Intracranial dural based marginal zone MALT-type B-cell lymphoma: a case - Based update and literature review.

OBJECTIVES: Dural based Marginal Zone MALT-type B-Cell Lymphoma (MZBCL) is an intracranial tumor that can mimicking meningioma both from a clinical and a radiological point of view. A standard treatment protocol is still lacking. Aim of the present work is to provide an update of the present literature regarding this rare neoplasia. PATIENTS AND METHODS: We report the case of a patient with a dural-based lesion mimicking a meningioma of the tentorium. After surgical treatment, the diagnosis was of MZBCL. A literature review is performed to highlight the typical characteristics of this rare intracranial lesion and to define the best therapeutic approach. RESULTS: Literature review included 38 articles describing 126 cases of intracranial dural-based MZBCL. No clinical trial has been found. Clinical and histopathological features are properly collected to provide a guide for future cases. Different treatment options have been attempted. Combination of surgery with adjuvant radiation therapy is the most used option. CONCLUSIONS: MZBCL should be considered in differential diagnosis for dural-based intracranial lesion. Surgery followed by radiation therapy is the most reported treatment. As a consequence of the rarity of this disease, of its indolent progression and of the lack of adequate follow-up, it is not possible to define it is the best treatment option.

Lumbo-sacral pedicular aplasia diagnosis and treatment: a systematic literature review and case report.

Aplasia of the lumbar pedicle is a rare condition, frequently associated with low back pain. Its recognition is fundamental in the definition of the correct treatment. We performed a literature review in order to clarify how to best diagnose and treat this rare anatomical condition. A comprehensive literature search for studies published through October 2020 was performed, using the following algorithm: "aplasia" OR "aplastic" OR "hypoplasia" OR "hypoplastic" OR "absent" OR absence" AND "pedicle" AND "lumbar" OR "sacral" OR "lumbosacral". References from reviewed papers were further evaluated for the inclusion of other relevant studies. Eighteen studies were included in the systematic review for a total of 24 adult patients. Another case of left L5 pedicle aplasia treated at our hospital has been described and included in the present review. This anatomical condition may be suspected in plain x-Ray, but CT scan 3D reconstructions may help to confirm the diagnosis in equivocal cases. Low-back pain and radiculopathy are the main signs and symptoms. The treatment was described in 14 cases. Eight patients underwent surgical intervention. In cases with spondylolisthesis, fusion surgery was performed with different techniques, obtaining an excellent clinical outcome. Pedicular aplasia is a rare condition that must be recognized in patients with a low back. When it is associated with spondylolisthesis, fusion surgery should be the preferred option.

Parietal interhemispheric transfalcine transtentorial approach for posterior incisural space lesions: from the lab to the operative room.

The operative approach to the posterior incisural space is challenging because of its deep location, the surrounding eloquent areas, and the intimate relationship with the deep veins. Several approaches have been proposed to manage the lesions in this region: supratentorial, infratentorial and a combination of them. Brain retraction, injury to the occipital lobe and corpus callosum, and venous bleeding are the principle drawbacks of these routes. We performed anatomical dissection study using 10 embalmed human cadaver specimens injected with colored latex exploring a different route, parietal interhemispheric transfalcine transtentorial (PITT). Then we used a PITT approach on two patients with posterior incisural space (PIS) lesions. The PITT approach led to successful and safe complete removal of PIS lesions in our cases. No complications were reported. The present approach could be a valuable option in case of PIS lesions, especially those associated with downward displacement of the deep venous complex; thanks to the gravity it reduce the complications related to the occipital lobe retraction and manipulation. Moreover, cutting the superior-anterior edge of the tentorium, the sub-tentorial space could be reached.

Modeling interaction between gp120 HIV protein and CCR5 receptor.

