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Background: Nodular lesions have common clinical appearance but different prognoses. Differential diagnosis between melanoma (MM), basal cell carcinoma (BCC) and dermal naevus (DN) poses a challenge in clinical practice. Reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) are promising non‐invasive imaging techniques, potentially able to decrease redundant biopsies. RCM allows in vivo visualization of skin down to the papillary dermis at almost histological resolution, while OCT, particularly dynamic OCT (D‐OCT), provides images deeper within the dermis and reveals the vascular pattern. Objectives: To identify correlating features observed with RCM and OCT associated with the different nodular lesion diagnoses. Methods: We retrospectively assessed 68 nodular lesions (30 MM, 20 BCC and 18 DN) with RCM and subsequently OCT. At the end of the study, evaluations were matched with histopathological diagnosis and statistical analysis was performed. Results: In MM, 57% (17/30) evidenced both cerebriform nests at RCM and icicle‐shaped structures at OCT, with higher average Breslow index. In 80% of BCCs with basaloid islands at RCM, OCT showed ovoid structures. More than half of DN (56%) showed hyporeflective nests at OCT and either dense nests or dense and sparse nests at RCM. Conclusions: The combined use of RCM and OCT offers a better understanding of the morphological architecture of nodular lesions, correlating RCM parameters with OCT and vice versa, assisting in turn with early differential diagnosis of malignant and benign nodular lesions. The correlation between icicle‐shaped structures and cerebriform nests in MM and their association with Breslow index requires future research. [ABSTRACT FROM AUTHOR]

Extramammary Paget's disease (EMPD) is a rare, slow-growing cancer related to Paget's disease of the breast or mammary Paget's disease (MPD). Optical coherence tomography imaging of the scrotum demonstrated an irregular surface with generalized enhancement. [Extracted from the article]

Basal cell carcinoma (BCC) is the most frequent form of skin cancer. Patient characteristics, including patient demographics, initial diagnosis and BCC anatomical location. [Extracted from the article]

Introduction: Lichen sclerosus (LS) is a chronic inflammatory dermatosis predominantly affecting the anogenital area, with potential systemic implications., Objective: Our aim was to elucidate its clinical characteristics and management strategies., Methods: We conducted a retrospective observational study on adult patients with LS referred to our center between January 2022 and December 2023., Results: Forty-six adult subjects affected with LS were enrolled in the present study. The majority of patients presented with genital involvement, but a significant subset also exhibited extragenital LS and concomitant immune-mediated disorders. Common symptoms included itching, soreness, and dyspareunia, with characteristic skin findings of erythema and atrophy. Topical corticosteroids were the mainstay of therapy, complemented by alternative treatments in refractory cases. Alternative therapeutic approaches, such as PRP (platelet rich plasma) or ADSC (adipose-tissue derived stromal/stem cell)-based strategies, were effectively employed in refractory cases, in the absence of major adverse events., Conclusions: Our findings underscore the importance of alternative approaches in the management of LS and highlight the need for further research to elucidate its pathogenesis and optimize therapeutic interventions.

Acellular dermal matrices currently represent a useful reconstructive method in onco-dermatologic surgery. Nevertheless, they have some limitations, especially in terms of costs and outpatient post-operative wound care. While some studies on their cost-to-benefit ratio in breast surgery have already been issued, evidence is currently lacking in onco-dermatological surgery. The aim of this study was to evaluate the clinical outcomes perceived by patients who had undergone onco-dermatologic surgery in which either acellular dermal matrices or skin grafts had been used as reconstructive methods. A study population of 150 patients was identified retrospectively and patients' degree of satisfaction was assessed through the Global Aesthetic Improvement Scale and the Patient Scar Scale Questionnaire. Despite similar scores among the study groups, slightly better results were appreciable after single-stage grafting. However, to what extent these variations really represent a significant difference from a clinical point of view remains to be determined. Moreover, other potential bias in the interpretation of our results may reside in differences in terms of age, body location and baseline tumor size among the study groups. Therefore, further research is needed., Competing Interests: Conflict of interest: the authors declare no potential conflict of interest., (Copyright © 2024, the Author(s).)

