Two-year multidisciplinary follow-up of COVID-19 patients requiring invasive and noninvasive respiratory support.

BACKGROUND: COVID-19 patients frequently develop respiratory failure requiring mechanical ventilation. Data on long-term survival of patients who had severe COVID-19 are insufficient. We assessed and compared two-year survival, CT imaging, quality of life, and functional recovery of COVID-19 ARDS patients requiring respiratory support with invasive (IMV) versus noninvasive ventilation (NIV). METHODS: Patients with COVID-19 pneumonia admitted up to May 28th, 2020, who required IMV or NIV, and survived to hospital discharge were enrolled. Patients were contacted two years after discharge to assess vital status, functional, psychological, and cognitive outcomes using validated scales. Patients with persistent respiratory symptoms or high burden of residual lung damage at previous CT scan received a two-year chest CT scan. RESULTS: Out of 61 IMV survivors, 98% were alive at two-year follow-up, and 52 completed the questionnaire. Out of 82 survivors receiving NIV only, 94% were alive at two years, and 47 completed the questionnaire. We found no major differences between invasively and noninvasively ventilated patients, with overall acceptable functional recovery. Among the 99 patients completing the questionnaire, 23 have more than moderate exertional dyspnea. Chest CT scans showed that 4 patients (all received IMV) had fibrotic-like changes. CONCLUSIONS: Patients who received mechanical ventilation due to COVID-19 and were discharged from hospital had a 96% survival rate at the two-year follow-up. There was no difference in overall recovery and quality of life between patients who did and did not require IMV, although respiratory morbidity remains high.

Continuous positive airway pressure and pronation outside the Intensive Care Unit in COVID-19 acute respiratory distress syndrome.

BACKGROUND: The efficacy and safety of continuous positive airway pressure and respiratory physiotherapy outside the Intensive Care Unit during a pandemic. METHODS: In this cohort study performed in February-May 2020 in a large teaching hospital in Milan, COVID-19 patients with adult respiratory distress syndrome receiving continuous positive airway pressure (positive end-expiratory pressure =10 cm H2O, FiO2=0.6, daily treatment duration: 4×3h-cycles) and respiratory physiotherapy including pronation outside the Intensive Care Unit were followed-up. RESULTS: Of 90 acute respiratory distress syndrome (ARDS) patients treated with continuous positive airway pressure (45/90, 50% pronated at least once) outside the Intensive Care Unit and with a median (interquartile) follow-up of 37 (11-46) days, 45 (50%) were discharged at home, 28 (31%) were still hospitalized, and 17 (19%) died. Continuous positive airway pressure failure was recorded for 35 (39%) patients. Patient mobilization was associated with reduced failure rates (P=0.033). No safety issues were observed. CONCLUSIONS: Continuous positive airway pressure with patient mobilization (including pronation) was effective and safe in patients with ARDS due to COVID-19 managed outside the Intensive Care Unit setting during the pandemic.

Outcomes of noninvasive ventilation as the ceiling of treatment in patients with COVID-19.

BACKGROUND: Non-invasive mechanical ventilation (NIV) is effective for symptom relief and respiratory support in patients with respiratory insufficiency, severe comorbidities and no indication to intubation. Experience with NIV as the ceiling of treatment in severely compromised novel coronavirus disease (COVID-19) patients is lacking. METHODS: We evaluated 159 patients with COVID-19-related acute respiratory syndrome (ARDS), 38 of whom with NIV as the ceiling of treatment, admitted to an ordinary ward and treated with continuous positive airway pressure (CPAP) and respiratory physiotherapy. Treatment failure and death were correlated with clinical and laboratory parameters in the whole cohort and in patients with NIV as the ceiling of treatment. RESULTS: Patients who had NIV as the ceiling of treatment were elderly, with a low BMI and a high burden of comorbidities, showed clinical and laboratory signs of multiorgan insufficiency on admission and of rapidly deteriorating vital signs during the first week of treatment. NIV failure occurred overall in 77 (48%) patients, and 27/38 patients with NIV as the ceiling of treatment died. Congestive heart failure, chronic benign hematological diseases and inability/refusal to receive respiratory physiotherapy were independently associated to NIV failure and mortality. Need for increased positive end-expiratory pressures and low platelets were associated with NIV failure. Death was associated to cerebrovascular disease, need for CPAP cycles longer than 12 h and, in the subgroup of patients with NIV as the ceiling of treatment, was heralded by vital sign deterioration within 48 h. CONCLUSIONS: NIV and physiotherapy are a viable treatment option for patients with severe COVID-19 and severe comorbidities.

