Modifications of lung microbiota structure in traumatic brain injury ventilated patients according to time and enteral feeding formulas: a prospective randomized study.

BACKGROUND: Specialized diets enriched with immune nutrients could be an important supplement in patients (pts) with acute traumatic brain injury (TBI). Omega-3 and arginine may interact with immune response and microbiota. No data are available about the role of the specialized diets in modulating the lung microbiota, and little is known about the influence of lung microbiota structure in development of ventilator-associated pneumonia (VAP) in TBI pts. The aims of this study are to evaluate the impact of specific nutrients on the lung microbiota and the variation of lung microbiota in TBI pts developing VAP. METHODS: A cohort of 31 TBI pts requiring mechanical ventilation in ICU was randomized for treatment with specialized (16pts) or standard nutrition (15pts). Alpha and beta diversity of lung microbiota were analyzed from bronco Alveolar Lavage (BAL) samples collected at admission and 7 days post-ICU admission in both groups. A further analysis was carried out on the same samples retrospectively grouped in VAP or no VAP pts. RESULTS: None developed VAP in the first week. Thereafter, ten out of thirty-one pts developed VAP. The BAL microbiota on VAP group showed significant differences in beta diversity and Staphylococcus and Acinetobacter Genera were high. The specialized nutrition had influence on beta diversity that reached statistical significance only in Bray-Curtis distance. CONCLUSION: Our data suggest that TBI patients who developed VAP during ICU stay have different structures of BAL microbiota either at admission and at 7 days post-ICU admission, while no correlation has been observed between different enteral formulas and microbiota composition in terms of richness and evenness. These findings suggest that targeting the lung microbiota may be a promising approach for preventing infections in critically ill patients.

Treatment of idiopathic pulmonary fibrosis: a position paper from a Nordic expert group.

Idiopathic pulmonary fibrosis (IPF) is a fatal progressive lung disease occurring in adults. In the last decade, the results of a number of clinical trials based on the updated disease classification have been published. The registration of pirfenidone and nintedanib, the first two pharmacological treatment options approved for IPF, marks a new chapter in the management of patients with this disease. Other nonpharmacological treatments such as lung transplantation, rehabilitation and palliation have also been shown to be beneficial for these patients. In this review, past and present management is discussed based on a comprehensive literature search. A treatment algorithm is presented based on available evidence and our overall clinical experience. In addition, unmet needs with regard to treatment are highlighted and discussed. We describe the development of various treatment options for IPF from the first consensus to recent guidelines based on evidence from large-scale, multinational, randomized clinical trials, which have led to registration of the first drugs for IPF.

Changes in Lipid Composition During Manganese-Induced Apoptosis in PC12 Cells.

Lipid composition of membranes is fundamental to modulate signaling pathways relying on lipid metabolites and/or membrane proteins, thus resulting in the regulation of important cell processes such as apoptosis. In this case, membrane remodeling is an early event important for the activation of signaling leading to cell death and removal of apoptotic cells. In the present study, we analyzed phospholipid, cholesterol and fatty acid content during apoptosis induced by manganese in PC12 cells. Lipid analysis of whole cells and detergent-resistant membranes was carried out by HPLC/GC. Results showed that apoptosis is associated with changes in lipid composition detectable in whole cell extracts, namely cholesterol, phosphatidylserine and phosphatidylethanolamine decreases. Noteworthy, phosphatidylserine level reduction was detectable before to the detection of apoptosis, in correlation with our previous study carried out by radioactive labelling. By contrast, phosphatidylserine and phosphatidylethanolamine changes were not detected in detergent resistant membranes, which instead showed an altered composition in phosphatidylinositol, phosphatidylcholine and sphingomyelin in apoptotic cells.

Regression in cutaneous melanoma: a comprehensive review from diagnosis to prognosis.

Histological regression in primary cutaneous melanoma occurs in 10-35% of cases. Although a large body of literature exists to suggest that histological regression serves very little purpose in predicting biologic behaviour with melanoma, recognizing the presence of regression at clinical and histological ground may still retain some value in grading melanoma aggressiveness. In the current review, a comprehensive overview of the main aspects of regression will be provided. Histologically, many classifications have been reported so far, but all of them only agreed on the presence of an infiltrate of lymphocytes admixed with pigment-laden macrophages underlying an atrophic epidermis with flattened rete ridges. Upon dermoscopy, regression is also named Blue White Scar-like areas and could be variably admixed with granularity or peppering. Almost fully regressed lesions represent a main diagnostic issue in dermoscopy, and thus, confocal microscopy can be of help to identify whether the tumour is melanocytic or not. The clinical utility of regression as a prognostic factor has been challenged recently. Nowadays, evidences showed that it is less likely associated to SLN metastases.