The relation between glucose homeostasis and cerebral blood flow (CBF) and their correlation to outcome in neonatal hypoxic-ischemic encephalopathy are unclear. In this short communication, we tried to determine whether changes in regional oxygen saturation (rSO2), as measured by near-infrared spectroscopy (NIRS), in asphyxiated neonates during therapeutic hypothermia correlate with the glycemic profile and whether NIRS and continuous glucose monitoring are useful in identifying cooled asphyxiated neonates at high risk of brain injury. Although there was no correlation between blood glucose and CBF in this small cohort of asphyxiated neonates (13 neonates admitted to the IRCCS Giannina Gaslini NICU in Genoa between March and September 2021), after 24 h of life, increased rSO 2 and glucose variability with a tendency toward hyperglycemia distinguished neonates who subsequently acquired brain injury from those who did not. As a result of this, it may be possible to monitor cerebral perfusion and metabolic changes as soon as possible after delivery in order to prevent poorer outcomes., Competing Interests: No competing financial interests exist., (© Giulia Vagelli et al., 2024; Published by Mary Ann Liebert, Inc.)

In this experimental study the autofluorescence of squamous carcinoma cells, stimulated by 6 different excitation wavelengths in the range 280-533 nm, has been compared with the autofluorescence of normal control keratinocytes. Skin cells were cultivated in vitro, to isolate their characteristic autofluorescence form the more complex one that would be originated by the complete skin tissue. Autofluorescence spectra in the visible range were complemented by absorption measurements. It was observed that the control cells showed characteristic emission (and absorption) structures due to typical endogenous chromophores [FAD and NAD(P)H, lipo-pigments, porphyrins], that were severely dumped in pathological cells. The autofluorescence spectra were then elaborated by multivariate analysis: after a first exploratory data analysis by means of Principal Component Analysis, the whole dataset was used to develop classification models using partial least squares-discriminant analysis, to differentiate between normal and pathological cells. This permitted us to identify the most suitable fluorescence spectral interval, in the 550-670 nm range, to discriminate between normal and pathological behavior, independently on the excitation wavelength., (© 2023 The Authors. Journal of Biophotonics published by Wiley-VCH GmbH.)

Background: MatriDerm and Integra are both widely used collagenic acellular dermal matrices (ADMs) in the surgical setting, with similar characteristics in terms of healing time and clinical indication. The aim of the present study is to compare the two ADMs in terms of clinical and histological results in the setting of dermato-oncological surgery., Methods: Ten consecutive patients with medical indications to undergo surgical excision of skin cancers were treated with a 2-step procedure at our Dermatologic Surgery Unit. Immediately after tumor removal, both ADMs were positioned on the wound bed, one adjacent to the other. Closure through split-thickness skin grafting was performed after approximately 3 weeks. Conventional histology, immunostaining and ELISA assay were performed on cutaneous samples at different timepoints., Results: No significant differences were detected in terms of either final clinical outcomes or in extracellular matrix content of the neoformed dermis. However, Matriderm was observed to induce scar retraction more frequently. In contrast, Integra was shown to carry higher infectious risk and to be more slowly reabsorbed into the wound bed. Sometimes foreign body-like granulomatous reactions were also observed, especially in Integra samples., Conclusions: Even in the presence of subtle differences between the ADMs, comparable global outcomes were demonstrated after dermato-oncological surgery.

Background: Hereditary epidermolysis bullosa (EB) is a rare genodermatosis characterized by skin fragility and blistering of the skin and mucous membranes in reaction to minimal traumas. The development of cutaneous squamous cell carcinomas (cSCCs) is one of the most common medical complications in junctional and dystrophic forms of the disease. Complete surgical excision of cutaneous tumors represents the gold standard of treatment. However, not only recognition of cSCCs can be challenging in the affected skin but also wound closure after surgical excision poses a great therapeutic challenge in EB patients. The aim of our study was to analyze the postoperative outcomes of such patients in order to have a better knowledge of the main critical issues in their surgical management and oncological follow-up., Methods: We retrospectively identified a cohort of five EB patients treated at Modena University Hospital. Collected data included patient age and sex, date of cSCC diagnosis, relapses/recurrences, site of the neoplasm, number of surgical interventions, use of dermal substitutes, and postoperative infections., Results: A total of 26 cSCCs were detected in our cohort. Forty-one surgical interventions were necessary to achieve excision of cSCCs with clear margins, varying from 1 to 4 surgical sessions per cSCC. Dermal substitutes were used in most cases but carried a higher infectious risk., Conclusions: EB patients tend to develop numerous cSCCs that often relapse even after complete excision with clear margins. These results stress the importance of early cSCC diagnosis and strict postsurgical follow-up., (© 2022 The Authors. International Journal of Dermatology published by Wiley Periodicals LLC on behalf of the International Society of Dermatology.)

Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive disease associated with a highly variable clinical presentation, including systemic vasculitis, immunodeficiency, and cytopenia. We report a case of a 16-year-old girl affected by recurrent viral infections [including cytomegalovirus (CMV)-related hepatitis and measles vaccine virus-associated manifestations] and persistent inflammation, which occurred after Parvovirus infection and complicated by secondary hemophagocytic lymphohistiocytosis (HLH). HLH's first episode presented at 6 years of age and was preceded by persistent fever and arthralgia with evidence of Parvovirus B19 infection. The episode responded to intravenous steroids but relapsed during steroids tapering. High-dose intravenous immunoglobulin (IVIG) helped manage her clinical symptoms and systemic inflammation. The frequency of IVIG administration and the dosage were progressively reduced. At the age of 9, she experienced varicella zoster virus (VZV) reactivation followed by the recurrence of the inflammatory phenotype complicated by HLH with neurological involvement. Again, high-dose steroids and monthly IVIG resulted in a quick response. Targeted next-generation sequencing (NGS) for autoinflammatory diseases and immunodeficiencies revealed the homozygous Leu183Pro ADA2 mutation, which was confirmed by Sanger analysis. ADA2 enzymatic test showed a complete loss of ADA2 activity. For about 3 years, IVIG alone was completely effective in preventing flares of inflammation and neurological manifestations. Anti-TNF treatment was started at the age of 13 for the appearance of recurrent genital ulcers, with a complete response. This case further expands the clinical spectrum of DADA2 and emphasizes the importance of extensive genetic testing in clinical phenotypes characterized by persistent unspecific inflammatory syndromes. The use of high doses of IVIG might represent a possible effective immune modulator, especially in combination with anti-TNF treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Drago, Garbarino, Signa, Grossi, Schena, Penco, Santori, Candotti, Boztug, Volpi, Gattorno and Caorsi.)

Non-melanoma skin cancer (NMSC) is the most common malignant tumor affecting fair-skinned people. Increasing incidence rates of NMSC have been reported worldwide, which is an important challenge in terms of public health management. Surgical excision with pre-operatively identified margins is one of the most common and effective treatment strategies. Incomplete tumor removal is associated with a very high risk of recurrence and re-excision. Biological tissues can absorb and re-emit specific light wave-lengths, detectable through spectrophotometric devices. Such a phenomenon is known as autofluorescence (AF). AF spectroscopy has been widely explored for non-invasive, early detection of NMSC as well as for evaluation of surgical margins before excision. Fluorescence-aided diagnosis is based on differences in spectral characteristics between healthy and neoplastic skin. Understanding the biological basis of such differences and correlating AF intensity to histological features could improve the diagnostic accuracy of skin fluorescence spectroscopy. The primary objective of the present pre-clinical ex vivo study is to investigate the correlation between the intensity of cutaneous AF and the histopathological features of NMSC. Ninety-eight lesions suggestive for NMSCs were radically excised from 75 patients (46 M; 29 F; mean age: 79 years). After removal, 115 specific reference points on lesions ("cases"; 59 on BBC, 53 on SCC and 3 on other lesions) and on peri-lesional healthy skin (controls; 115 healthy skin) were identified and marked through suture stitches. Such reference points were irradiated at 400-430 nm wavelength, and resulting emission AF spectra were acquired through spectrophotometry. For each case, AFIR (autofluorescence intensity ratio) was measured as the ratio between the number of photons emitted at a wavelength ranging between 450 and 700 nm (peak: 500 nm) in the healthy skin and that was captured in the pathological tissue. At the histological level, hyperkeratosis, neoangiogenesis, cellular atypia, epithelial thickening, fibrosis and elastosis were quantified by light microscopy and were assessed through a previously validated grading system. Statistical correlation between histologic variables and AFIR was calculated through linear regression. Spectrometric evaluation was performed on 230 (115 cases + 115 controls) reference points. The mean AFIR for BCC group was 4.5, while the mean AFIR for SCC group was 4.4 and the fluorescence peaks at 500 nm were approximately 4 times lower (hypo-fluorescent) in BCCs and in SCCs than in healthy skin. Histological variables significantly associated with alteration of AFIR were fibrosis and elastosis ( p < 0.05), neoangiogenesis, hyperkeratosis and epithelial thickening. Cellular atypia was not significantly associated with alteration of AFIR. The intensity of fluorescence emission in neoplastic tissues was approximately 4 times lower than that in healthy tissues. Histopathological features such as hyperkeratosis, neoangiogenesis, fibrosis and elastosis are statistically associated with the decrease in AFIR. We hypothesize that such tissue alterations are among the possible biophysical and biochemical bases of difference in emission AF between neoplastic and healthy tissue. The results of the present evaluation highlighted the possible usefulness of autofluorescence as diagnostic, non-invasive and real-time tool for NMSCs.