Histopathological progression of hidradenitis suppurativa/acne inversa : A morphological study with a closer look on the early changes of the folliculosebaceous apocrine apparatus.

BACKGROUND: It is generally acknowledged that the first morphological change of hidradenitis suppurativa/acne inversa (HS/AI) consists of infundibular plugging of the folliculosebaceous apocrine apparatus, which is followed by acute and chronic inflammation, cysts with sinus formation, and fibrosis. Alternatively, it has been hypothesized that HS/AI is primarily a neutrophilic autoinflammatory disease and that the follicular plugging typical of this disease is secondary to inflammation. OBJECTIVE: To review the sequence of the changes that mark the disease development, we have performed a histopathologic study on the surgical material from a series of axillary and inguinal/perineal cases. METHODS: The histologic material from surgery on Hurley's second and third stage HS/AI was retrieved and collected with the patients' clinical images. The virtually uninvolved skin peripheral to the lesions was studied together with the main inflammatory foci on vertical sections stained with hematoxylin-eosin and immunohistochemistry for the follicle sheaths. RESULTS: The fully developed lesions showed acute and chronic, suppurative and granulomatous inflammation overlapping fibrosis, cysts, and sinuses. Instead, the skin adjacent to florid inflammation showed plugging and dysmorphic alterations of the hair follicles associated with immunopathological changes of the inner root sheath keratin expression. CONCLUSION: Our observations coincide with the classical pathological studies on the progressive changes of HS/AI; however, in our specimens, the virtually normal skin peripheral to the fully developed lesions show seemingly initial follicular changes that suggest development error. This finding would support the hypothesis of combined mutation-induced epithelial differentiative defects and immunological derangement in HS/AI pathogenesis.

Secukinumab efficacy in the treatment of nail psoriasis: a case series.

Nail involvement is frequent in patients with psoriasis, especially those with psoriatic arthritis (PsA), and can significantly impair quality of life (QoL). It is typically difficult to treat compared with skin lesions, although several conventional treatment options are available. The aim of this article is to describe our experience in the treatment of nail psoriasis with secukinumab in a case series. Fifteen patients (11 males and 4 females), with moderate-severe plaque psoriasis and nail psoriasis, eligible for systemic therapy, and received secukinumab. The Psoriasis Area and Severity Index (PASI) and body surface area (BSA) assessed cutaneous severity. Nail Psoriasis Severity Index (NAPSI) was used to evaluate nail involvement. Starting from 6 weeks after initiation of treatment with secukinumab 300 mg, a clinically significant response was observed, with progressive reduction of both skin and nail disease indexes. Average reduction of PASI was 75%, of BSA 70%, and of NAPSI 50%, at week 6. At week 12, NAPSI reduction was by 80%, of PASI 90%, and of BSA 97%. Effective treatment of both skin and nail psoriasis was obtained with secukinumab, a new approach to psoriatic patients resistant to topical therapy.

Plexiform Atypical Spitz Tumor With Rosette-Like Giant Cells: A Histologic and Immunohistochemical Study on a Case Suggesting Ganglioneuroblastic Differentiation: Review of the Literature and Considerations on Histogenesis.