Morphological features of naevoid melanoma: results of a multicentre study of the International Dermoscopy Society.

BACKGROUND: Naevoid melanoma (NeM), a rare variant of melanoma, can be difficult to detect as its clinical and histopathological morphology can simulate a naevus. OBJECTIVES: To describe the clinical and dermoscopic features associated with NeM. METHODS: Lesions with a histopathological diagnosis of NeM were collected via an e-mail request sent to all members of the International Dermoscopy Society. All lesions were histopathologically reviewed and only lesions fulfilling a set of predefined histopathological criteria were included in the study and analysed for their clinical and dermoscopic features. RESULTS: Twenty-seven of 58 cases (47%) fulfilled the predefined histopathological criteria for NeM and were included in the study. Clinically, 16 of the 27 NeMs presented as a nodular lesion (59%), eight (30%) as plaque type and three (11%) as papular. Analysis of the global dermoscopic pattern identified three types of NeM. The first were naevus-like tumours (n = 13, 48%), typified by a papillomatous surface resembling a dermal naevus. In these lesions local dermoscopic features included irregular dots/globules (46%), multiple milia-like cysts (38%) and atypical vascular structures (46%). The second type were amelanotic tumours (n = 8, 30%), typified by an atypical vascular pattern (75%). The third type consisted of tumours displaying a multicomponent pattern (n = 4, 15%), characterized by classical local melanoma-specific criteria. Two lesions (7%) were classified as mixed-pattern tumours as they did not manifest any of the aforementioned patterns. CONCLUSIONS: While NeMs may be clinically difficult to differentiate from naevi, any papillomatous lesion displaying dermoscopically atypical vessels and/or irregular dots/globules should prompt consideration for the possible diagnosis of NeM.

Bleeding phenotype and correlation with factor XI (FXI) activity in congenital FXI deficiency: results of a retrospective study from a single centre.

Bleeding phenotype in factor XI (FXI)-deficient patients is variable, and not related to baseline FXI:Act. Aims of our study were to describe the characteristics and the management of surgery and deliveries in FXI-deficient patients, and to investigate the relationship between the haemorrhagic phenotype and the baseline FXI:Act. Ninety-five patients were diagnosed and followed in our centre for a median follow-up of 0.9 years (0.1-36.2); median FXI:Act of all patients: 38% (0.5-69%). Fifty-six patients (59%) experienced bleeding episodes not surgery-related. Prior to diagnosis, 64 patients underwent 132 surgeries, and after diagnosis, 23 patients underwent 36 surgeries. Globally 26 of 168 surgeries were prophylactically treated, whereas 142 of 168 were not. As regard as surgeries performed without prophylaxis, 30 bleeding events (21%) occurred in 21 patients. At diagnosis, the median FXI:Act of bleeding and non-bleeding patients was 28% and 37%, respectively, without statistically significant difference between the two groups (P = 0.26). As regard as surgeries performed under prophylactic treatment just 1 bleeding event occurred. Prior to diagnosis, 31 spontaneous deliveries (SD) and eight caesarian sections (CS) were performed without prophylaxis: 4 postpartum haemorrhages (10.5%) occurred (patients FXI:Act: 2%, 6%, 27%, 52.3% respectively). After diagnosis, four SD and five CS were performed with prophylaxis: no postpartum haemorrhages occurred. We confirm the wide bleeding phenotype variability in FXI-deficient patients, not related to the baseline FXI:Act levels. We highlight the importance of performing a correct diagnosis and follow-up, because a good management of prophylactic treatment, dramatically reduces the bleeding rate in case of surgery or deliveries.

A specific DNA methylation profile correlates with a high risk of disease progression in stage I classical (Alibert-Bazin type) mycosis fungoides.

