI had a similar overall accuracy to the original PESI at 3 and 6 months, but this was significantly lower at 1 year. CONCLUSIONS: The results of this study suggest that PESI score may also be an accurate tool to define the 6-month and 1-year mortality rates in PE patients.

Left ventricular remodeling in patients with metabolic syndrome: influence of gender.

AIM: The study was aimed to evaluate the influence of gender on left ventricular (LV) remodeling in metabolic syndrome (MetS). METHODS AND RESULTS: We enrolled 200 subjects without diabetes or overt cardiovascular diseases, never treated with anti-hypertensive drugs or statins: 60 men and 40 women with MetS matched by age, gender and 24 h systolic and diastolic blood pressure (BP) with 60 men and 40 women without MetS. The patients underwent blood tests, 24 h our BP monitoring, LV echocardiographic examination. LV mass indexed by eight(2.7) was significantly greater in men and women with MetS than without MetS. Compared with women without MetS, women with MetS had significantly higher posterior wall thickness and relative wall thickness, greater prevalence of LV concentric remodeling/hypertrophy and lower indices of LV diastolic function, whereas all these parameters were not significantly different between men with and without MetS. MetS was an independent predictor of relative wall thickness and LV mass index in women, but not in men. CONCLUSION: The impact of MetS on LV remodeling is significantly influenced by gender: the effects of MetS are more pronounced in women, with development of LV concentric hypertrophy/remodeling and preclinical diastolic dysfunction.

Left ventricular remodelling in asymptomatic HIV infection on chronic HAART: comparison between hypertensive and normotensive subjects with and without HIV infection.

The high cardiovascular risk of HIV infected (HIV+) patients is still partly unexplained. We aimed to evaluate if HIV infection and highly active antiretroviral therapy (HAART) are linked per se to left ventricular (LV) remodelling, independently of blood pressure (BP) values. We enrolled 4 groups of patients matched by gender, age, body mass index and smoking habit: 30 HIV+ hypertensives, 30 HIV+ normotensives, 30 not-infected (HIV-) hypertensives and 30 HIV- normotensives. HIV+ patients were on chronic HAART. Hypertension was newly diagnosed (≤6 months) and never treated. Each patient underwent blood tests, 24-h BP monitoring and LV echocardiogram. The 4 groups had similar fasting glucose and cholesterol; triglycerides, HOMA index and prevalence of metabolic syndrome were higher in the HIV+ groups. Despite similar 24-h BP values, HIV+ hypertensives had greater LV mass and higher prevalence of preclinical diastolic dysfunction than HIV- hypertensives. Compared to HIV- normotensives, HIV+ normotensives had similar 24-h BP values, but greater LV mass and lower LV diastolic indices, similar to HIV- hypertensives, whose 24-h BP values were higher. Asymptomatic HIV infection and chronic HAART are associated with myocardial hypertrophy and preclinical diastolic dysfunction, independently of BP values.

Prevalence of arterial and venous thromboembolic events in diabetic patients with and without the metabolic syndrome: a cross sectional study.

BACKGROUND: Metabolic syndrome (MS) is associated with an increased risk of cardiovascular events. Recent studies have found a higher prevalence of the MS in patients with idiopathic venous thromboembolic events (VTE) compared to controls suggesting a role of the MS in the pathogenesis of VTE. The presence of MS was shown to further increase the risk of arterial cardiovascular diseases (CVD) in diabetic patients. Conversely, there are no studies that have compared the risk of VTE in diabetic patients with and without the MS. METHODS: A cross sectional study comparing the prevalence of arterial cardiovascular events and VTE in diabetic patients with and without the MS was conducted. RESULTS: Nine hundred and fifty three patients were included in the study; 85.7% of patients had MS. Patients with the MS had an increased prevalence of CVD as compared with those without (23.4% vs. 11.8%) and the MS was an independent predictor of CVD in diabetic patients (OR 3.16, 95%CI 1.78, 5.59) after multiple logistic regression analysis. The prevalence of VTE was higher in patients with the MS in comparison to patients without the MS, but this association was not statistically significant (3,43% vs 1.47%; OR 2.38, 95% CI 0.56, 10.10%). CONCLUSION: Our study confirms the role of MS as an adjunctive cardiovascular risk factor in patients with diabetes. There is insufficient evidence to evaluate the role of the as an adjunctive risk factor for VTE in these patients. Further studies are necessary to confirm or refute these preliminary findings.

Components of arterial systolic pressure and RR-interval oscillation spectra in a case of baroreflex failure, a human open-loop model of vascular control.