The study of the process of HIV entry into the host cell and the creation of biomimetic nanosystems that are able to selectively bind viral particles and proteins is a high priority research area for the development of novel diagnostic tools and treatment of HIV infection. Recently, we described multilayer nanoparticles (nanotraps) with heparin surface and cationic peptides comprising the N-terminal tail (Nt) and the second extracellular loop (ECL2) of CCR5 receptor, which could bind with high affinity some inflammatory chemokines, in particular, Rantes. Because of the similarity of the binding determinants in CCR5 structure, both for chemokines and gp120 HIV protein, here we expand this approach to the study of the interactions of these biomimetic nanosystems and their components with the peptide representing the V3 loop of the activated form of gp120. According to surface plasmon resonance results, a conformational rearrangement is involved in the process of V3 and CCR5 fragments binding. As in the case of Rantes, ECL2 peptide showed much higher affinity to V3 peptide than Nt (KD  = 3.72 × 10-8 and 1.10 × 10-6  M, respectively). Heparin-covered nanoparticles bearing CCR5 peptides effectively bound V3 as well. The presence of both heparin and the peptides in the structure of the nanotraps was shown to be crucial for the interaction with the V3 loop. Thus, short cationic peptides ECL2 and Nt proved to be excellent candidates for the design of CCR5 receptor mimetics.

Frequency of allergic sensitization to Can f 5 in North East Italy. An analysis of 1403 ISACs 112 (Component Resolved Diagnosis) collected retrospectively.

Summary: Recent studies have shown the increasing relevance of allergic sensitization to Can f 5, a prostatic kallicrein expressed in the prostate and detectable only in male dogs. The aim of the present study was to establish the frequency, level of sensitization and association with other dog allergens of Can f 5, as assessed by Component Resolved Diagnosis (CRD- ISAC 112, ThermoFisher Scientific, Uppsala, Sweden), in North East Italy. A total of 1403 CRD ISAC 112 were examined retrospectively. Five-hundred twenty subjects (37 %) had a positive IgE response to at least one of the available animal allergens. Among these 520 subjects, 268 (51.5 %) showed at least one sensitization to dog allergens. Among dog-sensitized individuals, 183 (69.02%) showed IgE against Can f 5, and 106 (57.92%) were sensitized exclusively against Can f 5. The average Can f 5 specific IgE was 8.810 ISU-E, with 77.6 % of individuals showing medium or high values of specific IgE according to manufacturer's specifications. In conclusions, our data confirmed that there is a high number of sensitized patients to Can f 5, which have a high degree of allergic sensitization. These results should be taken into account by allergists managing dog allergic patients. In fact, clinical consequences of this sensitization regard respiratory allergy (burden of rhinitis/asthma), systemic reactions (anaphylaxis during sexual intercourse from cross-reaction with human prostatic antigen), allergen immunotherapy-AIT (likely ineffective in patients with exclusive sensitization), and preventive measures (possibility to own a female dog and a likely reduction of allergen passive transport). Further studies are needed to better explore these aspects in "real life".

Anatomical variants of the basal vein of Rosenthal: prevalence in idiopathic subarachnoid hemorrhage.

BACKGROUND: Spontaneous, non traumatic subarachnoid hemorrhage (SAH) is a significant clinical problem that occurs most commonly as a result of aneurysm rupture. In approximately 15 % of cases, nor aneurysm or other vascular malformation can be identified by cerebral angiography as origin of the hemorrhage, and these are commonly defined as idiopathic SAH (ISAH). Because of the negative angiography, limited extension of the bleeding with prevalent prepontine pattern and the benign prognosis, the venous causes has been preferred rather than the arterial ones. In the literature recent studies have suggested a possible contribution by primitive variants of Basal vein of Rosenthal (BVR) in its the pathogenesis of ISAH, commonly grouped according Watanabe classification (type A, B and C). In this paper we evaluated the prevalence of anatomical variants of BVR in ISAH. METHODS: Venous drainage at angiography was retrospectively analyzed in 40 patients with ISAH and in 40 with unruptured aneurysms as controls. RESULTS AND CONCLUSIONS: Previous studies displayed a significant prevalence of BVR type C variants in ISAH. Conversely in our study we recognized variant B as prevalent, in which the BVR bifurcates to drain anteriorly into the uncal vein and posteriorly into the Galenic system. Similarly to variant C (in which the BVR drains via perimesencephalic "bridging" veins into cavernous, sphenoparietal, petrosal sinus or directly into transverse sinus) also variant B might be subjected to those stress mechanisms and intrinsic system 'fragility' and for reasons yet to determine, sets off a consequent hemorrhage with clinical and radiological features typical of ISAH.

IL-36 receptor antagonist with special emphasis on IL-38.

