Radiological predictors of shunt response in the diagnosis and treatment of idiopathic normal pressure hydrocephalus: a systematic review and meta-analysis.

BACKGROUND: Patients with the dementia subtype idiopathic normal pressure hydrocephalus (iNPH) may improve clinically following cerebrospinal fluid (CSF) diversion (shunt) surgery, though the predictors of shunt response remain debated. Currently, radiological features play an important role in the diagnosis of iNPH, but it is not well established which radiological markers most precisely predict shunt responsive iNPH. OBJECTIVE: To conduct a systematic review and meta-analysis to identify radiological predictors of shunt responsiveness, evaluate their diagnostic effectiveness, and recommend the most predictive radiological features. METHODS: Embase, MEDLINE, Scopus, PubMed, Google Scholar, and JSTOR were searched for original studies investigating radiological predictors of shunt response in iNPH patients. Included studies were assessed using the ROBINS-1 tool, and eligible studies were evaluated using a univariate meta-analysis. RESULTS: Overall, 301 full-text papers were screened, of which 28 studies were included, and 26 different radiological features were identified, 5 of these met the inclusion criteria for the meta-analysis: disproportionately enlarged subarachnoid space (DESH), callosal angle, periventricular white matter changes, cerebral blood flow (CBF), and computerized tomography cisternography. The meta-analysis showed that only callosal angle and periventricular white matter changes significantly differentiated iNPH shunt responders from non-responders, though both markers had a low diagnostic odds ratio (DOR) of 1.88 and 1.01 respectively. None of the other radiological markers differentiated shunt responsive from shunt non-responsive iNPH. CONCLUSION: Callosal angle and periventricular changes are the only diagnostically effective radiological predictors of shunt responsive iNPH patients. However, due to the DORs approximating 1, they are insufficient as sole predictors and are advised to be used only in combination with other diagnostic tests of shunt response. Future research must evaluate the combined use of multiple radiological predictors, as it may yield beneficial additive effects that may allow for more robust radiological shunt response prediction.

Extended Tromograph Surveys for a Full Experimental Characterisation of the San Giorgio Cathedral in Ragusa (Italy).

Geophysical surveys are widely used to reconstruct subsoil seismo-stratigraphic structures with a non-invasive approach. In this study the geophysical surveys were carried out with the aim to characterise the San Giorgio Cathedral in Ragusa (Italy) and the area on which it is built from a dynamic point of view. A 3D subsoil model was realised through the integration of two active (i.e., seismic tomography and multichannel analysis of surface waves) and one passive seismic technique (horizontal to vertical spatial ratio). The instrumentation used for the latter method consists of a tromograph (Tromino®), which is also employed for the characterisation of the building, focusing on the façade and the dome, by means of an ambient vibration test, processed through the standard spectral ratio and frequency domain decomposition methods. Integration of the 3D model, showing the distribution of areas with different physicomechanical characteristics, enables identifying anomalies that are likely attributable to the remains of the ancient Byzantine church of San Nicola. Four lower modes mainly involving the two investigated macroelements are identified. The experimental results outline the advantages of the use of the tromograph both for soil and structural characterisation, especially for massive masonry buildings located in areas with high seismic hazard.

Application of Lyon Consensus criteria for GORD diagnosis: evaluation of conventional and new impedance-pH parameters.

