Salivary proteomic profile of young healthy subjects.

Background: The incidence of noncommunicable diseases (NCDs) has been rapidly ramped up worldwide. Hence, there is an urgent need to non-invasively detect NCDs possibly by exploiting saliva as a 'liquid biopsy' to identify biomarkers of the health status. Since, the absence of standardized procedures of collection/analysis and the lack of normal ranges makes the use of saliva still tricky, our purpose was to outline a salivary proteomic profile which features healthy individuals. Methods: We collected saliva samples from 19 young blood donors as reference population and the proteomic profile was investigated through mass-spectrometry. Results: We identified 1,004 proteins of whose 243 proteins were shared by all subjects. By applying a data clustering approach, we found a set of six most representative proteins across all subjects including Coronin-1A, F-actin-capping protein subunit alpha, Immunoglobulin J chain, Prosaposin, 78 kDa glucose-regulated protein and Heat shock 70 kDa protein 1A and 1B. Conclusion: All of these proteins are involved in immune system activation, cellular stress responses, proliferation, and invasion thus suggesting their use as biomarkers in patients with NCDs.

Hidradenitis suppurativa in Black and White patients - a clinical study.

OBJECTIVE: It is suggested that hidradenitis suppurativa (HS) is more prevalent and causes greater morbidity in Black patients than in White. Clinical data are however lacking. PATIENTS AND METHODS: We therefore describe HS risk factors, disease severity and clinical phenotypes in the Blacks and Whites. Patients referred for HS between 1984 and 2019 at the Johns Hopkins Hospital were identified using the Pathology Data System (PDS). Clinical and sociodemographic characteristics were extracted and the van der Zee & Jemec HS clinical phenotypes were recovered. RESULTS: A total of 278 patients were identified. Ethnically, 108 (38.8%) were White, and 170 (61.2%) Black. The following HS phenotypes were found: Regular (n=193, 69.4%), scarring folliculitis (n=40, 1.4%) frictional furuncle (11.2%), conglobata (n=9, 3.2%), syndromic (n=3, 1.1%) and ectopic (n=2, 0.7%). No statistically significant ethnic differences in clinical presentation were found. Blacks however had more severe diseases than Whites (p= 0.024 for trend). With multivariate logistic regression analysis, we found that male sex, disease duration, and smoking were independent predictors of regular HS phenotype. Major limitations are the limited number of cases studied and the lack of data regarding response to therapies. CONCLUSIONS: Demographics and phenotypical presentation of HS patients do not seem to be associated with Black ethnicity. However, there is a significant trend for Blacks to present with more Hurley stage 2 and 3 disease compared to White patients. It is speculated that ethnic differences are epiphenomena to social factors, highlighting the broader importance of ethnicity.

Machine learning to predict overall short-term mortality in cutaneous melanoma.

BACKGROUND: Cutaneous malignant melanoma (CMM) ranks among the ten most frequent malignancies, clinicopathological staging being of key importance to predict prognosis. Artificial intelligence (AI) has been recently applied to develop prognostically reliable staging systems for CMM. This study aims to provide a useful machine learning based tool to predict the overall CMM short-term survival. METHODS: CMM records as collected at the Veneto Cancer Registry (RTV) and at the Veneto regional health service were considered. A univariate Cox regression validated the strength and direction of each independent variable with overall mortality. A range of machine learning models (Logistic Regression classifier, Support-Vector Machine, Random Forest, Gradient Boosting, and k-Nearest Neighbors) and a Deep Neural Network were then trained to predict the 3-years mortality probability. Five-fold cross-validation and Grid Search were performed to test the best data preprocessing procedures, features selection, and to optimize models hyperparameters. A final evaluation was carried out on a separate test set in terms of balanced accuracy, precision, recall and F1 score. The best model was deployed as online tool. RESULTS: The univariate analysis confirmed the significant prognostic value of TNM staging. Adjunctive clinicopathological variables not included in the AJCC 8th melanoma staging system, i.e., sex, tumor site, histotype, growth phase, and age, were significantly linked to overall survival. Among the models, the Neural Network and the Random Forest models featured the best prognostic performance, achieving a balanced accuracy of 91% and 88%, respectively. According to the Gini importance score, age, T and M stages, mitotic count, and ulceration appeared to be the variables with the greatest impact on survival prediction. CONCLUSIONS: Using data from patients with CMM, we developed an AI algorithm with high staging reliability, on top of which a web tool was implemented ( unipd.link/melanomaprediction ). Being essentially based on routinely recorded clinicopathological variables, it can already be implemented with minimal effort and further tested in the current clinical practice, an essential phase for validating the model's accuracy beyond the original research context.

