Nutrition in adult patients with selected lysosomal storage diseases.

Lysosomal storage disorders (LSDs) are a group of clinically heterogeneous disorders affecting the function of lysosomes and are characterized by an accumulation of undigested substrates within several cell types. In recent years there have been substantial advances in supportive care and drug treatment for some LSDs, leading to improved patient survival, as seen in Gaucher, Pompe and Fabry disease and some Mucopolysaccharidoses; however, many symptoms still persist. Thus it is now even more important to improve patients' quality of life and reduce symptoms and comorbidities. One potential way of achieving this goal is through adjunct nutritional therapy, which is challenging as patients may be overweight with associated consequences, or malnourished, or underweight. Furthermore, drugs used to treat LSDs can modify the metabolic status and needs of patients. There are currently not enough data to make specific dietary recommendations for individual LSDs; however, suggestions can be made for managing clinical manifestations of the diseases, as well as treatment-associated adverse events. The metabolic and nutritional status of adult patients must be regularly assessed and individualized dietary plans may be created to cater to a patient's specific needs. Damage to the autophagic process is a common feature in LSDs that is potentially sensitive to dietary manipulation and needs to be assessed in clinical studies.

Conservative treatment for interstitial monochorionic twin pregnancy: case report and review of the published work.

Interstitial pregnancy is considered one of the most hazardous types of ectopic pregnancies, with a mortality rate of 2-2.5%. We describe a case of a viable monochorionic twin pregnancy in a 35-year-old woman successfully treated with systemic methotrexate associated with bilateral uterine arteries' embolization. ß-hCG was undetectable 67 days after the first administration of methotrexate and the ultrasonography performed on day 67 showed the remnant of the gestational sac in the right uterine horn, a thin endometrium and a normal myometrial vascularization. Conservative treatment allowed us to avoid surgical treatment and to preserve the patient's fertility.

Atypical clinical and sonographic manifestations of lymphadenopathy in a child with cat-scratch disease: A case report.

Cat-scratch disease is a well-known infection in childhood. It usually presents as tender lymphadenopathy and should be included in the differential diagnosis of any lymphadenopathy syndrome. An history of exposure to cats supports the suspect and a positive serologic test to Bartonella henselae confirms the diagnosis. Ultrasound is the first line radiologic imaging performed in case of lymphadenopathy. The presence of hypoechoic lobular or oval mass with central hyperaemia and a possible adjacent fluid collection and surrounding oedema may differentiate the disease from other aetiologies. We describe the case of a 7-year-old girl presenting with an axillary lymphadenopathy, without a reported recent history of exposure to cats, with sonographic findings suggestive for cat-scratch disease. In this case, ultrasound was very useful in orienteering the diagnosis and insist on the medical history. Serology resulted positive for B. henselae and at the end the family remembered that 6 months before the child was scratched by a kitten.

Middle Cerebral Artery Dissection: A Report of Two Cases With Treatments and Outcomes.

In the present report, we describe two cases of right-sided M1 segment middle cerebral artery dissection in a 51-year-old Asian female and in a 28-year-old Caucasian male patient with no previous history of ischemic stroke or known intracranial atherosclerosis presenting with acute unilateral headache progressing to severe multifocal hemispheric infarction with nearly complete one-sided motor paralysis. In both patients, a middle cerebral artery dissection was detected on angiography; they were given exclusively medical therapy: patient 1 was not eligible to reperfusive therapies and was treated with a three-month course of acetylsalicylic acid and clopidogrel combined with low-dose enoxaparin, while patient 2 was initially treated with intravenous alteplase with no hemorrhagic complications and was later shifted to single antiplatelet therapy. Despite an initial worsening of clinical severity and an extensive ischemic lesion in both patients, neurologic function improved over time, eventually allowing recovery of unaided gait. Therefore, in the absence of signs of hemorrhage, intravenous thrombolysis or dual antiplatelet regimens could be considered in strokes related to middle cerebral artery dissection.