OBJECTIVE: To validate Lyon Consensus criteria for diagnosing gastro-oesophageal reflux disease (GORD) by reflux monitoring. DESIGN: Manual review of impedance-pH tracings from patients with proton pump inhibitor (PPI)-dependent heartburn, evaluated off PPI. Acid exposure time (AET) thresholds defined by the Lyon Consensus and impedance parameters were investigated, namely, total refluxes (TRs), postreflux swallow-induced peristaltic wave (PSPW) index and mean nocturnal baseline impedance (MNBI). RESULTS: The study included 488 patients, 178 (36%) with normal (<4%) AET, 89 (18%) with inconclusive (4%-6%) AET and 221 (45%) with abnormal (>6%) AET, alongside with 70 healthy controls. At receiver operating characteristic analysis, area under curve was 0.89, 0.95 and 0.89 for TRs, PSPW index and MNBI, respectively, and threshold values were 40, 50% and 2000 Ω; the 4% physiological AET threshold defined by the Lyon Consensus showed 100% specificity but 63% sensitivity. The thresholds defined for impedance parameters were validated against AET by means of ordered logistic regression, being in concordance with the 4% AET threshold (OR 2.5 for TRs, 18.9 for PSPW index and 5.7 for MNBI). TRs positivity and concordant PSPW index/MNBI positivity were found in 80%-90% of patients in the abnormal AET group, in 73%-74% of cases in the inconclusive AET group and in 28%-40% of cases in the group with normal AET. CONCLUSIONS: Our results show the overall validity of the Lyon Consensus approach to GORD diagnosis. Adding evaluation of impedance parameters, namely, TRs, PSPW index and MNBI to AET appraisal, substantially improves the diagnostic yield of reflux monitoring.

Is the use of fully covered metal stents effective in the treatment of difficult lithiasis of the common bile duct?

BACKGROUND: The management of difficult lithiasis of common bile duct (CBD) often requires a multimodal approach. Fully Covered Metal Stents (FCSEMS) could fragment the stones, dilate strictures of the CBD and progressively enlarge the papillary orifice. The aim of the study was to evaluate the efficacy of FCSEMS in the treatment of difficult lithiasis of CBD. METHODS: All consecutive cases of difficult lithiasis of CBD after an attempt of clearance with complete sphincterotomy were retrospectively considered from 2009 to 2019. Intrahepatic lithiasis cases were excluded. Multivariable analysis (stepwise logistic regression if p value < 0.1 at univariable analysis) was made to understand factors associated with efficacy of FCSEMS in difficult lithiasis of CBD. RESULTS: 163 cases of difficult lithiasis over 1516 cases of lithiasis of CBD (incidence of 11%) were considered. Among eligible patients, 96 (mean age 78 ± 11.9 years, 43% males) placed a FCSEMS during the first ERCP. Mean diameter of stone was 17.5 ± 5.5 mm. An attempt of dilation during the same procedure was made in 18% cases. After removal of the stent, 52 (54%) patients had complete clearance of CBD at cholangiography. The rest of patients (44), subsequently underwent multimodal treatment (final success of 95%). After logistic regression, variables positively associated with clearance of CBD were sex male (OR 3.5) and stent permanence ≥ 30 days (OR 3.2). Diameter of the stone ≥ 2 cm was associated with failure (OR 0.2). 7 post-ERCP pancreatitis, 6 post-sphincterotomy bleeding and 3 cholangitis occurred. CONCLUSIONS: FCSEMS are useful in the approach of difficult lithiasis of CBD with no significant adverse events associated.

Cerebrospinal fluid and venous biomarkers of shunt-responsive idiopathic normal pressure hydrocephalus: a systematic review and meta-analysis.

