Alopecia neoplastica as a sign of visceral malignancies: a systematic review.

Alopecia neoplastica (AN) from visceral tumours is a rare form of cutaneous metastasis in which internal malignancies spread to the scalp. The diagnosis of AN may be very challenging, especially when its onset precedes the diagnosis of the primary tumour. We aimed to improve the knowledge on AN, highlighting that in case of scarring localized alopecia, a differential diagnosis with metastasis should always be considered. We performed a systematic review to describe the main demographic and clinical features associated with AN from visceral malignancies; a survival analysis was also performed. In 118 reports, accounting for 123 patients, we found that women were more affected by AN than men (53.7% vs. 46.3%). The most frequent site of the primary tumour was the gastrointestinal tract (24.4%), followed by breast (17.9%), kidney (8.1%), lung (7.3%), thyroid (7.3%), uterus (6.5%), central nervous system (6.5%), liver (3.3%) and other anatomic areas for 18.7% of cases. Furthermore, in more than half of the cases (66.1%), AN lesions were single and were mainly diagnosed after the primary visceral tumour (71.5%). Finally, survival analysis highlighted a lower progression-free survival in men; while, no significant differences in overall survival were reported among genders. In conclusion, metastatic skin disease should always be taken into consideration when dealing with patients with localized scarring alopecia.

Suicide of isolated inmates suffering from psychiatric disorders: when a preventive measure becomes punitive.

We performed external autopsies and examinations on two inmates who had committed suicide by hanging themselves with their underwear and using the window bars of their cells as ligature points after they had been placed in solitary confinement. In one case, the inmate had even been deprived of her clothing (with the exception to her underwear). Underwear has been rarely described as a means for self-harm and, to the best of our knowledge, no previous study has focused on cases of prison suicides committed using this garment, even though it is available to every inmate. The two cases were very similar; both inmates were young, physically aggressive and in their first week at a new facility; both had been affected by mental disorders, had been prescribed psychotropic medications and had histories of psychiatric hospitalisation. In each case, the psychiatric evaluations had highlighted significant suicidal risk. We discuss these two cases in an attempt to describe the complexity of and contradictions within the management of suicidal inmates at correctional facilities. We aim to propose new strategies and emphasise the need to introduce evidence-based standardised protocols over inhumane, ineffective and simplistic punitive measures in the management of these individuals.

Vasculitides with cutaneous expression in children: clinico-pathological correlations.

The most recent pediatric vasculitis classifications (EULAR/PRINTO/PRES) have proposed the use of an integration of clinical signs and symptoms, laboratory data, imaging and pathologic data. Pediatric vasculitis represent a peculiar clinical-diagnostic model, compared to the corresponding adult pathology chapter, and in particular, dermatopathologic aspects of these diseases identify more specific issues, made contingent by crucial variables such as duration of vasculitis lesion, site of the biopsy, proper biopsy depth, and possibility to correlate histopathological findings with immunopathological results. Possible additional diagnostic difficulties may arise from the fact that, in children, the same systemic disease, such as lupus erythematosus, may present with different clinical manifestations, with histopathological features of a precise type of vasculitis specific for that type of clinical manifestation. Examples are provided by hypocomplementemic urticarial vasculitis, cryoglobulinemic purpura, lymphocytic vasculitis of livedoid lesions. This paper describes the cutaneous histopathological findings of some vasculitis related pediatric diseases, be they pertaining to a systemic vasculitis with corresponding cutaneous vasculitis, to a systemic vasculitis with sporadic cutaneous vasculitic involvement, and to a systemic vasculitis without cutaneous vasculitic involvement. Type and level of histopathological vasculitic involvement, caliber of the vessel, type of vasculitis associated infiltrate, are likewise reliable integration in the complex diagnostic path of vasculitis in childhood. On the basis of these criteria dermatopathologists should be confident in identifying the type of the vasculitis and relate them to a specific pediatric disease.

The c.480C>G polymorphism of hOCT1 influences imatinib clearance in patients affected by chronic myeloid leukemia.

