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Abstract Mosaic chromosomal anomalies arising in the product of conception and the final fetal chromosomal arrangement are expression of complex biological mechanisms. The rescue of unbalanced chromosome with selection of the most viable cell line/s in the embryo and the unfavourable imbalances in placental tissues was documented in our previous paper and in the literature. We report four additional cases with mosaic derivative chromosomes in different feto-placental tissues, further showing the instability of an intermediate gross imbalance as a frequent mechanism of de novo cryptic deletions and duplications. In conclusion we underline how the extensive remodeling of unbalanced chromosomes in placental tissues represents the ‘backstage’ of de novo structural rearrangements, as the early phases of a long selection process that the genome undergo during embryogenesis.

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder characterized by the predisposition to develop tumors such as malignant peripheral nerve sheath tumors (MPNSTs) which represents the primary cause of death for NF1-affected patients. Regardless of the high incidence and mortality, the molecular mechanisms underneath MPNST growth and metastatic progression remain poorly understood. In this proof-of-concept study, we performed somatic whole-exome sequencing (WES) to profile the genomic alterations in four samples from a patient with NF1-associated MPNST, consisting of a benign plexiform neurofibroma, a primary MPNST, and metastases from lung and skin tissues. By comparing genomic patterns, we identified a high level of variability across samples with distinctive genetic changes which allow for the definition of profiles of the early phase with respect to the late metastatic stages. Pathogenic and likely pathogenic variants were abundant in the primary tumor, whereas the metastatic samples exhibited a high level of copy-number variations (CNVs), highlighting a possible genomic instability in the late phases. The most known MPNST-related genes, such as TP53 and SUZ12, were identified in CNVs observed within the primary tumor. Pathway analysis of altered early genes in MPNST pointed to a potential role in cell motility, division and metabolism. Moreover, we employed survival analysis with the TCGA sarcoma genomic dataset on 262 affected patients, in order to corroborate the predictive significance of the identified early and metastatic MPNST driver genes. Specifically, the expression changes related to the mutated genes, such as in RBMX, PNPLA6 and AGAP2, were associated with reduced patient survival, distinguishing them as potential prognostic biomarkers. This study underlines the relevance of integrating genomic results with clinical information for early diagnosis and prognostic understanding of tumor aggressiveness.

Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine cancer that usually affects the elderly and immunosuppressed in sun-exposed areas. Due to its rarity, it is frequently unrecognized, and its management is not standardized across medical centers, despite the more recent availability of immunotherapy, with avelumab as first-line treatment improving the prognosis even in advanced stages of disease. We conducted a purpose-designed survey of a selected sample of physicians working in the Lazio region, in Italy, to assess their awareness and knowledge of MCC as well as their perspective on assisted diagnostic and therapeutic pathways. The Lazio region, and in particular Rome, is one of the most important academic and non- academic center in Italy dedicated to the diagnosis and treatment of skin cancer. A total of 368 doctors (including 100 general practitioners, 72 oncologists, 87 dermatologists, 59 surgeons, and 50 anatomopathologists) agreed to be part of this survey. Surgeons, oncologists, and dermatologists thought themselves significantly more updated on MCC than primary care physicians, but more than half of the interviewees are interested in CCM training courses and training with clearer and more standardized care pathways. Significant differences have been reported from survey participants in terms of multidisciplinary team set up for MCC management. The identification of specialized centers and the improvement of communication pathways among different specialties, as well as between patients and physicians, could be very beneficial in improving patients’ journey modeling and starting a uniform diagnostic and therapeutic pathway for MCC patients in the new era of immunotherapies.