IL-36 is another family member of IL-1 and induces the production of proinflammatory cytokines and activates MAPK and NFkB pathways. IL-36 is a common mediator of innate and adaptive immune response and is inhibited by IL-36 receptor antagonist (RA). IL-36RA acts on IL-36 receptor ligand which exerts proinflammatory effect in vivo and in vitro. IL-38 binds to IL-36 receptor as does IL-36RA and has similar biological effects on immune cells. IL-38 is also a member of IL-1 cytokine and shares some characteristics of IL-1RA, binding the same IL-1 receptor type I. IL-38 plays a role in the pathogenesis of inflammatory diseases, exerting protective effect in some autoimmune diseases. Both IL-38 and IL-36RA have an anti-inflammatory biological effect, however in some cases have contrary effects.

Transcriptional profile characterization for the identification of peripheral blood biomarkers in patients with cerebral aneurysms.

We tried to identify molecular markers in peripheral blood to predict high risk of aneurysm rupture. Extraction of the total population of peripheral blood mononuclear cell (PBMC) from total blood volume, total RNA extraction from PBMC and Agilent One Color Gene-expression Oligo-Microarray were performed on peripheral venous blood samples from 45 patients with ruptured, unruptured cerebral aneurysms and control group (15). Mean foreground/ background signal intensities and A (log2(R*G)/2) values were calculated for each spot. Genes with absolute fold change (FC) greater than or equal to plus or minus 1.5 and p-value less than 0.05 were considered differentially expressed in the 3 groups (Student T-test). Genes coding for MMPs were strongly underexpressed in ruptured aneurysms group, suggesting a possible role in aneurysms development more than their rupture. Genes coding for adhesine proteins of the extracellular matrix (ICAM1) and cytoskeleton (WIPF1,TUBA4A) were underexpressed in ruptured aneurysms. Genes coding proteins involved in the regulation of apoptotic processes may be important in aneurysm development and rupture, resulting into an increased rate of remodeling processes in the arterial wall. Fas coding gene, SUMO1, ZFAT, BCL2, CCR5 genes were all over-represented in unruptured aneurysms. The coexisting over-representation of pro-apoptotic genes and the underexpression of cytoskeleton and extracellular matrix genes confirms that aneurysms development and evolution are part of a degenerative process of the arterial wall not involved in aneurysms rupture. MMPs may be involved in repairing chronic damages to the arterial walls and preventing SAH. Unexpectedly, Heat Shock Proteins (HSP90AA1, HSPA1A, HSPB1), G and RAS proteins, generally activated by stress situations were under-represented in aneurysmal walls. Further PCR and Western Blotting studies are needed to confirm such findings and to identify diagnostic and prognostic markers in order to define screening protocols for intracranial aneurysms.

Comparison of beneficial actions of non-steroidal anti-inflammatory drugs to flavonoids.

Inflammation is involved in increasing number of diseases necessitating the development of new, effective and safe treatments. Non steroidal anti-inflammatory drugs (NSAIDs) have been helpful in many instances, but they only inhibit cyclooxygenase (COX), but not the generation or actions of cytokines. Instead, some natural flavonoids have multiple anti-inflammatory effects, including COX inhibition, and a much safer profile. Increasing evidence indicates that inflammation plays a critical role in the pathogenesis of many diseases that also involve mast cells. Consequently, the need for new, effective and safe anti-inflammatory drugs is all the more urgent. Corticosteroids are quite potent, but have many adverse effects such as increased risk of infections, osteoporosis, glaucoma and depression. Biological agents such anti-TNF are useful in certain conditions, such as rheumatoid arthritis and psoriasis, but has been associated with increased risk of infection and leukemia.

Glioblastoma multiforme intraxial metastasis to the conus medullaris with primary disease under control: a rare unexpected finding.

We report on glioblastoma multiple spinal intraaxial metastases with primary disease radiologically under control. The case highlights glioblastoma biological behavior and spread mechanisms; dissemination may have occurred initially and been controlled by chemotherapy, or more likely, is an indicator that even if radiologically dormant, disease is unlikely biologically inactive.

MRI-derived radiomics to guide post-operative management of glioblastoma: Implication for personalized radiation treatment volume delineation.