Spitz nevi, atypical Spitz tumors and Spitzoid melanoma, the three clinicopathologic forms that constitute the spectrum of the Spitz-type melanocytic lesions, share a histologic picture characterized by large spindle and/or epithelioid ganglion-like cells, with various admixtures of multinucleate bizarre cells. This remarkable cytology has always been interpreted as an unusual, as well as unexplained form of atypia. We report a case of atypical Spitz tumor with Homer Wright-like rosettes, a feature characteristic of ganglioneuroblastic proliferation. Furthermore, the ganglion-like cells of the tumor showed basophilic punctuation in the cytoplasm, reminiscent of Nissl substance, and a few cells, whether spindled or epithelioid, were positive to neuron-specific enolase and glial fibrillary acid protein. Based on our findings, we hypothesize that the outstanding similarity of the ganglion-like cells of Spitz tumors to the normal parasympathetic ganglion cells and to the cells of ganglioneuroma and ganglioneuroblastoma may not be fortuitous. Instead, it may represent the expression of a specific pattern of melanocytic differentiation, analogous to the neurotization of common and cellular blue nevi, although in this case, it would privilege the parasympathetic lineage over the Schwannian, perineural, or endoneural pathway. Our hypothesis is supported by the literature reports of rosette formation and frank ganglioneuroblastic differentiation in Spitz tumors and melanoma and by the demonstration that parasympathetic neurons take origin from the same tracts of the neural crest as other neural and melanocytic cells.

A Case of Moderate Hidradenitis Suppurativa and Psoriasis Treated with Secukinumab

Hidradenitis suppurativa (HS) is a disorder of the apocrine gland causing a chronic, recurrent and painful inflammation. It is a disabilitating condition and, though many therapeutic options are available, the response is often ineffective in most cases and patients can present many recurrences with physical and psychological sequelae. Recent data had shown increased interleukin (IL)-17 serum levels in patients with HS. Psoriasis is a chronic immune-mediated inflammatory disorder and new evidences have shown the role of Th17 cells in its pathogenesis and the therapeutic efficacy of anti-IL-17 antibodies. We present a case of a patient suffering from psoriasis and HS successfully treated with anti-IL-17 antibodies for both conditions. This is the first case report of HS treated with secukinumab.

Postherpetic neuralgia, diabetic neuropathy, and trigeminal neuralgia - Chronic peripheral neuropathic pain in 58,480 rural Italian primary care patients.

INTRODUCTION: Chronic peripheral neuropathic pain (CPNP) is a condition due to peripheral nervous system diseases or injury, but its prevalence is unknown in Italian primary care. AIM: The aim of this study is to assess the prevalence of CPNP in a rural primary care area in Northern Italy. MATERIALS AND METHODS: A multicenter audit study was carried out in a rural area in Northern Italy with 113 participating general practitioners (GPs) seeing 58,480 patients >18 years during 3 months. Patients who for any reason attended GPs' surgeries and had symptoms suggestive of neuropathic pain (NP) were given the NP diagnostic questionnaire "Douleur Neuropathique en 4 Questions" (DN4) and recorded their pain level on a visual analog scale (VAS). RESULTS: Chronic NP was established by a DN4 score of ≥4 and a VAS pain score of ≥40 mm for >6 months together with a clinical diagnosis in 448 (254 women and 194 men) out of 58,480 patients giving a prevalence of 0.77%. 179 patients (0.31%) had diabetes neuropathy, 142 (0.24%) had postherpetic pain, 41 (0.07%) had trigeminal neuralgia, 27 (0.05%) had NP postinjury, 27 (0.05%) had NP caused by nerve entrapments, 11 (0.02%) had NP triggered by systemic diseases, and 21 (0.04%) had NP of unknown etiology. CONCLUSIONS: The prevalence of CPNP in this population of primary care attenders in a rural area in Northern Italy was 0.77%. Diabetes neuropathy (0.31%) and postherpetic pain (0.24%) were the two most common subgroups of NP, followed by trigeminal neuralgia (0.07%).

Vulvar cancer: a review for dermatologists.