Background: The aim of our study was to comparatively assess volume changes related to daily occupation of the whole leg (WLv), of the lower leg (LLv) and of the upper leg (ULv) in subject with no venous and lymphatic disorders. Method: WLv, LLv, and Ulv were evaluated by water displacement volumetry (WDV) in the morning and in the evening in 20 healthy subjects. Results: In the legs with occupational edema (OE), WLv increased by 7.07%, LLv by 5.25%, and ULv by 9.80%. In legs without clear OE, WLv increased by 2.41%, LLv by 1.35, and ULv by 3.38%. Conclusions: Surprisingly, the increase of ULv was greater than that of LLv. An evening increase in the leg volume also occurred in legs with no clear OE. In our series, a clinically evident OE was related to an increase of the WLv, LLv, and ULv greater than 5.83%, 8.68%, and 1.88%, respectively. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder characterized by the predisposition to develop tumors such as malignant peripheral nerve sheath tumors (MPNSTs) which represents the primary cause of death for NF1-affected patients. Regardless of the high incidence and mortality, the molecular mechanisms underneath MPNST growth and metastatic progression remain poorly understood. In this proof-of-concept study, we performed somatic whole-exome sequencing (WES) to profile the genomic alterations in four samples from a patient with NF1-associated MPNST, consisting of a benign plexiform neurofibroma, a primary MPNST, and metastases from lung and skin tissues. By comparing genomic patterns, we identified a high level of variability across samples with distinctive genetic changes which allow for the definition of profiles of the early phase with respect to the late metastatic stages. Pathogenic and likely pathogenic variants were abundant in the primary tumor, whereas the metastatic samples exhibited a high level of copy-number variations (CNVs), highlighting a possible genomic instability in the late phases. The most known MPNST-related genes, such as TP53 and SUZ12, were identified in CNVs observed within the primary tumor. Pathway analysis of altered early genes in MPNST pointed to a potential role in cell motility, division and metabolism. Moreover, we employed survival analysis with the TCGA sarcoma genomic dataset on 262 affected patients, in order to corroborate the predictive significance of the identified early and metastatic MPNST driver genes. Specifically, the expression changes related to the mutated genes, such as in RBMX, PNPLA6 and AGAP2, were associated with reduced patient survival, distinguishing them as potential prognostic biomarkers. This study underlines the relevance of integrating genomic results with clinical information for early diagnosis and prognostic understanding of tumor aggressiveness. [ABSTRACT FROM AUTHOR]

Objectives: The occurrence of leg edema in patients with chronic venous disease (CVD) is currently evaluated by visual inspection, palpation, and measurement of limb circumference. The changes of soft tissues morphology in swollen legs have been poorly investigated by ultrasonography (US) in the past. The purpose of this study was to evaluate the effects of medical compression stockings (MCS) on the US morphology of the cutaneous and subcutaneous layers (CL and SCL, respectively) in legs with venous edema. Methods: The morphology of the cutaneous and subcutaneous layers (CL and SCL) was evaluated by US in 18 swollen legs with chronic venous disorders (CVD), before and after 4 weeks of treatment with MCS. Skin morphology was evaluated by using an 8–14 MHz probe with a dedicated setting, 5 cm above the medial malleolus. Results: MCS provoked both quantitative and qualitative changes. A reduction of CL/SCL thickness greater than 20% was observed in 16/18 legs. A reduction of the SCL echogenicity was observed in 14/18 legs. Nine out of 12 legs which showed abnormalities of the CL before treatment showed a structural rearrangement of the dermis and the reappearing of the dermo–hypodermic junction. Conclusions: The reduction of the SCL thickness is to be ascribed to the increase of veno-lymphatic drainage promoted by MCS. The reduction of tissue echogenicity by MCS is a quite innovative concept and it is suggestive for an anti-inflammatory action of MCS on skin tissues. [ABSTRACT FROM AUTHOR]

Background: The decision to treat a refluxing anterior saphenous vein (ASV) should be a clinical decision based on the assessment on the ASV's contribution to patient's signs and symptoms. Once the decision to treat has been made, there are anatomic, clinical, and technical considerations in treatment planning. Methods: Clinical scenarios were discussed by a panel of experts and common anatomic, clinical, and technical considerations were identified. Results: There are unique clinical considerations such as whether both the great saphenous vein (GSV) and ASV should be concomitantly treated, if a normal ASV should be treated when treating a refluxing GSV and when and how to treat the associated tributary varicose tributaries. Being aware of the anatomic, clinical, and technical considerations allows development of a treatment plan that optimizes long-term outcomes in patients with ASV reflux. Conclusion: Ultimately the treatment plan should be tailored to address these types of variables in a patient-centered discussion. [ABSTRACT FROM AUTHOR]

Background: Strain gauge plethysmography (SGP) is employed to evaluate venous drainage of the lower leg. Methods: In this study, SGP was used to evaluate the effects of the hydrostatic pressure (HP) of water on venous volume (VV), expelled volume, and ejection fraction (EF) in 22 healthy legs before and during immersion in water. Results: HP reduced VV by 100% and even more during underwater (UW) exercise, making calculation of the UW EF possible. Discussion: UW SGP is feasible and indicates that HP improves venous haemodynamics. This study suggests that including UW leg exercise in the rehabilitation protocols of patients with chronic venous disease may be useful. Keywords: Strain gauge plethysmography, Underwater compression, Underwater ejection fraction, Underwater venous volume.