BACKGROUND: Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma; in its classical presentation it evolves slowly, but it can have an aggressive course in a subset of patients. OBJECTIVES: To investigate the impact of epigenetic mechanisms on the progression of early stage MF. METHODS: We analysed DNA methylation at 12 different loci and long interspersed nucleotide elements-1 (LINE-1), as a surrogate marker of global methylation, on tissue samples from 41 patients with stage I MF followed up for at least 12 years or until disease progression. The methylation profiles were also analysed in two T-cell lymphoma cell lines and correlated with gene expression. RESULTS: The selected loci were methylated in a tumour-specific manner; concomitant hypermethylation of at least four loci was more frequent in cases progressing within 1-3 and 3-6 years than in late-progressive or non-progressive cases. LINE-1 methylation was significantly lower in rapidly progressive MF at 3 years (61%, P < 0·001) than in those at 12 years (67%). PPARG, SOCS1 and NEUROG1 methylation showed remarkable differences among the prognostic groups, but only PPARG was a significant predictor of disease progression within 6 years, after adjustment for patients' age or gender. Strikingly, a methylation profile similar to progressive cases was found in highly proliferative Sézary-derived HUT78 cells but not in MF-derived HUT102 cells. Exposure to a DNA demethylating agent restored sensitivity to apoptosis and cell cycle arrest. CONCLUSIONS: Epigenetic silencing of specific biomarkers can predict the risk of disease progression in early-stage MF, providing insights into its pathogenesis, prognosis and therapy.

Dermoscopy uncovers clinically undetectable pigmentation in basal cell carcinoma.

BACKGROUND: The presence of pigmentation might influence the management of basal cell carcinoma (BCC), with pigmented BCC responding poorly to certain treatments. Clinical studies report on a generally lower frequency of pigmentation compared with dermoscopic and histopathological studies, but the true frequency at which pigmentation occurs in clinically nonpigmented BCC has not been studied in detail. OBJECTIVES: To compare the clinical and dermoscopic frequency of pigmentation in a series of histopathologically diagnosed BCCs and to correlate it with patient demographics, tumour location and histopathological subtype. METHODS: Clinical and dermoscopic images of histopathologically confirmed BCCs were retrospectively evaluated for the presence of pigmentation. Dichotomous outcome variables were clinically pigmented and dermoscopically pigmented BCC. All separate dermoscopic variables were included in the analysis. Differences in proportions were evaluated using Pearson's chi-square test. RESULTS: Five hundred and seven BCCs from 507 patients with a mean age of 67 years and a male-to-female ratio of 1.35 : 1 were included in the study. Clinically, 295 tumours were judged as nonpigmented. Of those, dermoscopy disclosed pigmentation in 88 cases (29.8%). Overall, blue-grey ovoid nests were the most frequent dermoscopic pattern (n = 184, 36.3%), followed by multiple blue-grey dots/globules (n = 147, 29%) and maple-leaf-like areas (n = 70, 13.8%). Superficial tumours exhibited mainly maple-leaf-like areas, spoke-wheel areas and brown dots, whereas pigmented nodular BCC was most frequently typified by the presence of blue-grey ovoid nests. CONCLUSIONS: Dermoscopy allows detection of pigmentation in about 30% of clinically nonpigmented BCCs, providing additional information that may aid the clinical choice of adequate treatment modalities.

Serological and molecular survey of Q fever in the dog population of the Campania region, southern Italy.

Q fever is a re-emerging zoonosis whose epidemiological cycle in ruminants is well defined, while the role of other species (including pets) is still debated. In this study, the serological and molecular prevalence of Coxiella burnetii in a sample of dogs in the Campania region, southern Italy was evaluated. A seroprevalence of 5.97 % (16/268) was observed using a commercial multispecies ELISA, compared to only 2.7 % (5/197) at the molecular level. No risk factors correlated with higher levels of exposure except for the size of the animal (small dogs showed significantly higher seroprevalence). Positive samples were further evaluated for reactivity to phase I and II antigens using IFA and phase-specific ELISAs (for specific IgG detection). Two animals showed antibodies against both phases of infection, suggesting that Coxiella burnetii seroconversion in dogs follows similar dynamics to those observed in ruminants. One of the five samples that showed positive results in real-time PCR was confirmed at the PCR endpoint and showed similarity with other Coxiella spp. strains detected in tick and dog samples when sequenced. In this study, we demonstrated exposure to Coxiella burnetii for different categories of dogs in southern Italy, including pet dogs living indoors. Since reports of transmission of infection from pets to humans have been described in both rural and urban areas, careful surveillance of these species is also necessary. In the lack of additional information, comprehending the risk to humans requires monitoring of wild and domestic animal populations.