Vulvar malignancies are important tumors of the female reproductive system. They represent a serious health issue with an incidence between 2 and 7 per 100,000 and year. We provide a review about most important cancer entities, i.e., melanoma, squamous cell carcinoma, basal cell carcinoma, neuroendocrine cancer, and skin adnexal malignancies.Squamous cell carcinoma is the most common vulvar malignancy that can develop from vulvar intraepithelial neoplasia or de novo. Basal cell carcinoma represents only 2% of all vulvar cancers. Melanoma of the vulva exists in two major types-superficial spreading and acral lentiginous. A special feature is the occurrence of multiple vulvar melanomas. Of the adnexal cancer types Paget's disease and carcinoma are seen more frequently than other adnexal malignancies. The dermatologist should be aware of this problem, since he might be the first to be consulted by patients for vulvar disease. Treatment should be interdisciplinary in close association to gynecologists, oncologists, and radiologists.

Avian mite dermatitis: an Italian case indicating the establishment and spread of Ornithonyssus bursa (Acari: Gamasida: Macronyssidae) (Berlese, 1888) in Europe.

BACKGROUND: Avian mite dermatitis is a skin disease caused in mammals by the incidental bites of blood-sucking mites which customarily parasitize wild and domestic birds. It manifests in the form of pruritic, erythematous, or urticarial papules, with a central sting mark, in skin regions normally covered by clothing. The species mainly implicated in human bite cases are Dermanyssus gallinae, Ornithonyssus sylviarum and, less frequently, Ornithonyssus bursa. The latter is mainly a tropical and subtropical mite and its - presumably transitory - presence has been recorded only once in Europe, in migratory birds. CASE REPORT: We report a case of avian mite dermatitis in a 70-year-old man, an owner of chickens, who lived in Sicily, an island in southern Italy. He presented with an itching, erythematous, papular eruption. Numerous mites were seen racing across his skin. The precise identification of O. bursa was based on the morphology of its plates and chelicerae and on the arrangement of its setae. CONCLUSIONS: Not only does this paper report the first European case of human infestation with O. bursa, it provides evidence that this alien species has settled and spread in the Old Continent. It may have been flown in from a small focus reported in Danish migratory birds in the 1980s or may have been accidentally introduced into Italy through the importation of infested poultry from South America. Such occurrences may have unpredictable epidemiological and ecological consequences. More comprehensive veterinary inspection of imported birds is desirable.

Environmental effects of storage preservation practices: controlled flushing of fine sediment from a small hydropower reservoir.

Sediment flushing may be effective in mitigating loss of reservoir storage due to siltation, but flushing must be controlled to limit the impact on the downstream environment. A reliable prediction of the environmental effects of sediment flushing is hindered by the limited scientific information currently available. Consequently, there may be some controversy as regards to management decisions, planning the work, and monitoring strategies. This paper summarizes the main results of a monitoring campaign on the stream below a small alpine hydropower reservoir subjected to annual flushing between 2006 and 2009. The removed sediment was essentially silt, and the suspended solid concentration (SSC) of the discharged water was controlled to alleviate downstream impact. Control was achieved through hydraulic regulation and mechanical digging, alternating daytime sediment evacuation, and nocturnal clear water release. The four operations lasted about two weeks each and had an average SSC of about 4 g L(-1). Maximum values of SSC were generally kept below 10 g L(-1). Downstream impact was quantified through sampling of fish fauna (brown trout) and macroinvertebrate in the final reach of the effluent stream. The benthic community was severely impaired by the flushing operations, but recovered to pre-flushing values in a few months. As expected, the impact on brown trout was heavier on juveniles. While data biasing due to fish removal and re-stocking cannot be ruled out, the fish community seems to have reached a state of equilibrium characterized by a lower density than was measured before the flushing operations.

Perineural pattern of aggregation of cellular blue nevus: probable histoarchitectural reminiscence of histogenesis.