Facial rejuvenation procedures to circumvent traditional surgery have become increasingly popular to promote a youthful appearance with minimally invasive procedures such as injectable botulinum toxin, soft-tissue fillers, and chemical peels. Nevertheless, complications can occur even with an astute and experienced injector. Here we present the case of a patient who underwent static lip reanimation using a dermoadiposal flap for right facial nerve damage following nodule removal as a filler complication. A "modified bulls horn approach" to the upper lip lift was performed around the nasal wings and columella and along the right nasolabial fold. The flap was de-epithelized and harvested. Using the open tip of a small liposuction cannula, the distal portion of the flap was tunneled and fixed directly in a C-loop fashion using U stitches, transfixing the flap to the periosteum of the zygomatic arch. At 3 years follow-up, no significant complications were observed, and the patient reported no functional limitations or dissatisfaction with the scars in the nasolabial fold or around the nasal wings and columella.

Verrucous hyperplasia of the skin rarely occurs in legs with severe venous stasis. In these cases, ultrasound demonstrated thickening and hyperechogenicity of the skin layers. The core of the verrucous-like protrusions consisted of a fibrous lump of the reticular dermis, surrounded by an anechogenic layer and covered by a thickened epidermal shell. Compression treatment provokes the progressive disappearance of the dermal plications, accompanied by reduction of the cutaneous and subcutaneous edema and infiltration. Ultrasound easily demonstrates the histologic changes of verrucous hyperplasia of the skin and allows evaluation of the evolution of the disease and the efficacy of treatments. Keywords: Skin ultrasound, Verrucous skin hyperplasia, Venous stasis, Compression treatment

Tectonic activity in the Mediterranean area (involving migrations of old orogenic belts, formation of basins and building of orogenic systems) has been determined by the convergence of the confining plates (Nubia, Arabia and Eurasia). Such convergence has been mainly accommodated by the consumption of oceanic and thinned continental domains, triggered by the lateral escapes of orogenic wedges. Here, we argue that the implications of the above basic concepts can allow plausible explanations for the very complex time-space distribution of tectonic processes in the study area, with particular regard to the development of Trench-Arc-Back Arc systems. In the late Oligocene and lower–middle Miocene, the consumption of the eastern Alpine Tethys oceanic domain was caused by the eastward to SE ward migration/bending of the Alpine–Iberian belt, driven by the Nubia–Eurasia convergence. The crustal stretching that developed in the wake of that migrating Arc led to formation of the Balearic basin, whereas accretionary activity along the trench zone formed the Apennine belt. Since the collision of the Anatolian–Aegean–Pelagonian system (extruding westward in response to the indentation of the Arabian promontory) with the Nubia-Adriatic continental domain, around the late Miocene–early Pliocene, the tectonic setting in the central Mediterranean area underwent a major reorganization, aimed at activating a less resisted shortening pattern, which led to the consumption of the remnant oceanic and thinned continental domains in the central Mediterranean area.

Objectives: Hydrostatic compression (HC) occurring during body immersion is considered beneficial for venous return from the lower limbs. No study has evaluated the effects of HC on the veins of the lower limbs using duplex ultrasound (DU). The purpose of this study was to use DU to evaluate the morphology and flow of the leg veins during immersion. Design: The femoral and great saphenous veins were evaluated before and during immersion in a specifically built pool, in normal and varicose limbs. Results: HC reduces vein size in both normal and varicose limbs. During immersion spontaneous flow increases whereas when present, blood reflux decreases. Discussion: This pilot, proof of concept study has demonstrated the feasibility of DU investigation of leg veins during immersion. Larger series of underwater DU evaluations of normal and varicose legs are necessary to quantify and better explain the effects of HC on the veins of the lower limb. Keywords: Duplex ultrasound, Underwater duplex, Varicose veins, Compression, Balneotherapy, Venous haemodynamics