Background: Metastasis from cutaneous squamous cell carcinoma (cSCC) mainly involve the regional nodal basin, with an incidence ranging from 2-4% until 15% in case of high-risk tumors. When dealing with high-risk cSCC, ultrasound examination is recommended every 3-4 months during follow-up. We aimed to determine the role of US examination in the early diagnosis of nodal metastasis from cSCC., Methods: We conducted a retrospective cohort study enrolling consecutive cases of histopathologically verified cSCCs from January 2007 to March 2018. All the enrolled cases were followed for at least one year and all cases of histopathologically verified metastasis were registered. We also reported if ultrasound of the regional basin was performed between the primary diagnosis and metastasis and how the latter was identified, through ultrasounds or clinically. A Kaplan-Meier survival analysis was conducted on patients undergoing ultrasounds during follow-up., Results: A total of 1881 cases, belonging to 1441 patients were included. Thirty-one cases of nodal metastasis diagnosed after the primary tumor, in as many patients, were identified. All of the selected metastasis derived from high-risk primary cSCCs. Only in 19 cases ultrasound examination was performed during follow-up; of these, 10 were diagnosed through ultrasounds and 9 clinically. Survival analysis demonstrated that the time interval between primary tumor and metastasis was significantly lower for patients with metastasis diagnosed by ultrasounds than clinically (P=0.036)., Conclusions: Our study highlighted the need to optimize the use of nodal ultrasound examination for high-risk cSCCs in order to early detect metastasis.

Evaluation and understanding the effect of drug delivery in in vitro systems is fundamental in drug discovery. We present an assay based on real-time electrical impedance spectroscopy (EIS) measurements that can be used to follow the internalisation and cytotoxic effect of a matrix metalloproteinase (MMP)-sensitive liposome formulation loaded with oxaliplatin (OxPt) on colorectal cancer cells. The EIS response identified two different cellular processes: (i) a negative peak in the cell index (CI) within the first 5 h, due to onset of liposome endocytosis, followed by (ii) a subsequent CI increase, due to the reattachment of cells until the onset of cytotoxicity with a decrease in CI. Free OxPt or OxPt-loaded Stealth liposomes did not show this two-stage EIS response; the latter can be due to the fact that Stealth cannot be cleaved by MMPs and thus is not taken up by the cells. Real-time bright-field imaging supported the EIS data, showing variations in cell adherence and cell morphology after exposure to the different liposome formulations. A drastic decrease in cell coverage as well as rounding up of cells during the first 5 h of exposure to OxPt-loaded (MMP)-sensitive liposome formulation is reflected by the first negative EIS response, which indicates the onset of liposome endocytosis. Graphical abstract.

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory disorder. Several medical treatments, with varying degrees of efficacy, have been developed. However, in most cases of advanced HS, the definitive treatment option is often represented by surgical excisions., Objective: Surgical techniques, reconstructive approach, and local wound care should be accurately designed in order to obtain the best result. In this review we analyze the possible surgical treatments and local wound care., Methods: A MEDLINE search was performed on the various surgical treatments, reconstructive techniques, and local wound care., Results: Surgical treatment is a common therapeutic modality for HS. Different surgical reconstructive techniques and post-surgical wound care approaches are described for the management of HS patients., Conclusions: There were few high-quality evidence-based studies evaluating the surgical management of HS. Many disparate HS severity scores were used in these studies, making comparisons between them difficult. Nonetheless, research on different surgical approaches and wound care management has increased substantially in the past decade and it has given patients more surgical therapeutic strategies. The description of the best combinations and timing of surgery, wound care, and medical therapies will be a matter of future research for the definition of the optimal management of the HS patient., Competing Interests: The authors have no conflict of interests to declare., (Copyright © 2020 by S. Karger AG, Basel.)