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a neurodegenerative disease and dementia subtype involving disturbed cerebrospinal fluid (CSF) homeostasis. Patients with iNPH may improve clinically following CSF diversion through shunt surgery, but it remains a challenge to predict which patients respond to shunting. It has been proposed that CSF and blood biomarkers may be used to predict shunt response in iNPH. OBJECTIVE: To conduct a systematic review and meta-analysis to identify which CSF and venous biomarkers predict shunt-responsive iNPH most accurately. METHODS: Original studies that investigate the use of CSF and venous biomarkers to predict shunt response were searched using the following databases: Embase, MEDLINE, Scopus, PubMed, Google Scholar, and JSTOR. Included studies were assessed using the ROBINS-I tool, and eligible studies were evaluated utilising univariate meta-analyses. RESULTS: The study included 13 studies; seven addressed lumbar CSF levels of amyloid-ß 1-42, nine studies CSF levels of Total-Tau, six studies CSF levels of Phosphorylated-Tau, and seven studies miscellaneous biomarkers, proteomics, and genotyping. A meta-analysis of six eligible studies conducted for amyloid-ß 1-42, Total-Tau, and Phosphorylated-Tau demonstrated significantly increased lumbar CSF Phosphorylated-Tau (- 0.55 SMD, p = 0.04) and Total-Tau (- 0.50 SMD, p = 0.02) in shunt-non-responsive iNPH, though no differences were seen between shunt responders and non-responders for amyloid-ß 1-42 (- 0.26 SMD, p = 0.55) or the other included biomarkers. CONCLUSION: This meta-analysis found that lumbar CSF levels of Phosphorylated-Tau and Total-Tau are significantly increased in shunt non-responsive iNPH compared to shunt-responsive iNPH. The other biomarkers, including amyloid-ß 1-42, did not significantly differentiate shunt-responsive from shunt-non-responsive iNPH. More studies on the Tau proteins examining sensitivity and specificity at different cut-off levels are needed for a robust analysis of the diagnostic efficiency of the Tau proteins.

Cell stemness, epithelial-to-mesenchymal transition, and immunoevasion: Intertwined aspects in cancer metastasis.

Recent advances in tumor immunology, fostered by dramatic outcomes with cancer immunotherapy, have opened new scenarios in cancer metastasis. The cancer stemness/mesenchymal phenotype and an excess of immune suppressive signals are emerging as Intertwined aspects of human tumors. This review examines recent studies that explored the mechanistic links between cancer cell stemness and immunoevasion, and the evidence points to these key events in cancer metastasis as two sides of the same coin. This review also covers the mechanisms involved in tumor expression of programmed cell death ligand 1 (PD-L1), a major factor exploited by human neoplasias to suppress immune control. We highlight the convergence of mesenchymal traits and PD-L1 expression and examine the functions of this immune inhibitory molecule, which confers cancer cell resistance and aggressiveness.

Does fracture-extension into the pars interarticularis alter outcomes in odontoid failure? a technical note on pars interarticularis osteotomy and atlantoaxial distraction arthrodesis.

PURPOSE: Odontoid process fractures can extend rostral into the C2 arch. We investigated the clinical impact of a concurrent fracture of the pars interarticularis on odontoid failure. To overcome the surgical challenges related to the morphology of these fractures, we describe a novel surgical strategy using atlantoaxial joint distraction arthrodesis. METHODS: We conducted a single centre cohort study of 13 consecutive patients with odontoid fractures extending into the pars treated between June 2016 and June 2018. Criteria for a stable fibrous non-union were: Atlanto-Dens Interval (ADI) < 3 mm, Posterior Atlanto-Dens Interval (PADI) > 14 mm and lack of symptomatic motion at the fracture site. Atlantoaxial instability was defined as greater than 50% subluxation across the C1-C2 joint. Return to pre-injury performance status was considered a satisfactory clinical outcome. RESULTS: The mean age of the patient population was 77.2 years (SD 11.9). The mean follow-up time was 15 months (SD 5.2). 69% had an associated atlantoaxial instability (P-value 0.0005). Cervical orthosis treatment was associated with a high non-union rate (70%) (P-value 0.04) although it did not affect the overall clinical outcome. 2 cases presented with cord compression were treated surgically with pars interarticularis osteotomy and atlantoaxial distraction arthrodesis. CONCLUSIONS: Odontoid fracture with extension into the pars interarticularis often present with atlantoaxial instability and may result in stable fibrous non-union if treated non-operatively. The C1-C2 segment can be stabilised with atlantoaxial distraction arthrodesis achieved through an osteotomy of the pars interarticularis.

Clinical predictors of shunt response in the diagnosis and treatment of idiopathic normal pressure hydrocephalus: a systematic review and meta-analysis.