A striking feature of cellular blue nevus consists in the presence, in its histologic picture, of numerous hypertrophic nerves and nerve-like figures, positive for histochemical and immunohistochemical methods for nerve fibers and myelin sheaths. These findings, first described in Masson's original article and repeatedly highlighted in the past for their possible histogenetic significance, are currently considered as merely coincidental. However, the thin conventional histologic sections, catching only short tracts of the nerves, preclude a correct observation of their route and do not allow us to verify if there is an architectural relationship between them and the nevus as a whole. With this aim, we observed a few specimens of cellular blue nevus on digitally overlapped images of contiguous 25-microm-thick sections, processed with Winkelmann's technique of silver impregnation for nerve fibers, which supplied an overall, 3-dimensional view of the lesions and the nerves running through them. In these images, the lobular form of the nevus could be seen gathering around a branching hypertrophic nerve, whose stem stretched vertically from the depth to the most superficial tract of the lesion. The nevus cell aggregates invested the stem and the limbs individually, and these followed the curvilinear contour of the nevus lobules. Our images represent evidence of a preferential perineural aggregation of cellular blue nevus, at least in its lobular form. This indicates that the numerous nerves and the neuroid figures, observed in detail-but within a limited perspective- in the conventional sections, are not merely coincidental and they could indeed be a sign of neural differentiation and/or a clue to the possible neural origin of the nevus.

Local reactions to tick bites.

A retrospective histological and immunohistochemical study has been carried out in 25 cases of tick bites recorded in our Departments. The samples that included an attached tick showed a cement cone anchoring the mouthparts to the skin and a blood-soaked, spongiform appearance of the superficial dermis, with a mild neutrophilic and eosinophilic infiltration. The vessels displayed a loose multilayered endothelial proliferation, with plump endothelia, permeated with erythrocytes. A few of them were severed, allowing copious blood extravasation. The established lesions included the following: erythema chronicum migrans-like cases, foreign body granulomas-sometimes containing remnants of the mouthparts-cutaneous lymphoid hyperplasia, either of the T-cell or the B-cell type, and tick-bite alopecia. In both the T-cell and B-cell pseudolymphomas, several vessels showed concentric endothelial and perithelial proliferation similar to that seen in the acute lesions. In the tick-bite alopecia, a lymphocytic infiltrate attacked the permanent portion of the hair follicles, whose reaction was a noticeable hyperplasia of the fibrous sheaths, although only a minority of the hairs was destroyed. The observed alterations are specific in the acute lesions and in the alopecia, where they directly arise as a result of the interactions between the host's tissues and the antihemostatic, anti-inflammatory, and immunomodulatory chemicals contained in the tick saliva. In the other lesions, the changes seem less characteristic, although the fragments of mouthparts and the special vascular changes provide a clue to their etiology.

Extramammary Paget Disease of the Axilla Associated With Comedo-like Apocrine Carcinoma In Situ.

Extramammary Paget disease of the axilla with underlying apocrine carcinoma has been reported only in six cases until now. This report deals with a seventh case characterized by the unique finding of comedo-like features evocative of large cell ductal breast carcinoma within an otherwise typical in situ apocrine carcinoma. This is characterized by spiral-shaped foci of epithelial proliferation with decapitation secretion and central masses of necrotic debris. A possible connection between the solid neoplasm and the overlying Paget disease is illustrated by a few apocrine-follicular units colonized by both the Paget cells and the structured adenocarcinoma. Here, although they display the same immunohistologic pattern of glandular differentiation, the two populations seem to be cytologically different and do not show signs of gradual transition to one another. Thus, they give the impression of parallel but distinct processes, which is consistent with the hypothesis of proliferative induction of a preexisting intraepidermal scattered population from the underlying adnexal carcinoma. The observed resemblance between apocrine carcinoma and comedo carcinoma of the breast, with its ontogenetic and phylogenetic implications, links not only the two neoplasms and the corresponding glands of origin but also mammary and extramammary Paget disease. This reinforces the unifying conception of Paget disease.