Hidradenitis suppurativa (HS) is a chronic inflammatory disorder. Several medical treatments, with varying degree of efficacy, have been developed. However, in most cases of advanced (HS), the definitive treatment option is often represented by surgical excisions. Surgical techniques, reconstructive approach, and local wound care should be accurately designed in order to obtain the best result. In this letter, we analyzed the possible surgical treatments and local wound care. A literature review was performed on the various surgical treatments, reconstructive techniques, and local wound care. Surgical treatment is a common therapeutic modality for HS. Different surgical reconstructive techniques and postsurgical wound care approaches are described for the management of HS patients. There were few high-quality evidence-based studies evaluating the surgical management of HS. Many disparate HS severity scores were used in these studies making comparison between them difficult. Nonetheless, research into different surgical approaches and wound care management has increased substantially in the past decade and has given patients more surgical therapeutic strategies. The description of the best combinations and timing of surgery, wound care and medical therapies, will be a matter of future research for the definition of the optimal management of HS patient., (© 2020 Wiley Periodicals LLC.)

Detection of a single base mutation in Mycobacterium tuberculosis DNA can provide fast and highly specific diagnosis of antibiotic-resistant tuberculosis. Mutation-specific ligation of padlock probes (PLPs) on the target followed by rolling circle amplification (RCA) is highly specific, but challenging to integrate in a simple microfluidic device due to the low temperature stability of the phi29 polymerase and the interference of phi29 with the PLP annealing and ligation. Here, we utilized the higher operation temperature and temperature stability of Equiphi29 polymerase to simplify the integration of the PLP ligation and RCA steps of an RCA assay in two different strategies performed at uniform temperature. In strategy I, PLP annealing took place off-chip and the PLP ligation and RCA were performed in one pot and the two reactions were clocked by a change of the temperature. For a total assay time of about 1.5 h, we obtained a limit of detection of 2 pM. In strategy II, the DNA ligation mixture and the RCA mixture were separated into two chambers on a microfluidic disc. After on-disc PLP annealing and ligation, the disc was spun to mix reagents and initiate RCA. For a total assay time of about 2 h, we obtained a limit of detection of 5 pM. Graphical abstract.

Rolling circle amplification (RCA) of a synthetic nucleic acid target is detected using magnetic nanoparticles (MNPs) combined with an optomagnetic (OM) readout. Two RCA assays are developed with on-chip detection of rolling circle products (RCPs) either at end-point where MNPs are mixed with the sample after completion of RCA or in real time where MNPs are mixed with the sample during RCA. The plastic chip acts as a cuvette, which is positioned in a setup integrated with temperature control and simultaneous detection of four parallel DNA hybridization reactions between functionalized MNPs and products of DNA amplification. The OM technique probes the small-angle rotation of MNPs bearing oligonucleotide probes complementary to the repeated nucleotide sequence of the RCPs. This rotation is restricted when MNPs bind to RCPs, which can be observed as a turn-off of the signal from MNPs that are free to rotate. The amount of MNPs bound to RCPs is found to increase in response to the amplification time as well as in response to the synthetic DNA target concentration (2-40 pM dynamic range). We report OM real-time results obtained with MNPs present during RCA and compare to relevant end-point OM results for RCPs generated for different RCA times. The real-time approach avoids opening of tubes post-RCA and thus reduces risk of lab contamination with amplification products without compromising the sensitivity and dynamic range of the assay.