The aim of the study was to investigate any possible influence of polymorphisms of transmembrane transporters human organic cation transporter 1 (hOCT1), ABCB1, ABCG2 on imatinib pharmacokinetics in 33 men and 27 women (median age and range, 56 and 27-79 years, respectively) affected by chronic myeloid leukemia. A population pharmacokinetic analysis was performed to investigate imatinib disposition in every patient and the role of transporter polymorphisms. Results showed that the α1-acid glycoprotein and the c.480C>G genotype of hOCT1 had a significant effect on apparent drug clearance (CL/F) being responsible, respectively, for a 20% and 10% decrease in interindividual variability (IIV) of CL/F (from 50.1 up to 19.6%). Interestingly, 25 patients carrying at least one polymorphic c.480 G allele had a significant lower CL/F value with respect to the 35 c.480CC individuals (mean±s.d., 9.6±1.6 vs 12.1±2.3 l h(-1), respectively; P<0.001). In conclusion, the hOCT1 c.480C>G SNP may significantly influence imatinib pharmacokinetics, supporting further analyses in larger groups of patients.

Pompholyx of the hands after intravenous immunoglobulin therapy for clinically isolated syndrome: a paediatric case.

Pompholyx is a common eruption of small vesicles on the palms, soles, and/or lateral aspects of the fingers. It has a multifactorial etiology, including genetic determinants, allergy to metals, and id reaction; rarely it is a drug-related side effect. We report a paediatric case of pompholyx of the hands related to the intravenous immunoglobulin (IVIG) therapy for Clinically Isolated Syndrome (CIS). A 10-year-old boy, received an IVIG therapy (Venital, Kedrion Spa, Italy) at a dose of 400 mg/kg daily for five days. The fifth day of IVIG infusion, a symmetrical vesicular eruption appeared on the palms of the hands and on lateral aspects of the fingers. The lesions improved with application of topical steroids in few days. The mechanism of induction of pompholyx by IVIG therapy is unknown. A review of the Literature suggests the hypothesis that dyshidrotic eczematous reactions may be related not only to the type of IVIG, to the dose and the rates of infusion, but also to an allergic response to excipients and preservatives contained in the drug, probably elicited by an underlying neurological disease in some cases.

Panniculitis in children.

This paper will give a comprehensive view of the most frequent panniculitides seen in childhood, with emphasis on the types exclusively found in infancy, and for all other types of panniculitides also found in adults. Aim of this paper is also to analyze the clinical differences between panniculitis in childhood and in adulthood, and to give reliable histopathologic criteria for a specific diagnosis. A review of the literature is here integrated by authors' personal contribution. Panniculitides in children is a heterogeneous group of diseases, as well as in adult life, characterized by inflammation of the subcutaneous fat. Only very few types of panniculitis are exclusively found in childhood, such as Sclerema neonatorum and subcutaneous fat necrosis of the newborn, while the vast majority of the other types may be found both in paediatric age and in adults. Furthermore, this paper will consider in detail panniculitis according to their frequency, such as Erythema nodosum, Lupus panniculitis, Cold panniculitis, panniculitis in Behçet disease, and poststeroid panniculitis. It will also describe rare forms of panniculitis, such as Eosinophilic panniculitis (a pathological entity debated by many authors), Subcutaneous panniculitis T-cell lymphoma, and the different forms of the so call "Lipophagic panniculitis", encompassing respectively the febrile relapsing panniculitis of Weber-Christian disease and the non-relapsing form of Rothmann-Makai disease. For each type of panniculitis considered concise information will be given about epidemiology, etiology, clinical findings, laboratory data, prognosis and therapy, while histopathologic findings will be described in detail.

Post-surgical lipophagic panniculitis: a specific model of traumatic panniculitis and new histopathological findings.

Aim of this work was to define the histopathological features of post-surgical panniculitis. Dermal and hypodermal changes will be analyzed in detail, to understand the cascade of events that characterize the tissue response to surgical trauma. Cutaneous re-excision specimens of cases of basal cell carcinoma, squamous cell carcinoma, and melanoma consecutively seen from January 1, 2011 to June 30, 2011 at the Department of Dermatology, University of Pavia, were included in this study. Only the cases in which the first surgical procedure included the subcutaneous fat, were considered. In addition, the time elapsed from the first surgical procedure and the re-excision had to be included in a period of time from one to three months. All the specimens were stained with hematoxylin and eosin. Thirty cutaneous re-excision specimens were studied. Histopathologic examination revealed changes of epidermis, ranging from slight atrophy to moderate hyperplasia. In two cases focal ulceration was seen, with transfollicular elimination of foreign body material. The main dermal changes observed were the: 1) scar with well defined vertical orientation along the dermal suture line; 2) rounded cicatricial areas with radial branching septa of scarring tissue; 3) foreign body granuloma formation; 4) alignment of hystiocytes at the dermo-hypodermal border; 5) traumatic neuromas. The subcutaneous fat changes included: 1) lobular panniculitis with consistent presence of foam cells; 2) striking anisocytosis with pseudocystic degeneration and necrosis of adipocytes; 3) eritrocyte extravasation, mainly at the dermo-hypodermal border; 4) deep seated phlebitis. Post-surgical panniculitis is a lobular foam cell panniculitis characterized by simultaneous dermal and hypodermal changes, expression of the multi-faceted tissue response to a surgical trauma. This type of peculiar lipophagic response puts post-surgical panniculitis into the wider chapter of lipophage tissue response seen in atherosclerosis, glomerulosclerosis and some infectious models such as Mycobacterium tuberculosis and Chlamydia pneumoniae infections. Furthermore it may be seen as a reliable and convenient model for laboratory investigation on foam cell tissue response.