A simple active carbody roll scheme for hydraulically actuated railway vehicles using internal model control.

The paper presents the first classical internal model control (IMC) design in the context of railway carbody roll control. We propose a simple control approach for a recent hydraulically actuated vehicle body roll concept that offers limited carbody roll. The IMC approach addresses both preview- and nulling-type tilt setups, highlighting related benefits and limitations. The design provides a model simplification process that facilitates PI and PID-type control structures without the need for complex optimization. A simple, yet practical, tool for the industrial rail rolling stock engineer in vehicle control design is offered. Vehicle roll performance is rigorously studied on the deterministic (curving acceleration response) and stochastic (ride quality) trade off. Simulations are performed on an in-house multibody dynamics software package employing a realistic nonlinear railway vehicle model and allow to appropriately assess the performance of preview and nulling type tilt performance. The results obtained confirm that preview tilt control offers the better tilt performance as it utilizes a tilt command reference, and highlighted that nulling-type tilt performance remains at a relatively comparable level with the former.

Distribution in the brain and possible neuroprotective effects of intranasally delivered multi-walled carbon nanotubes.

Carbon nanotubes (CNTs) are currently under active investigation for their use in several biomedical applications, especially in neurological diseases and nervous system injury due to their electrochemical properties. Nowadays, no CNT-based therapeutic products for internal use appear to be close to the market, due to the still limited knowledge on their fate after delivery to living organisms and, in particular, on their toxicological profile. The purpose of the present work was to address the distribution in the brain parenchyma of two intranasally delivered MWCNTs (MWCNTs 1 and a-MWCNTs 2), different from each other, the first being non electroconductive while the second results in being electroconductive. After intranasal delivery, the presence of CNTs was investigated in several brain areas, discriminating the specific cell types involved in the CNT uptake. We also aimed to verify the neuroprotective potential of the two types of CNTs, delivering them in rats affected by early diabetic encephalopathy and analysing the modulation of nerve growth factor metabolism and the effects of CNTs on the neuronal and glial phenotypes. Our findings showed that both CNT types, when intranasally delivered, reached numerous brain areas and, in particular, the limbic area that plays a crucial role in the development and progression of major neurodegenerative diseases. Furthermore, we demonstrated that electroconductive MWCNTs were able to exert neuroprotective effects through the modulation of a key neurotrophic factor and probably the improvement of neurodegeneration-related gliosis.

Effect of Medication Reconciliation at Hospital Admission on 30-Day Returns to Hospital: A Randomized Clinical Trial.

Importance: According to international recommendations, hospitals should use medication reconciliation to prevent medication errors and improve patient safety. Objective: To assess the impact of medication reconciliation at hospital admission on patient-centered health care outcomes. Design, Setting, and Participants: This parallel group, open-label randomized controlled trial used centralized randomization to the intervention group (ie, individuals with medication reconciliation) or control group (ie, individuals with only standard, physician-acquired medication history). Outcome assessors and data analysts were blinded to group allocation. Participants included 1702 patients aged 85 years or older, with more than 10 medications at hospital admission, or meeting both conditions at 2 regional secondary teaching hospitals in southern Switzerland. Study duration was 14.5 months, from November 1, 2018, to January 15, 2020. Data were analyzed from December 2018 through March 2020. Interventions: Medication reconciliation was performed at hospital admission in 3 steps: (1) the pharmacy assistant obtained the list of the patient's current medications (ie, the best possible medication history [BPMH]); (2) the clinical pharmacist led reconciliation of the BPMH with the list of home medications recorded at hospital admission by the attending physician (according to the hospital standard procedure); and (3) medication discrepancies were communicated to the attending physician, and, when necessary, medications prescribed at admission were adapted. Main Outcomes and Measures: The primary outcome was a composite postdischarge health care use variable quantified as the proportion of patients with unplanned all-cause hospital visits (including visits to the emergency department and hospital readmissions) within 30 days after discharge from the hospital when medication reconciliation took place. A time-to-event analysis was performed. Results: Among 1702 patients (median [interquartile range] age, 86.0 [79.0-89.0] years; 720 [42.3%] men), 866 patients (50.9%) were allocated to the intervention group and 836 patients (49.1%) to the control group. The primary outcome occurred among 340 participants (39.3%) in the intervention group and 330 participants (39.5%) in the control group (P = .93). In time-to-event analyses at study closeout, unplanned all-cause hospital visits to the emergency department (log-rank P = .08) and unplanned all-cause hospital readmissions (log-rank P = .10) occurred similarly in the intervention and control groups. Conclusions and Relevance: These findings suggest that medication reconciliation at hospital admission has no impact on postdischarge health care outcomes among patients aged 85 years or older, with more than 10 medications at hospital admission, or meeting both conditions. Trial Registration: ClinicalTrials.gov Identifier: NCT03654963.