Rolling circle amplification (RCA) combined with padlock probe recognition of a DNA target is attractive for on-chip nucleic acid testing due to its high specificity and isothermal reaction conditions. However, the integration of RCA on an automated chip platform is challenging due to the different reagents needed for the reaction steps and the temperature sensitivity of the phi29 polymerase. Here, we describe the integration of an RCA assay on a single-use polymer chip platform where magnetic microbeads are used as solid support to transport the DNA target between three connected reaction chambers for (i) padlock probe annealing and ligation, (ii) RCA, and (iii) optomagnetic detection of RCA products. The three chambers were loaded with reagents by sequential filling combined with passive microfluidic structures. After loading, the on-chip assay steps were automated. For an assay in which all steps but the padlock probe annealing on the target were performed on-chip, we found a limit of detection (LOD) for a synthetic influenza target of 2 pM after 45 min of RCA, which is comparable to the corresponding laboratory assay. The entire assay, including padlock probe annealing, could be performed on-chip with an LOD of 20 pM after 45 min of RCA. This LOD can likely be reduced by further optimizing the microbead mixing. The results present important steps towards the integration and automation of RCA and potentially also other complex multi-step assays on a single-use polymer chip for molecular analysis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Padlock probe ligation-based rolling circle amplification (RCA) can distinguish single-nucleotide variants, which is promising for the detection of drug-resistance mutations in, e.g., Mycobacterium tuberculosis ( Mtb ). However, the clinical application of conventional linear RCA is restricted by its unsatisfactory picomolar-level limit of detection (LOD). Herein, we demonstrate the mechanism of a nicking-enhanced RCA (NickRCA) strategy that allows several polymerases to act simultaneously on the same looped template, generating single-stranded amplicon monomers. Limiting factors of NickRCA are investigated and controlled for higher amplification efficiency. Thereafter, we describe a NickRCA-based magnetic nanoparticle (MNP) dimer formation strategy combined with a real-time optomagnetic sensor monitoring MNP dimers. The proposed methodology is applied for the detection of a common Mtb rifampicin-resistance mutation, rpoB 531 (TCG/TTG). Without additional operation steps, an LOD of 15 fM target DNA is achieved with a total assay time of ca . 100 min. Moreover, the proposed biosensor holds the advantages of single-nucleotide mutation discrimination and the robustness to quantify targets in 10% serum samples. NickRCA produces short single-stranded monomers instead of the DNA coils produced in conventional RCA, which makes it more convenient for downstream operation, immobilization or detection, thus being applicable with different molecular tools and biosensors.

Rolling circle amplification (RCA) is a linear isothermal amplification technique that is widely applied in biomolecular assays due to its high specificity. Handling of a target sample using magnetic microbeads (MMBs) in a multi-step assay is appealing as the MMBs enable separation and transportation using an external magnet. Detection of amplicons using optomagnetic measurements of the rotational diffusion properties of magnetic nanoparticles (MNPs) is also appealing as it can be performed on any transparent sample container. Two strategies are described for integration of MMB sample handling in an RCA assay with on-chip optomagnetic detection of the amplification products. The first strategy relies on selective and irreversible release of the amplicons from the MMBs so that the binding of functionalized MNPs to the amplicons can be detected optomagnetically. The second strategy relies on the incorporation of MNPs into RCA products during RCA, followed by their separation on MMBs and subsequent optomagnetic detection upon release from the RCA products. Using MMB handling of RCA steps, the limits of detection (LODs) for a synthetic DNA target representative of Victoria Influenza type B were found to be between 4 and 20 pM with total assay times between 2 and 2.5 h. Without magnetic microbead sample handling, the LOD was 200 fM. The findings provide deeper insight into the use of magnetic microbeads as solid substrates to handle a DNA target for integration of RCA as well as other DNA-based assays. Graphical Abstract Schematic illustration of magnetic microbeads transporting a DNA target through the steps in a rolling circle amplification assay. Optomagnetic measurements detect the binding of magnetic nanoparticles to amplicons released from microbeads (top) or the pH-induced release of magnetic nanoparticles trapped in amplicons (bottom).

Burkholderia cepacia complex (Bcc) includes several phenotypically similar but genotypically distinct gram-negative bacteria (GNB) that can colonize the respiratory tract of Cystic Fibrosis (CF) patients. Pathogens are difficult to treat due to intrinsic resistance to multiple antibiotics and are associated to a more rapid decline in lung function and to increased mortality, particularly after lung transplantation. For all these reasons, chronic infection by Burkholderia (B) cenocepacia is presently considered a relative or absolute contraindication in almost all lung transplant centres. We report the case of a young adult CF patient chronically colonized by B multivorans genomovar II, with diabetes and end-stage renal disease treated with renal replacement therapy: a few months after lung transplantation, she developed post-surgery B multivorans bacteremia and multiple brain abscesses. This severe infection did not improve despite multiple standard antibiotic regimen. The introduction of ceftazidime-avibactam, a new β-lactam/ β-lactamase inhibitor combination resulted in clinical recovery and in radiological and biochemical improvement., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: To date, serological markers to monitor melanoma progression and response to therapy are lacking. In this context cytokines appear to be promising biomarkers of the disease., Objective: To compare cytokine and chemokine levels in melanoma patients and in healthy controls and to assess possible variations according to melanoma stage., Methods: Serum chemokine and cytokine levels were determined by ELISA in 34 patients diagnosed histologically of malignant melanoma. Seven healthy volunteers were used as controls., Results: We found a subset of cytokines (CCL3, CCL4, IFN-γ and IL-10) to be significantly higher in melanoma patients than in control group, thus confirming the importance of the inflammation in cancer. While CCL3 increased with tumor progression, IFN-γ and IL-10 showed higher levels in stage I patients. Moreover, we noticed a direct correlation between CCL3 level and the presence of ulceration in the primary tumor; on the contrary, CCL4, IL-10 and IFN-γ were lowered down in patients with ulcerated melanoma., Conclusions: These results expand and confirm observations made in other studies focusing on a more limited number of molecules. This extended panel of cytokines examines the potential roles of type2 cytokines (such as IL-4) and many chemokines (mainly CCL3) as biomarkers in melanoma progression.