Ethical and medico-legal issues of TOETVA procedure and simulation on cadavers: a scoping review.

Conventional open thyroidectomy is still considered the gold standard for thyroid surgery. Transoral endoscopic thyroidectomy vestibular approach (also known as TOETVA) is often considered to be more advantageous than the other approaches, such as minimally invasive video assisted thyroidectomy, thyroidectomy via breast/axillary/retroauricular access, bilateral axillo-breast approach and axillo-bilateral breast approach. In this scoping review, we discuss the risks and the benefits of this surgical approach and its medico-legal and ethical implications, particularly focusing on the importance of practice on cadavers. Currently, there is little scientific evidence supporting TOETVA, since there are few papers on the comparison with the traditional open thyroidectomy that have been published and thus little data on the long-term outcomes of TOETVA are available. Since the better cosmetic outcome currently represents the main indication for this surgical technique, substantial medico-legal and ethical issues arise. Moreover, practice on cadavers can help surgeons to develop the technical and non-technical skills required to perform efficiently and safely this new surgical procedure.

Household disinfectant exposure during the COVID-19 pandemic: a retrospective study of the data from an Italian poison control center.

OBJECTIVE: Since the beginning of the COVID-19 pandemic it has been recommended that chemical disinfectants are used to protect surfaces. This study aimed to determine whether the number of exposure calls related to household disinfectants (HD) received between January 30, 2020 to May 18, 2020 varied from the same time period in the previous year. MATERIALS AND METHODS: A retrospective review of the poison control center database from the Fondazione Universitario Policlinico Agostino Gemelli IRCCS, Rome, Italy, was conducted. Calls from Italian citizens, hospitals, and general practitioners received during the same time period in 2019 and 2020 were compared. RESULTS: The center received 1972 exposure calls during the study period. A 5% increase in calls regarding exposure to HDs was noted from 2019 to 2020 (9.8% to 15.2%, p<0.001). The majority of enquiries regarded bleach-containing products, hand sanitizers, ethanol, and hydrogen peroxide. Most calls were received from patients in their homes (n, 259; prevalence, 86%; increase, 107%) and concerned accidental exposure (n, 280; prevalence, 93%; increase, 76%), while cases of intentional exposure decreased (n, 14; prevalence, 5%; decrease, 33%). The main route of exposure was ingestion (n, 170; prevalence, 57%; increase, 45%), but the highest increase was observed in inhalation cases (n, 82; prevalence, 27%; increase, 122%). CONCLUSIONS: As the incidence of enquiries regarding products that can represent an important health hazard, when improperly used, increased in 2020 suggests that the COVID-19 public health messaging on the proper use of HDs should be improved.

An enigmatic case of cardiac death in an 18-years old girl.

We report a case of unusual and unexplained cardiac death in an 18-years old female patient with congenital neurosensorial deafness. The fatal event was characterized by an initial syncopal episode, associated with a wide QRS tachycardia (around 110 bpm) but stable hemodynamic conditions. The patient, however, subsequently developed severe hypotension and progressive bradyarrhythmias until asystole and lack of cardiac response to resuscitation maneuvers and ventricular pacing.

Diagnostic value of endoscopic markers for celiac disease in adults: a multicentre prospective Italian study.