A mechatronic device for the rehabilitation of ankle motor function.

This paper presents the main results from a research aiming at the design of an electromechanical actuator for use in the rehabilitation of ankle motor function in patients suffering due to neurological diseases. Motivations for the research project are discussed within the framework of the application of mechatronic concepts for rehabilitation practice. The entire design process is then described, from the definition of project targets through the mechanical concept and control design steps until design validation by means of numerical simulations and tests on a prototype.

Detection of intracranial aneurysms with 64 channel multidetector row computed tomography: comparison with digital subtraction angiography.

PURPOSE: To compare the contribution of 64 channel multidetector row computed tomography angiography (64MDCT-angiography) with digital subtraction angiography (DSA) in the detection of intracranial aneurysms. METHODS AND MATERIALS: Twenty-nine patients (10 males and 19 females, age: 40-84 years; average: 61.9 years) with clinical and imaging findings strongly suggesting the presence of subaracnoid hemorrhage underwent 64MDCT-angiography and DSA with a short interval between the two examinations (less than 12 h-5 days). CT parameters were: 64 mm x 0.5 mm collimation, pitch-0.828 and helical pitch-53. DSA were performed with standard technique (four vessel catheterization) and multiple projections. Axial CT scans as well as maximum intensity projection, volume rendering and multiplanar reformations and angiographic views were independently reviewed by four readers (two for 64MDCT-angiography and two for DSA). Consensus was reached for discordant cases. DSA was considered as the standard of reference. RESULTS: In 29 patients, 28 aneurysms were found (14 patients had 1 aneurysm, 4 patients had 2 aneurysms and 2 patients had 3 aneurysms; in 9 patients no aneurysm were found). 64MDCT-angiography detected 26/28 aneurysms. No false-positive sites were recognized. The sensitivity, specificity, positive and negative predictive values and diagnostic accuracy were, respectively, 92.8, 100, 100, 99.4 and 99.5%. CONCLUSIONS: 64MDCT-angiography is helpful in detecting intracranial aneurysms with results similar to those of DSA but with less discomfort and risks for the patients and can be considered for the first line imaging technique. Conventional angiography is still needed in doubtful cases or negative MDCT-angiography associated with a strong clinical suspect.

The diagnostic journey of patients with mucopolysaccharidosis I: A real-world survey of patient and physician experiences.