Background: Among breastfeeding determinants, the marketing of breast milk substitutes might contribute to suboptimal breastfeeding rates. The aim of this study was to investigate the effect of receiving information on breast milk substitutes on breastfeeding rates., Methods: We conducted a randomized, single-blind, controlled trial from 2012 to 2014 in a northern Italian maternity ward. We enrolled 802 Caucasian mothers who gave birth to healthy, full-term singletons with a birth weight > 2500 g and who were exclusively breastfeeding from delivery to discharge. Mothers who gave birth to infants with congenital diseases, chromosomal abnormalities, perinatal infections and/or cardio-respiratory instability and/or mothers being affected by endocrine and/or metabolic and/or gastrointestinal and/or renal diseases were excluded. Mothers were randomized to either receive (group A, n = 405) or not (group B, n = 397) written information on a breast milk substitute at discharge. Breastfeeding was promoted and supported in all mother-infant pairs equally. The mode of feeding for up to 6 months after delivery was determined by phone interview. To detect a 10% difference between groups in the discontinuation rate of exclusive breastfeeding at three months of age at 5% significance and 80% power, a total of 356 mother-infant pairs per group were needed., Results: The exclusive breastfeeding prevalence was 91% and 92% at 7 days, 79% and 70% at 1 month, 75% and 66% at 2 months, 72% and 62% at 3 months, and 3% and 2% at 6 months in groups A and B, respectively. The relative risk (95% confidence interval) of exclusive breastfeeding (group A vs B) at 7 days and at 1, 2, 3 and 6 months was as follows: 0.99 (0.95-1.03), 1.12 (1.03-1.21), 1.13 (1.03-1.24), 1.15 (1.04-1.27), and 1.49 (0.62-3.61). Nutritional, lifestyle and lactational factors were the primary contributing determinants to early breastfeeding discontinuation., Conclusions: The present findings indicate that receiving written information on breast milk substitutes at hospital discharge, provided that breastfeeding support and education are offered, does not negatively affect breastfeeding rates., Trial Registration: NCT03208114. Registered 5 July 2017.

Objectives: To analyse the prevalence of CECR1 mutations in patients diagnosed with early onset livedo reticularis and/or haemorrhagic/ischaemic strokes in the context of inflammation or polyarteritis nodosa (PAN). Forty-eight patients from 43 families were included in the study., Methods: Direct sequencing of CECR1 was performed by Sanger analysis. Adenosine deaminase 2 (ADA2) enzymatic activity was analysed in monocyte isolated from patients and healthy controls incubated with adenosine and with or without an ADA1 inhibitor., Results: Biallelic homozygous or compound heterozygous CECR1 mutations were detected in 15/48 patients. A heterozygous disease-associated mutation (p.G47V) was observed in two affected brothers. The mean age of onset of the genetically positive patients was 24 months (6 months to 7 years). Ten patients displayed one or more cerebral strokes during their disease course. Low immunoglobulin levels were detected in six patients. Thalidomide and anti-TNF (tumour necrosis factor) blockers were the most effective drugs. Patients without CECR1 mutations had a later age at disease onset, a lower prevalence of neurological and skin manifestations; one of these patients displayed all the clinical features of adenosine deaminase 2deficiency (DADA2) and a defective enzymatic activity suggesting the presence of a missed mutation or a synthesis defect., Conclusions: DADA2 accounts for paediatric patients diagnosed with PAN-like disease and strokes and might explain an unrecognised condition in patients followed by adult rheumatologist. Timely diagnosis and treatment with anti-TNF agents are crucial for the prevention of severe complications of the disease. Functional assay to measure ADA2 activity should complement genetic testing in patients with non-confirming genotypes., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)