Background: The glioblastoma's bad prognosis is primarily due to intra-tumor heterogeneity, demonstrated from several studies that collected molecular biology, cytogenetic data and more recently radiomic features for a better prognostic stratification. The GLIFA project (GLIoblastoma Feature Analysis) is a multicentric project planned to investigate the role of radiomic analysis in GB management, to verify if radiomic features in the tissue around the resection cavity may guide the radiation target volume delineation. Materials and methods: We retrospectively analyze from three centers radiomic features extracted from 90 patients with total or near total resection, who completed the standard adjuvant treatment and for whom we had post-operative images available for features extraction. The Manual segmentation was performed on post gadolinium T1w MRI sequence by 2 radiation oncologists and reviewed by a neuroradiologist, both with at least 10 years of experience. The Regions of interest (ROI) considered for the analysis were: the surgical cavity ± post-surgical residual mass (CTV_cavity); the CTV a margin of 1.5 cm added to CTV_cavity and the volume resulting from subtracting the CTV_cavity from the CTV was defined as CTV_Ring. Radiomic analysis and modeling were conducted in RStudio. Z-score normalization was applied to each radiomic feature. A radiomic model was generated using features extracted from the Ring to perform a binary classification and predict the PFS at 6 months. A 3-fold cross-validation repeated five times was implemented for internal validation of the model. Results: Two-hundred and seventy ROIs were contoured. The proposed radiomic model was given by the best fitting logistic regression model, and included the following 3 features: F_cm_merged.contrast, F_cm_merged.info.corr.2, F_rlm_merged.rlnu. A good agreement between model predicted probabilities and observed outcome probabilities was obtained (p-value of 0.49 by Hosmer and Lemeshow statistical test). The ROC curve of the model reported an AUC of 0.78 (95% CI: 0.68-0.88). Conclusion: This is the first hypothesis-generating study which applies a radiomic analysis focusing on healthy tissue ring around the surgical cavity on post-operative MRI. This study provides a preliminary model for a decision support tool for a customization of the radiation target volume in GB patients in order to achieve a margin reduction strategy.

Donor human milk versus mother's own milk in preterm VLBWIs: a case control study.

As for term infants, over the past decades there has been increasing evidence of the benefits of human milk in the feeding of Very Low Birth Weight Infants (VLBWI), influencing not only short-term health outcomes but also long-term neurodevelopmental, metabolic outcomes, and growth. Mother's own milk is the first choice for all neonates including preterm infants, when it is unavailable or in short supply, pasteurized donor breast milk offers a safe alternative and is considered the next best choice. The main aim of this case-control retrospective analysis was to evaluate short term advantages of mother's own milk as a sole diet compared to donor milk as a sole diet, in terms of growth, antiinfectious properties, feeding tolerance, NEC and ROP prevention in a population of VLBWI born in a tertiary center. We did not find significant differences in clinical outcome from mother's own milk compared with pasteurized donor milk. Only a slight and statistically not significant difference in growth could be observed, in favour of maternal milk. We conclude that the maximum effort should always be put in supporting and promoting breastfeeding and donor milk used not only as an alternative to mother's milk but also as a breastfeeding promotion and support strategy.

Auxological evaluation of newborns.

Auxological evaluation of the newborn should be based on accurate anthropometry at birth and a reliable estimate of gestational age (GA). However, a comprehensive evaluation of the neonate should consider not only anthropometric traits at birth, but also fetal ultrasound biometry and Doppler velocimetry. Many charts have been proposed, but they are hardly comparable with each other, due to numerous methodological problems. The Italian Societies of Neonatology, of Pediatric Endocrinology and Diabetology and the Italian Society of Medical Statistics and Clinical Epidemiology promoted a multicenter survey with the aim to produce an Italian neonatal anthropometric reference (Italian Neonatal Study [INeS] charts) fulfilling the set of the criteria that a reliable neonatal chart should possess. In order to construct an international standard, an international project (INTERGROWTH-21st) has started a study aiming to create a prescriptive standard. Until an international standard is developed, the use of national updated reference charts is recommended.

Medication and breastfeeding.