Detection of anti-HEV antibodies but no molecular positivity in dogs in the Campania region, southern Italy.

Paslahepevirus balayani genotypes 3 and 4 (HEV-3 and 4) have zoonotic potential and can be transmitted to humans and animals through the consumption of contaminated raw or undercooked meat. Although it has been demonstrated that dogs are susceptible to the infection and produce specific antibodies, the epidemiological role of this species is not yet well defined. This study aimed to evaluate the circulation of HEV at the serological and molecular level in the dog population of the Campania region, southern Italy. A total of 231 dogs were sampled, divided according to several variables (sex, age, origin, lifestyle, location, size, and breed), and tested for the presence of HEV antibodies using a commercial multi-species ELISA. A total of 197 blood samples and 170 stool samples were tested with two specific PCRs in order to detect viral RNA. A total of 19 out samples of 231 were seropositive, obtaining an exposure (8.2%) similar to that observed in other European countries. The univariate and multivariate analysis revealed a wide exposure to stray dogs and animals from the province of Salerno. All samples tested with molecular methods were negative. Defining the role of domestic carnivores continues to be a "one health" challenge, although it appears that they do not eliminate the virus and therefore do not pose a danger to humans. In the absence of other evidence, it is advisable to continue to carry out surveillance also for domestic animals, which, due to ethological characteristics or their position in the food chain, could be predisposed to being exposed to HEV.

Dermoscopy of basosquamous carcinoma.

BACKGROUND: Basosquamous carcinoma (BSC) is a rare and potentially aggressive tumour, characterized by clinical and pathological features of both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). It is reported to have a nonspecific clinical presentation, which makes naked-eye diagnosis a challenge. OBJECTIVES: To describe the dermoscopic patterns of BSC, which may facilitate early diagnosis and accurate management. METHODS: This was a retrospective evaluation of clinical and dermoscopic images of histopathologically proven BSC, collected from skin cancer centres in Australia (Perth), Greece (Thessaloniki) and Italy (Naples, Reggio Emilia). RESULTS: Twenty-two tumours were included in the study. Our analysis revealed that the dermoscopic pattern of BSC comprises BCC-related criteria, as well as features that are known to characterize invasive SCC. The most frequently detected criteria were: unfocused (peripheral) arborizing vessels (73%), keratin masses (73%), white structureless areas (73%), superficial scale (68%), ulceration or blood crusts (68%), white structures (64%), blue-grey blotches (59%) and blood spots in keratin masses (55%). Notably, all but one of the tumours exhibited at least one BCC-related plus one SCC-related dermoscopic feature. CONCLUSIONS: BSC appears to have overlapping dermoscopic features of BCC and invasive SCC, and detection of at least one dermoscopic criterion of both BCC and SCC should raise suspicion for the tumour. Appreciation of the dermoscopic patterns of BSC might assist in the timely and accurate diagnosis and subsequent optimal management of this unusual and potentially metastatic skin tumour.

Small-diameter melanocytic lesions: morphological analysis by means of in vivo confocal microscopy.

BACKGROUND: Small-diameter melanocytic lesions represent a diagnostic challenge for clinicians, as they do not follow the ABCD rule for diagnosis and do not always display reliable histopathological criteria. OBJECTIVES: To analyse the confocal features of small-diameter lesions (naevi and melanomas with diameter ≤ 5 mm) to determine whether they show specific morphological criteria. METHODS: Twenty-four melanomas and 72 naevi were subjected to dermoscopic and confocal evaluation along with histopathology. Significant dermoscopic and confocal differences between melanomas and naevi were evaluated by means of the Pearson χ(2) test. Odds ratios and 95% confidence intervals were calculated for each parameter. Binary logistic regression was performed to identify the reflectance confocal microscopy (RCM) independently significant features for melanoma diagnosis. RESULTS: The seven-point checklist dermoscopic score was ≥ 3 in 22 melanomas and in 33 naevi. The combination of cells' pleomorphism and architectural disorder (i.e. nonspecific pattern or irregular junctional nests upon confocal examination) are the most striking criteria for consistent diagnosis of small melanoma. The presence of atypical cells, more than five atypical cells per mm(2) , and roundish atypical cells at the dermoepidermal junction showed the highest odds ratios. From logistic regression, the presence of at least five pagetoid cells per mm(2) , tangled lines within the epidermis, and atypical roundish cells at the dermoepidermal junction resulted in the three independent confocal parameters that characterized small melanomas. CONCLUSIONS: Small melanomas frequently reveal specific dermoscopic and confocal features. Moreover, the combination of dermoscopy and RCM can lead to a correct diagnosis of a number of naevi that share some morphological aspects with melanomas.