AIM: Some endoscopic features of duodenal mucosa are marker of mucosal injury, the most common cause being celiac disease (CD). The aim of this study was to prospectively assess the diagnostic value of the endoscopic markers for the diagnosis of CD in the adult population undergoing routine upper endoscopy. METHODS: This was a prospective multicenter study conducted at 37 Italian endoscopic centers. A total of 509 consecutive patients submitted to routine upper endoscopy who presented one or more of following endoscopic markers were included: 1) mucosal mosaic pattern in the bulb and/or descending duodenum (DD); 2) nodularity in the bulb and/or DD; 3) scalloping of Kerkring's folds; 4) reduction in the number or absence of folds in the DD. 4 biopsies samples were taken from descending duodenum. In patients with histological findings consistent with CD, according to Oberhuber classification, sierologic test (EMA, tTGA) were performed for confirm the diagnosis. RESULTS: At endoscopy, 249 patients showed an isolated marker; 260 subjects showed a coexistence of more than one marker; 369 patients (72.5%) presented mucosal lesions at histological examination and in 347 of these patients the diagnosis of CD was confirmed by serologic markers (94.0%). For 10 patients the diagnosis remained uncertain because of negative sierology and exclusion of other other cause of mucosal lesions. The diagnosis of CD was made in 61.3% patients who showed the mosaic pattern, in 65.7% of patients with nodular mucosa, in 64.4% of patients with scalloping of folds, in 40.2% of patients with reduction of folds, and in 61.5% of patients with loss of folds and in 83.6% of patients who showed the coexistence of more than one marker. The endoscopic markers overall had a PPV of 68% for the diagnosis of CD; the markers that singularly have demonstrated a higher correlation with CD are: mosaic mucosa of DD (PPV 65.0%), nodular mucosa of the bulb and DD (PPV 75.5%), and scalloping of folds (PPV 64.4%). CONCLUSION: The study confirms the important role of endoscopy in the diagnostic process of CD not only for the bioptic sampling in patients with clinical suspicion of CD, but especially for the opportunity to evaluate alterations of the duodenal mucosa suggestive of CD in the general population and, consequently, to identify those patients who should undergo a duodenal biopsy.

Ficoll-hypaque separation vs whole blood lysis: Comparison of efficiency and impact on minimal residual disease analysis.

INTRODUCTION: The high-throughput era remarkably changed molecular laboratory practice. Actually, the increasing number of processed samples requires to reduce the risk of operator biases, by automating or simplifying as much as possible both the analytical and the pre-analytical phases. Minimal residual disease (MRD) studies in hematology often require a simultaneous processing of many bone marrow and peripheral blood samples from patients enrolled in prospective, multicenter, clinical trials, monitored at several planned time points. METHODS: In this study, we demonstrate that red blood cell lysis (RBL) pre-analytical procedure can replace the time-consuming Ficoll stratification as cell recovering step. Here, we show a MRD comparison study using both total white blood cells and mononuclear cells recovered by the 2 procedures from 46 follicular lymphoma (FL), 15 multiple myeloma (MM), and 11 mantle cell lymphoma (MCL) patients enrolled in prospective clinical trials. RESULTS: The experiments were performed in the 4 laboratories of the Fondazione Italiana Linfomi (FIL) MRD Network and showed superimposable results, in terms of good correlation (R = 0.87) of the MRD data obtained by recovering blood cells by the 2 approaches. CONCLUSION: Based on these results, the FIL MRD Network suggests to optimize the pre-analytical phases introducing RBL approach for cell recovery in the clinical trials including MRD analysis.

Stoichiometry of Na+-HCO-3 cotransport in basolateral membrane vesicles isolated from rabbit renal cortex.

The major pathway for HCO3- transport across the basolateral membrane of the proximal tubule cell is electrogenic Na+-HCO3- cotransport. In this study, we have determined the stoichiometry of the Na+-HCO3- cotransport system in basolateral membrane vesicles that were isolated from rabbit renal cortex by Percoll gradient centrifugation. When the membrane potential is approximated by the Nernst potential for K+, as in the presence of the K+ ionophore valinomycin, equilibrium thermodynamics predicts that the Na+-HCO3- cotransport system should come to equilibrium and mediate no net flux when (Na)i/(Na)o = [(HCO3)o/(HCO3)i]n[(K)o/(K)i]n-1, where n is the HCO3-:Na+ stoichiometry. Our experimental approach was to impose transmembrane Na+, HCO3-, and K+ gradients of varying magnitude and direction, and then to measure the net flux of Na+ over the subsequent 3-s period. In this way, we could determine the conditions for equilibrium of the transport system and thereby calculate n. The results of these experiments indicate that the value of n is greater than 2.6 and less than 3.5, consistent with a stoichiometry of 3 HCO3-:1 Na+, or a thermodynamically equivalent process. Based on reported intracellular potentials and ion activities, this value for the stoichiometry indicates that the inside-negative membrane potential is sufficient to drive HCO3- exit against the inward concentration gradients of HCO3- and Na+ that are present across the basolateral membrane of the intact proximal tubule cell under physiologic conditions.