UNLABELLED: Mucopolysaccharidosis type I (MPS I) is an inherited lysosomal storage disease. Affected individuals have disease ranging from attenuated to severe with significant disease burden, disability, and premature death. Early treatment with enzyme replacement therapy and/or stem cell transplantation can reduce disease progression and improve outcomes. However, diagnosis is often delayed, particularly for patients with attenuated phenotypes. We conducted a survey of 168 patients and 582 physicians to explore health care seeking patterns and familiarity of physicians with MPS I symptoms. Patients with attenuated MPS I typically first presented with stiff joints or hernia/bulging abdomen, and patients with severe disease with noisy/difficult breathing, or hernia/bulging abdomen. There was a mean delay from time of symptom presentation to diagnosis of 2.7 years for patients with attenuated disease, with a mean of 5 physicians consulted before receiving a correct diagnosis. MPS I was most commonly misidentified by physicians as rheumatoid arthritis (48-72%), with a wide variety of suspected diseases, including lupus. CONCLUSION: Patient and physician real-world surveys show that MPS I is under-recognized and diagnosis of MPS I remains delayed, particularly in patients with attenuated disease. Across regions and specialties, physicians require differential diagnosis education in order to improve early detection and early treatment initiation of MPS I.

White-matter alterations and callosal abnormalities in syndromic patients with mental retardation.

The aim of this study was to evaluate the frequency of callosal abnormalities and white matter alterations in syndromic patients. The authors report on the cerebral magnetic resonance imaging (MRI) morphologic analysis of the corpus callosum and white matter in 73 normal subjects and 61 syndromic patients. The study of the corpus callosum was carried out by MRI using different morphometric methods: measurement of the dimensions of length and thickness of genu, body, and splenium; measurement of angles obtained using the sagittal plane; and application of the proportional grid of Talairach. The evaluation of the white matter was carried out by applying a subjective grading scale. Abnormalities of the corpus callosum were found in about 50% of the syndromic subjects; in half of these cases, the abnormalities were associated with white matter alterations. In five syndromic patients (8.2%), the white matter alterations were not associated with corpus callosum abnormalities. This study shows that corpus callosum abnormalities are frequent in syndromology regardless of the syndrome type.

Enzyme-replacement therapy in a 5-month-old boy with attenuated presymptomatic MPS I: 5-year follow-up.

Mucopolysaccharidosis type I (MPS I) is a progressive and multisystemic disease, even in its attenuated Hurler-Scheie and Scheie forms. Clinical trials of enzyme-replacement therapy in MPS I have shown clinical benefit in patients with considerable preexisting disease, but no data exist on the effect of beginning enzyme replacement before the onset of significant clinical signs of disease. Here we present the 5-year follow-up of a boy with attenuated MPS I who had laronidase therapy initiated at the age of 5 months and compare his clinical course to that of his older sister, who began treatment at 5 years of age after she had developed typical signs of MPS I. After 5 years of treatment, the younger sibling has not developed any clinical manifestations of MPS I except for mild corneal clouding. In contrast, although many of the older sibling's clinical features have improved after 5 years of treatment, her dysostosis multiplex, cardiac valve involvement, and corneal clouding, although stabilized, have persisted. We suggest that early treatment of attenuated MPS I may significantly delay or prevent the onset of the major clinical signs, substantially modifying the natural history of the disease.

Comparison of contrast-enhanced ultrasonography versus baseline ultrasound and contrast-enhanced computed tomography in metastatic disease of the liver: diagnostic performance and confidence.

AIM: The aim of this study was to compare contrast-enhanced ultrasonography (CEUS) to baseline US and contrast-enhanced computed tomography (CT) in metastatic disease of the liver diagnosed or suspected by US during presurgical staging or postsurgical follow-up for primary malignancies. MATERIALS AND METHODS: Two hundred-fifty-three patients considered suitable for US due to the complete explorability of the liver and with one to five proven or suspected liver metastases at baseline US were included. All patients underwent US before and after microbubble injection, and multiphase contrast-enhanced CT. Independent panels of readers reviewed US and CT scans and recorded liver metastases according to a 5-grade scale of diagnostic confidence. Sensitivity, specificity (diagnostic performance) and area under the receiver operating characteristics (ROC) curve (diagnostic confidence) were calculated. RESULTS: Reference standards revealed no metastases in 57/253, more than five in 59/253, and one to five in 137/253 patients. In patients with one to five metastases, CEUS versus baseline US revealed more metastases in 64/137 and the same number in 73/137 patients while CEUS versus CT revealed more metastases in 10/137, the same number in 99/137, and lower number in 28/137. Sensitivity, specificity, and area under ROC curve of CEUS (83%, 84%, 0.929, respectively) differed from baseline US (40%, 63%, 0.579, respectively; P<0.01) while did not differ from CT (89%, 89%, 0.945, respectively; P>0.05). CONCLUSION: CEUS improved liver metastases diagnosis in comparison with baseline US while it revealed similar diagnostic performance and confidence to contrast-enhanced CT in patients considered suitable for US and with proven or suspected liver metastases at baseline US.