Obstetric outcomes in women who sustained a spinal cord injury during pregnancy.

STUDY DESIGN: Case report. SETTING: Prince of Wales Spinal Cord Injuries Unit, Sydney, Australia. METHODS: Interrogation of our unit database identified only two women who became spinal cord injured while pregnant; their medical records were reviewed and an unstructured follow-up telephone interview conducted 6 years after discharge. Case 1: CC sustained a fracture dislocation with paraplegia at the sixth thoracic level (T6) in a motorbike accident while she was pregnant, 12-week gestational age (GA). Profound shock and hypoxia complicated the injury and recurrent urinary tract infections complicated the rest of her pregnancy. A baby with arthrogryposis multiplex congenita was delivered at full term. Severe cerebral palsy (CP) and deafness were present at follow-up 6 years later. Case 2: A 33-year-old multigravida, 27 weeks GA, developed sudden, spontaneous onset of paraplegia (T3 ASIA B) due to an extradural haematoma, which was evacuated on the day of admission. Systolic blood pressure was maintained above 90 mm Hg during and after surgery. A normal, healthy boy was delivered by caesarean section at 40 weeks GA and remained so at 6 years. CONCLUSION: Traumatic spinal cord injury (SCI) with its attendant multiple potential insults to the developing foetus results in a high risk of foetal loss and malformation particularly in the first trimester. However, if the injury occurs later in pregnancy and if blood pressure and oxygenation are maintained, the risk of foetal loss and abnormality may be substantially reduced.

Treating telangiectasias: my method.

AIM: The authors propose a new classification of telangiectasias: conditions involving demonstrated reflux are classified as type A telangiectasias; clustered, spider telangiectasias not related to reflux and with vein diameters of >0.2 mm are classified as type B, while isolated telangiectatic veins of ≤0.2 mm diameter are classed as type C. This histological and pathophysiological approach is the basis for the Authors' Multi-Therapy Treatment Protocol (MTT). METHODS: The treatment regimen provides for initial treatment of type A telangiectasias with just conventional reflux sclerotherapy, followed three weeks later by treatment of type B telangiectasias with 0.25-0.5% polidocanol foam, associated with both external compression and tumescent vasoconstriction (START technique). This is then followed after a further three months by dermal stimulation with mesoglycan (LIDS technique) to reinforce the district underlying the type C telangiectasias. The MTT Protocol was used on 63 patients (125 limbs). A 12-month follow-up showed the treatment regimen to provide better aesthetic and functional results than classical sclerotherapy, with few adverse effects and greater patient satisfaction.

Severe pneumonia after intravesical BCG instillation in a patient with invasive bladder cancer: case report and literature review.

We present here the case of a 66 year old man with a severe bilateral community acquired pneumonia secondary to dissemination after an intravesical instillation of bacilllus Calmette-Guerin (BCG). Diagnosis was based on positive polymerase chain reaction (PCR) for mycobacterium tuberculosis complex in bronchoalveolar lavage and on the finding on transbronchial biopsy of non necrotising granulomas histopathologically similar to the granulomas found in bladder biopsies. These findings were confirmed using a validated real time PCR assay demonstrating the presence of the BCG genome in transbronchial and bladder biopsies.

Panniculitis with vasculitis.

Panniculitides encompass a great number of different entities; however, once a vasculitis has been detected histopathologically within the subcutaneous tissue, the differential diagnosis is mainly restricted to polyarteritis (panarteritis) nodosa (PAN), nodular vasculitis (NV), and Bazin's erythema induratum (EI). Patients with PAN may have the disease confined to the skin, but must be followed over a long period because many of them develop late systemic disease. The NV/EI group represents by far the most common type of lobular panniculitis with vasculitis; we prefer keeping the distinction between the two entities by underlining the equation NV positive tuberculin skin test = EI. Other lobular panniculitides with vasculitis are exceedingly rare and set in a systemic background which can be infectious (lepromatous leprosy panniculitides) or autoimmune/dysreactive (neutrophilic lobular panniculitis in rheumatoid arthritis, lobular panniculitis in inflammatory bowel disease).