The baroreflex control of circulation is always operating and modulates blood pressure and heart rate oscillations. Thus, the study of cardiovascular variability in humans is performed in a closed-loop model and the physiology of post-sinoaortic denervation is completely unknown in humans. We dissected for the first time the different components of systolic arterial pressure (SAP) and RR-interval spectra in a patient with 'baroreflex failure' (due to mixed cranial nerve neuroma) who represents a human model to investigate the cardiovascular regulation in an open-loop condition. Interactions among cardiovascular variability signals and respiratory influences were described using the multivariate parametric ARXAR model with the following findings: (1) rhythms unrelated to respiration were detected only at frequencies lower than classical low frequency (LF; Slow-LF, around 0.02 Hz) both in SAP an RR spectra, (2) small high-frequency (HF) modulation is present and related with respiration at rest and in tilt (but for SAP only) and (3) the Slow-LF fluctuations detected both in SAP and RR oscillate independently as the multivariate model shows no relationships between SAP and RR, and these oscillations are not phase related. Thus, we showed that in a patient with impaired baroreflex arc integrity the Slow-LF rhythms for RR have a central origin that dictates fluctuations on RR at the same rhythm but unrelated to the oscillation of SAP (which may be related with both peripheral activity and central rhythms). The synchronization in LF band is a hallmark of integrity of baroreflex arc whose impairment unmasks lower frequency rhythms in SAP and RR whose fluctuations oscillate independently.

Changes in autonomic modulation to the heart and intracellular catecholamines. A longitudinal study in differentiated thyroid carcinoma during short-term hypothyroidism and thyroid hormone replacement.

BACKGROUND: The effects of thyroid deprivation on the autonomic modulation to the heart remain controversial. METHODS: In this study in patients followed for thyroid carcinoma, we investigated (1) heart rate variability parameters and the baroreflex gain and (2) intracellular catecholamine levels in circulating lymphocytes during short-term hypothyroidism (phase 1) and after reinstitution of TSH-suppressive thyroid hormone replacement (phase 2). RESULTS: The RR interval value (p < 0.01) and systolic blood pressure (p < 0.05) were higher in phase 1 than in phase 2. The low-frequency/high-frequency (LF/HF) ratio was significantly lower in the hypothyroid state (p < 0.05), with a higher HF component (p < 0.05). After adjusting for mean RR interval in the regression model, the difference between the power of RR interval oscillations calculated in the two states was greater for the LF band (p = 0.005) and it was borderline significant for the HF band (p = 0.052). The baroreflex gain alpha(LF) index was similar in the two phases. The stimulus-induced cellular production of norepinephrine and epinephrine in peripheral blood mononuclear cells was significantly higher in phase 2. CONCLUSION: The neurally-mediated influences on the sinus node and the study of intracellular catecholamine production suggest a reduced sympathoexcitation in hypothyroidism compared with the treatment phase. The early increase in blood pressure observed after thyroid hormone withdrawal is not due to impaired sensitivity of the baroreflex arc.

Megakaryocytic blast crisis as first presentation of chronic myeloid leukemia.

We describe an extremely rare case of megakaryocytic blast crisis as first presentation of chronic myeloid leukemia. The patient had a very high platelet count and developed an ischemic stroke with seizures. She was treated with hydroxyurea, platelet apheresis, ARA-C, and idarubicin in order to obtain a prompt reduction of thrombocytosis and then with imatinib 600 mg/die PO. The therapy induced a complete hematological remission with a resolution of neurological signs within 4 weeks.

Electron-attachment resonances of glycine zwitterions from quantum scattering calculations: modeling macrosolvation effects.

A computational study of the quantum dynamics for low-energy electrons scattered by the isolated zwitterionic species of the glycine molecule is carried out using a model interaction potential described in the main text. The macroscopic effects of water solvation on the target molecule in the electron scattering problem are described through a continuum polarizable model (CPCM) which modifies the target molecular structure. In such a way, realistic molecular orbitals depicting the glycine zwitterion in solution are used to model the electron-molecule interaction. The results of the calculations indicate the presence of five different transient negative ions (TNIs) formed at energies from the threshold and up to about 6 eV. Although no nuclear motion was explicitly considered in the ensuing decay processes, the analysis of the nodal structures and density distributions for the resonant excess electron wavefunctions over the molecular space suggests possible anionic fragmentations that produce (Gly-H)-, H-, -CO2-, and -NH3. The likely consequences of such releases into the medium are briefly discussed.

Population isolates in South Tyrol and their value for genetic dissection of complex diseases.