Detection of focal renal perfusion defects in rabbits after sulphur hexafluoride-filled microbubble injection at low transmission power ultrasound insonation.

The aim of this study was to assess the feasibility of contrast-enhanced ultrasound (US) at low transmission power insonation for diagnosis of focal renal perfusion defects (RPDs) in rabbits. In seven adult New Zealand White rabbits focal RPDs were induced by polyvinyl alcohol embolizing particles (150-250 microm in diameter) injected into the abdominal aorta. Three other rabbits that were not subjected to embolization were considered as controls. Both kidneys were insonated at baseline and after injection of sulphur hexafluoride-filled microbubbles at low transmission power (mechanical index 0.09-0.12). One sonologist assessed on-site RPD dimensions and conspicuity (visual score 0-4). Digital cine-clips were also reviewed off-site by two other independent readers, blinded, who assigned a confidence level (grades 1-5) for the RPD diagnosis. At on-site analysis RPDs appeared as focal areas of absent or diminished enhancement with a median visual conspicuity score=4. At off-site analysis RPDs >6 mm in diameter were identified at contrast-enhanced US, and the confidence in RPD diagnosis improved significantly (P<0.05) after microbubble injection (area under receiver operating characteristic curve 0.615 vs 0.972 by reader 1; 0.720 vs 0.953 by reader 2). Contrast-enhanced US at low transmission power insonation effectively identified RPDs with diameters >6 mm in rabbits.

An adult Sanfilippo type A patient with homozygous mutation R206P in the sulfamidase gene.

The Sanfilippo type A syndrome, one of the most frequent forms of mucopolysaccharidosis III, is characterized by severe mental retardation, progressive neurological degeneration, and mild somatic changes. It is due to a deficiency of heparan-N-sulfatase (sulfamidase) activity and consequent excretion of heparan sulfate in the urine. The disease is transmitted through an autosomal recessive mechanism, and more than 60 gene mutations have been identified. Up to now, only 10 cases of attenuated form of Sanfilippo type A syndrome have been described, and the specific mutation has been identified only in two of them. We report here on a female patient, 20 years old, with Sanfilippo type A syndrome presenting with a mild clinical phenotype characterized essentially by a moderate nonevolving mental retardation. The genetic analysis demonstrated that the patient is homozygous for mutation R206P; presence of polymorphism R456H was also found. This study places R206P as a mild mutation underlying Sanfilippo type A disease.

The first prebiotics in humans: human milk oligosaccharides.

The development of intestinal microflora in newborns is strictly related to the kind of feeding. Breast-fed infants, unlike the bottle-fed ones, have an intestinal ecosystem characterized by a strong prevalence of bifidobacteria and lactobacilli. Data available so far in the literature show that, among the numerous substances present in human milk, oligosaccharides have a clear prebiotic effect. They are quantitatively one of the main components of human milk and are only partially digested in the small intestine, so they reach the colon, where they stimulate selectively the development of bifidogenic flora. Such results have been recently proved both by characterization of oligosaccharides in breast-fed infant feces and by the study of intestinal microflora using new techniques of molecular analysis, confirming that human milk oligosaccharides represent the first prebiotics in humans.