ACP1 and offspring sex ratio in smoking puerperae: a study at population level.

BACKGROUND: Data from previous study by our group suggest that in smoking women sex ratio of offspring is higher in newborns carrying ACP1C allele than in other ACP1 genotypes, suggesting that differences observed among human population concerning the effect of smoking may depend in part on this genetic factor. OBJECTIVES: In order to further explore this issue we have studied another population and have analysed the relationship between sex ratio and ACP1C gene frequency at population level. METHODS: The analysis includes 719 consecutive births from Central Italy considered in a previous paper and 5510 consecutive births from Sardinia. Data from English and Japanese populations have also been considered in the analysis. RESULTS: Among newborns not carrying ACP1C there is a decrease of SR among the offspring of smoking mothers, while among newborns carrying the ACP1C allele there is an increase of SR among the offspring of smoking mothers relative to non-smoking mothers. Considering Sardinian, Italian, English and Japanese population there is a linear positive relationship between C allele frequency and SR in smoking mothers. CONCLUSIONS: The present observation suggests an interaction between smoking and ACP1 regarding their effects on sex ratio, by which the presence of the ACP1C allele appears to counteract the effect of smoking. This suggests that genetic background may modify the effects of toxic environmental factors on gamete production and functionality and/or on intrauterine survival.

Synaptic plasticity in the medial vestibular nuclei: role of glutamate receptors and retrograde messengers in rat brainstem slices.

The analysis of cellular-molecular events mediating synaptic plasticity within vestibular nuclei is an attempt to explain the mechanisms underlying vestibular plasticity phenomena. The present review is meant to illustrate the main results, obtained in vitro, on the mechanisms underlying long-term changes in synaptic strength within the medial vestibular nuclei. The synaptic plasticity phenomena taking place at the level of vestibular nuclei could be useful for adapting and consolidating the efficacy of vestibular neuron responsiveness to environmental requirements, as during visuo-vestibular recalibration and vestibular compensation. Following a general introduction on the most salient features of vestibular compensation and visuo-vestibular adaptation, which are two plastic events involving neuronal circuitry within the medial vestibular nuclei, the second and third sections describe the results from rat brainstem slice studies, demonstrating the possibility to induce long-term potentiation and depression in the medial vestibular nuclei, following high frequency stimulation of the primary vestibular afferents. In particular the mechanisms sustaining the induction and expression of vestibular long-term potentiation and depression, such as the role of various glutamate receptors and retrograde messengers have been described. The relevant role of the interaction between the platelet-activating factor, acting as a retrograde messenger, and the presynaptic metabotropic glutamate receptors, in determining the full expression of vestibular long-term potentiation is also underlined. In addition, the mechanisms involved in vestibular long-term potentiation have been compared with those leading to long-term potentiation in the hippocampus to emphasize the most significant differences emerging from vestibular studies. The fourth part, describes recent results demonstrating the essential role of nitric oxide, another retrograde messenger, in the induction of vestibular potentiation. Finally the fifth part suggests the possible functional significance of different action times of the two retrograde messengers and metabotropic glutamate receptors, which are involved in mediating the presynaptic mechanism sustaining vestibular long-term potentiation.

Contribution of self-motion perception to acoustic target localization.

CONCLUSION: The findings of this study suggest that acoustic spatial perception during head movement is achieved by the vestibular system, which is responsible for the correct dynamic of acoustic target pursuit. OBJECTIVE: The ability to localize sounds in space during whole-body rotation relies on the auditory localization system, which recognizes the position of sound in a head-related frame, and on the sensory systems, namely the vestibular system, which perceive head and body movement. The aim of this study was to analyse the contribution of head motion cues to the spatial representation of acoustic targets in humans. MATERIAL AND METHODS: Healthy subjects standing on a rotating platform in the dark were asked to pursue with a laser pointer an acoustic target which was horizontally rotated while the body was kept stationary or maintained stationary while the whole body was rotated. The contribution of head motion to the spatial acoustic representation could be inferred by comparing the gains and phases of the pursuit in the two experimental conditions when the frequency was varied. RESULTS: During acoustic target rotation there was a reduction in the gain and an increase in the phase lag, while during whole-body rotations the gain tended to increase and the phase remained constant. The different contributions of the vestibular and acoustic systems were confirmed by analysing the acoustic pursuit during asymmetric body rotation. In this particular condition, in which self-motion perception gradually diminished, an increasing delay in target pursuit was observed.