The study of genetic isolates is a promising approach for the study of complex genetic traits. The small and constant population size, lack of migration, and multiple relationships between individuals in the isolate population could reduce the genetic diversity, and lead to increased levels of linkage disequilibrium (LD). We studied the extent of LD on Xq13 in six population isolates from South Tyrol in the Eastern Italian Alps. We found different levels of LD in our study samples, probably reflecting their degrees of isolation and their demographic histories. The highest values were obtained in Val Gardena (ranking among the highest levels of LD in Europe) and in Stelvio, which qualified as a microisolate according to historical information, and biodemographic and genealogical criteria. Phylogenetic analysis revealed that the two Ladin-speaking populations are genetically distant from each other, and from their German-speaking neighbours, and are characterized by a smaller effective population size than the neighbouring valleys. These peculiar characteristics suggest that South Tyrol could be a unique resource for the study of complex diseases, showing all the characteristics of isolated populations with the advantage of including, in a fairly homogeneous environment, two genetically differentiated sub-populations. This could allow investigators to gain an insight into the contribution of genetic heterogeneity in complex diseases.

H- desorption from uracil via metastable electron capture.

In this Letter we report an analysis of the quantum dynamics for the scattering of slow electrons off uracil molecules, leading to the formation of a trapped, metastable anionic state at around 9 eV of energy. This resonant state is seen to be capable of describing an anionic molecular precursor which can explain the desorption of the H- species observed in experiments on film deposited uracil samples.

Low-energy electron scattering by cubane: resonant states and Ramsauer-Townsend features from quantum calculations in the gas phase.

Calculations are carried out, using a nonempirical modeling of the interaction potential and solving the quantum scattering coupled channel equations, for low energy electron scattering from cubane (C8H8) molecules in the gas phase. Total integral cross sections are obtained and partial contributions are analyzed for the most important irreducible representations that describe the continuum electron in the Oh molecular symmetry. Several trapping resonances are found and analyzed in terms of the molecular-type features of the resonant electron states associated with them. A Ramsauer-Townsend minimum is also found and its possible behavior related to features of the scattering length as k --> 0.

Natriuretic peptides as markers of preclinical cardiac disease in obesity.

BACKGROUND: Aim of the study was to evaluate the role of atrial (ANP) and brain natriuretic peptides (BNP) as markers of preclinical cardiac disease in obesity. METHODS: We selected 26 obese (BMI > 29 kg m(-2)) never-treated hypertensives (24-h BP > 140 and/or 90 mmHg), 26 obese normotensives (24-h BP < 130/80 mmHg) and 25 lean (BMI < or = 25 kg m(-2)) never-treated hypertensives. Each subject underwent measurements of ANP and BNP plasma levels, 24-h ambulatory blood pressure (BP) monitoring, digitized M-mode and Doppler echocardiography. RESULTS: Mean values of ANP and BNP were similar among the three groups. All the subjects had normal left ventricular (LV) systolic function. Within each group ANP levels were higher in patients with LV diastolic dysfunction than in patients with normal diastolic function, and BNP levels were higher in patients with LV hypertrophy and in patients with LV diastolic dysfunction. Within each group, ANP levels were inversely correlated with LV diastolic indices, whereas BNP levels were directly correlated with LV mass index and inversely correlated with LV diastolic indices. ANP and BNP levels were not correlated with other echocardiographic parameters, age, BMI or 24-h BP values. CONCLUSION: In normotensive and hypertensive obese subjects the relationships of ANP and BNP levels with LV morpho-functional characteristics follow the same trend as in lean hypertensives, with ANP mainly influenced by diastolic dysfunction and BNP influenced by both LV hypertrophy and LV diastolic dysfunction. Therefore ANP and BNP can be considered useful markers of preclinical cardiac disease in obesity.

Comparative results between two groups of track-and-field athletes with or without the use of Master Amino acid Pattern as protein substitute.

Comparative results of this study have shown that athletes, by taking the Master Amino acid Pattern (MAP) as a dietary protein substitute and performing physical activity, have had (1) increased body muscle mass, strength, and endurance; (2) decreased fat mass; (3) increased basal metabolism rate; (4) greater improvement in performance of the nonprevailing muscles compared to the prevailing ones; and (5) improved muscular and hematologic lactate clearance, which allows for better muscle performance and faster muscle recovery after physical activity. It was concluded that the use of MAP as a dietary protein substitute in conjunction with physical activity can provide a safe and unprecedented way to optimize the body's protein synthesis, thereby improving anthropometric characteristics and physical and physiologic performance.