BACKGROUND: Positive shunt response (SR) remains the gold standard for diagnosing idiopathic normal pressure hydrocephalus (iNPH). However, multiple pathologies mimic iNPH symptoms, making it difficult to select patients who will respond to shunt surgery. Although presenting features, extended lumbar drainage (ELD), infusion test (IT), intracranial pressure monitoring (ICPM), and tap test (TT) have been used to predict SR, uncertainty remains over which diagnostic test to choose. OBJECTIVE: To conduct a systematic review and meta-analysis to identify clinical predictors of shunt responsiveness, evaluate their diagnostic effectiveness, and recommend the most effective diagnostic tests. METHODS: Embase, MEDLINE, Scopus, PubMed, Google Scholar, and JSTOR were searched for original studies investigating clinical predictors of SR in iNPH patients. Included studies were assessed using the QUADAS-2 tool, and eligible studies were evaluated using univariate and bivariate meta-analyses. RESULTS: Thirty-five studies were included. Nine studies discussed the diagnostic use of presenting clinical features, 8 studies ELD, 8 studies IT, 11 studies ICPM, and 6 studies TT. A meta-analysis of 21 eligible studies was conducted for TT, ELD, IT, and ICPM. ICPM yielded the highest diagnostic effectiveness, with diagnostic odds ratio (DOR) = 50.9 and area under curve (AUC) = 0.836. ELD yielded DOR = 27.70 and AUC = 0.753, IT had DOR = 5.70 and AUC = 0.729, and TT scored DOR = 3.86 and AUC = 0.711. CONCLUSION: Intraparenchymal ICPM is statistically the most effective diagnostic test, followed by ELD, IT, and lastly TT. Due to the higher accessibility of TT and IT, they are recommended to be used first line, using a timed-up-and-go improvement ≥ 5.6 s or a Rout cut-off range between 13 and 16 mmHg, respectively. Patients who test negative should ideally be followed up with ICPM, using mean ICP wave amplitude [Formula: see text] 4 mmHg, or 1- to 4-day ELD with an MMSE cut-off improvement [Formula: see text] 3. Future research must use standardized methodologies for each diagnostic test and uniform criteria for SR to allow better comparison.

SiLiF Neutron Counters to Monitor Nuclear Materials in the MICADO Project.

In the framework of the MICADO (Measurement and Instrumentation for Cleaning And Decommissioning Operations) European Union (EU) project, aimed at the full digitization of low- and intermediate-level radioactive waste management, a set of 32 solid state thermal neutron detectors named SiLiF has been built and characterized. MICADO encompasses a complete active and passive characterization of the radwaste drums with neutrons and gamma rays, followed by a longer-term monitoring phase. The SiLiF detectors are suitable for the monitoring of nuclear materials and can be used around radioactive waste drums possibly containing small quantities of actinides, as well as around spent fuel casks in interim storage or during transportation. Suitable polyethylene moderators can be exploited to better shape the detector response to the expected neutron spectrum, according to Monte Carlo simulations that were performed. These detectors were extensively tested with an AmBe neutron source, and the results show a quite uniform and reproducible behavior.

Is parathyroidectomy safe and effective in patients with normocalcemic primary hyperparathyroidism?