It is well accepted that the best feeding method for infants is breastfeeding, due to its numerous biological and clinical effects on child and maternal health. The use of medication by the nursing mother and the physician's advice to stop nursing are the most common reasons for the cessation of breastfeeding. The physician plays an extremely delicate role and should be able to assess risks and benefits for both mother and child. The main factors that must be taken into account include pharmacokinetics, the duration of maternal therapy, the age of the infant and the general health of the infant. All physicians should have access to reliable and updated information on medication safety during breastfeeding (reference books, online medical literature). Few drugs have been demonstrated to be absolutely contraindicated during breastfeeding. Nevertheless clear, safe and reliable information is still lacking for most drugs and it would be desirable to improve the knowledge about mechanisms and consequences of infant exposure to drug present in milk.

Critical appraisal of different anthropometric charts to evaluate postnatal growth of preterm infants.

Preterm infants' survival has greatly increased in the last few decades thanks to the improvement in obstetrical and neonatal care. The correct evaluation of postnatal growth of these babies is nowadays of primary concern, although the definition of their optimal postnatal growth pattern is still controversial. Concerns have also been raised about the strategies to monitor their growth, specifically in relation to the charts used. At present, the charts available in clinical practice are fetal growth charts, neonatal anthropometric charts and postnatal growth charts for term infants. None of these, for different reasons, is suitable to correctly evaluate preterm infant growth. Recently, an international project has recently started aiming to create prescriptive standard for the evaluation of postnatal growth of preterm infants (INTERGROWTH-21st). Alternatively, at present, while specific charts for evaluating preterm infant postnatal growth are lacking, the best compromise is likely to be as follows: from birth to term neonatal anthropometric charts; International longitudinal charts WHO 2006 or CDC 2002 from term to childhood.

Hyperbilirubinemia and management of breastfeeding.

Hyperbilirubinemia and jaundice are natural, physiological phenomena which are only to be expected in the neonatal period, within certain limits. The highest percentage of jaundice in breastfed newborns should be evaluated in connection with inadequate management of breastfeeding rather than a direct effect of breast milk. Breastfeeding is also linked to visible jaundice persisting beyond the first two weeks of life (“breast milk jaundice”), but the appearance of skin jaundice is not a reason for interrupting breastfeeding which can and should continue without any interruption in most cases. There have been numerous contributions to the literature which have rescaled the direct role of breast milk both in early jaundice and in the more severe cases of late jaundice. The reviewed guidelines for detection and management of hyperbilirubinemia underline how prevention of badly managed breastfeeding and early support for the couple mother-child are effective prevention measures against severe early-onset jaundice; furthermore, the breastfeeding interruption is no longer recommended as a diagnostic procedure to identify breast milk jaundice because of its low specificity and the risk to disregarding the detection of a potentially dangerous disease.

Metabolism and biological functions of human milk oligosaccharides.

It is well known that breastfeeding is beneficial both for its nutritional properties and for the presence of biologically active compounds. Among these, human milk oligosaccharides (HMOs), representing the third largest fraction of human milk, have been assigned important biological functions, such as prebiotic and immunomodulatory and antimicrobial effects. HMOs are synthesized in the mammary gland by glycosyltransferase enzymes and can be divided in core-oligosaccharides, sialo-oligosaccharides, fucosyl-oligosaccharides and sialo-fucosyl-oligosaccharides on the basis of their chemical structure. Glycosyltransferases enzymes are partially regulated by genetic mechanisms; according to the expression of secretory and Lewis' genes, it is possible to classify human milk in 4 different secretory groups. We hereby present a review of the current knowledge concerning HMOs, their metabolism and main biological functions.

Relationship between sleep/wakefulness and gastroesophageal reflux in symptomatic newborns.

The state of sleep/wakefulness is well known to influence esophageal acid exposure and the number of acid refluxes whereas it is uncertain whether the same is true of the non-acid refluxes that predominate in the newborns. To investigate the relationship between sleep/wakefulness and refluxes 45 newborns with gastroesophageal reflux symptoms were studied with combined multichannel intraluminal impedance and pH monitoring. We found that sleep/wakefulness influenced acid and weakly acidic reflux frequency (awake 2.6+/-0.8; asleep 2.1+/-1.1; p=0.006). A negative correlation was found between sleepness periods and the mean reflux duration for both acid (R=0.55;p < 0.001) and weackly acidic (R=0.51;p < 0.001) refluxes. This finding may raise some concerns about the over-prescription of antacid drugs in newborns.