PURPOSE: Indications and advantages of parathyroidectomy in patients with normocalcemic primary hyperparathyroidism (NHPT) are still matter of debate. We aimed to compare clinical presentation and surgical outcome between normocalcemic and hypercalcemic forms in a consecutive series of patients who underwent parathyroidectomy for primary hyperparathyroidism. METHODS: Data of 731 consecutive patients were reviewed and retrospectively compared according to normocalcemic (group A) and hypercalcemic (group B) phenotypes. RESULTS: No significant differences were found between the two groups concerning demographics and symptomatic onset. Mean preoperative PTH levels were significantly higher in group B (252.0 ± 320.7 pg/ml vs 151.7 ± 112.0; p < 0.001). Mean PTH levels in first postoperative day were significantly lower in group B (30.9 ± 26.2 vs 22.7 ± 20.7; p < 0.001). No significant difference in overall accuracy of preoperative imaging studies was found. Significantly more patients in group A underwent bilateral explorations (83 vs 255; p < 0.05). The rate of multigland disease was significantly higher in group A (13.0 vs 6.8%; p < 0.05). At a mean follow-up period of 72.9 ± 46.8 months, all but three patients, among the 96 of group A who completed follow-up evaluation, were biochemically cured. The remaining patients had persistent high PTH values. Among NHPT patients who had target organ disease before parathyroidectomy, improvement in bone density and in kidney stones was observed in 41.7 and 40.0%, and stability in 50.0 and 60.0% respectively. CONCLUSION: In normocalcemic patients, parathyroidectomy is as safe and effective as in hypercalcemic patients. In the presence of symptoms and/or target organ disease, parathyroidectomy may have a positive effect on the outcome of NHPT patients.

A case of pulmonary edema: The critical role of lung-heart integrated ultrasound examination.

Cardiogenic pulmonary edema is a common presentation of acute heart failure normally treated with continuous positive airway pressure (CPAP), diuretics and nitrates. This therapy is contraindicated in case of cardiac tamponade. We describe a case of pulmonary edema due to cardiac tamponade in which integrated lung-heart ultrasound examination allowed prompt diagnosis and pericardiocentesis before administration of CPAP thus avoiding circulatory collapse.

Influence of carbon nanoparticles/epoxy matrix interaction on mechanical, electrical and transport properties of structural advanced materials.

The focus of this study is to design new nano-modified epoxy formulations using carbon nanofillers, such as carbon nanotubes, carbon nanofibers and graphene-based nanoparticles (CpEG), that reduce the moisture content and provide additional functional performance. The chemical structure of epoxy mixture, using a non-stoichiometric amount of hardener, exhibits unique properties in regard to the water sorption for which the equilibrium concentration of water (C eq) is reduced up to a maximum of 30%. This result, which is very relevant for several industrial applications (aeronautical, shipbuilding industries, wind turbine blades, etc), is due to a strong reduction of the polar groups and/or sites responsible to bond water molecules. All nanofillers are responsible of a second phase at lower glass transition temperature (Tg). Compared with other carbon nanofillers, functionalized graphene-based nanoparticles exhibit the best performance in the multifunctionality. The lowest moisture content, the high performance in the mechanical properties, the low electrical percolation threshold (EPT) have been all ascribed to particular arrangements of the functionalized graphene sheets embedded in the polymeric matrix. Exfoliation degree and edge carboxylated groups are responsible of self-assembled architectures which entrap part of the resin fraction hindering the interaction of water molecules with the polar sites of the resin, also favouring the EPT paths and the attractive/covalent interactions with the matrix.

Functional Heartburn Overlaps With Irritable Bowel Syndrome More Often than GERD.

OBJECTIVES: We aimed to evaluate the prevalence of irritable bowel syndrome (IBS) in patients with typical reflux symptoms as distinguished into gastroesophageal reflux disease (GERD), hypersensitive esophagus (HE), and functional heartburn (FH) by means of endoscopy and multichannel intraluminal impedance (MII)-pH monitoring. The secondary aim was to detect pathophysiological and clinical differences between different sub-groups of patients with heartburn. METHODS: Patients underwent a structured interview based on questionnaires for GERD, IBS, anxiety, and depression. Off-therapy upper-gastrointestinal (GI) endoscopy and 24 h MII-pH monitoring were performed in all cases. In patients with IBS, fecal calprotectin was measured and colonoscopy was scheduled for values >100 mg/kg to exclude organic disease. Multivariate logistic regression analysis was performed to identify independent risk factors for FH. RESULTS: Of the 697 consecutive heartburn patients who entered the study, 454 (65%) had reflux-related heartburn (GERD+HE), whereas 243 (35%) had FH. IBS was found in 147/454 (33%) GERD/HE but in 187/243 (77%) FH patients (P<0.001). At multivariate analysis, IBS and anxiety were independent risk factors for FH in comparison with reflux-related heartburn (GERD+HE). CONCLUSIONS: IBS overlaps more frequently with FH than with GERD and HE, suggesting common pathways and treatment. HE showed intermediate characteristic between GERD and FH.

Prognostic role of lactate on mortality in younger and older patients with cardio-respiratory failure admitted to an acute intensive care unit.

BACKGROUND AND AIM: Acidosis is able to induce negative changes of different organs that increase progressively with aging. At present it is not known whether the levels of lactate may differently influence the prognosis of younger and older patients. Thus, the aim of this study is to evaluate the prognostic value of lactate levels after admission of younger and older patients to an acute intensive care unit. METHODS: Younger (<65 years, n = 118) and older (≥65 years, n = 165) patients admitted to an acute intensive care unit were prospectively enrolled and classified according to diagnosis of acute heart or/and respiratory failure. For each patient, APACHE II score, time of hospitalization and mortality, blood levels of lactate were collected. RESULTS: Both in-hospital mortality and lactate >2.5 mmol/L at the admission was higher in the older than in the younger patients (42.4 vs. 20.3 %, p < 0.01 and 57.8 vs. 31.9 %, p < 0.01, respectively). Lactate level was higher in older than in the younger patients both at admission and after 24 h (3.9 ± 3.4 vs. 2.4 ± 2.2 mmol/L and 2.4 ± 2.0 vs. 1.4 ± 1.3 mmol, p < 0.01, respectively). Accordingly, multivariate analysis shows that lactate was predictive of mortality in younger (OR = 2.65, 95 % CI 1.62-5.24, p = 0.03) and even more in the older (OR = 4.74, 95 % CI 2.10-6.70, p < 0.01) patients. CONCLUSIONS: Lactate concentration increase is associated with increased mortality in younger patients but, even more so, in older patients admitted to an acute intensive care unit. These results confirm the experimental evidence showing acidosis has a greater effect of leading to organ failure and higher mortality with increasing age.

Association between baseline impedance values and response proton pump inhibitors in patients with heartburn.

BACKGROUND & AIMS: Esophageal impedance measurements have been proposed to indicate the status of the esophageal mucosa, and might be used to study the roles of the impaired mucosal integrity and increased acid sensitivity in patients with heartburn. We compared baseline impedance levels among patients with heartburn who did and did not respond to proton pump inhibitor (PPI) therapy, along with the pathophysiological characteristics of functional heartburn (FH). METHODS: In a case-control study, we collected data from January to December 2013 on patients with heartburn and normal findings from endoscopy who were not receiving PPI therapy and underwent impedance pH testing at hospitals in Italy. Patients with negative test results were placed on an 8-week course of PPI therapy (84 patients received esomeprazole and 36 patients received pantoprazole). Patients with more than 50% symptom improvement were classified as FH/PPI responders and patients with less than 50% symptom improvement were classified as FH/PPI nonresponders. Patients with hypersensitive esophagus and healthy volunteers served as controls. In all patients and controls, we measured acid exposure time, number of reflux events, baseline impedance, and swallow-induced peristaltic wave indices. RESULTS: FH/PPI responders had higher acid exposure times, numbers of reflux events, and acid refluxes compared with FH/PPI nonresponders (P < .05). Patients with hypersensitive esophagus had mean acid exposure times and numbers of reflux events similar to those of FH/PPI responders. Baseline impedance levels were lower in FH/PPI responders and patients with hypersensitive esophagus, compared with FH/PPI nonresponders and healthy volunteers (P < .001). Swallow-induced peristaltic wave indices were similar between FH/PPI responders and patients with hypersensitive esophagus. CONCLUSIONS: Patients with FH who respond to PPI therapy have impedance pH features similar to those of patients with hypersensitive esophagus. Baseline impedance measurements might allow for identification of patients who respond to PPIs but would be classified as having FH based on conventional impedance-pH measurements.