Hospital networks in Italy: state of the art and future pespectives. Insights from a qualitative research study.

Background Hospitals have undergone important that changes that have led, in recent decades at the international level, to the need for greater integration between hospitals and local healthcare services. The main institutional networks that have been developed in Italy are, as commended by the institutional levels, of 4 main types: the Emergency-Urgency Network, the Time-Dependent Networks, the Oncological Networks, and the Networks with primary care settings. It was important to assess the state of the art and analyze it in relation to possible future developments. Objective The aim of the study was to collect insights from both evidence-based knowledge and personal experience gained by experts in the field regarding the current condition and possible future developments of hospital networks. Material and methods A qualitative research methodology was chosen. Four mini-focus group meetings were organized among participants with proven expertise on the subject. Discussions were guided by four open-ended questions corresponding to the four areas of interest. Directed content analysis was chosen as the methodology for data analysis and final reporting of results. Results Four main categories were explored: "hospital networks and complexity", "hospital networks complexity and the need for integration", "levers for hospital networks governance" and "the COVID-19 challenge and future developments for hospital networks". In particular, the participants found that it is important to understand healthcare systems as complex systems and, therefore, to study the properties of complex systems. In this way it is possible to achieve value-based healthcare in complex contexts. It is also necessary to keep in mind that complexity represents a challenge for coordination/ integration in hospital networks. Mintzberg identified specific mechanisms to achieve it. Of them, mutual adaptation is the key to self-organization. Valentijn showed the organizational levels on which coordination/integration has to be obtained. Hospital network governance should include both hierarchy and self-determination logic to achieve integration in each of the four levels. The participants identified three key levers for governing complex organizations: "education", which consists of multi-professional and multi-level training in governance in complex systems; "information" consisting in considering the data registering as an integral part of the clinical care process to informative value; "leadership", which consists in convincing actors, directed towards personal gains, to achieve valuable goals. Finally, the challenge that COVID-19 served as an incentive for future developments of hospital networks. Discussion Various common points between the definitions of network and complex systems can be found. It is important to study the properties of complex systems in order to achieve value-based healthcare in the hospital networks context. The insights gained should be useful for all professionals from and across all levels of healthcare organizational responsibility, being able to orient roles and actions to achieve coordination/integration inside hospital networks. Conclusions Complexity literature can help understand how to achieve coordination/integration in healthcare settings and find levers for effective governance. It is important to study the current situation to anticipate and, possibly govern, future developments. In conclusion, governance of hospital networks should be interpreted as coordination/integration inside and across multiple organizational levels of co-responsibility.

Educational Interventions for Promoting Food Literacy and Patient Engagement in Preventing Complications of Type 2 Diabetes: A Systematic Review.

The present review aims to map the current literature on educational interventions to promote food literacy in type 2 diabetes, with a particular focus on the concept of patient engagement. The systematic review was implemented on five databases with no restrictions on the publication year. The studies selected for the review were focused on patients with type 2 diabetes, ranging from 2003 to 2021 and published in 13 countries (44% USA). Thirty-three articles were analyzed. Twenty-seven articles targeted singular patients; fifteen articles conceptualized patient engagement as self-management. In seven articles, the provider is a multidisciplinary team. Twenty articles did not report a theoretical framework in the intervention development, and eleven did not use an intervention material. Twenty-six articles did not use a technology proxy. Outcome categories were narratively mapped into four areas: clinical, psychological, behavioral, and literacy. To date, most of the interventions are heterogeneous in the adopted methodology, measures, and outcomes considered. More attention should be given to the psychosocial characterization of patient engagement as well as the technological support. High-quality, randomized controlled trials and longitudinal studies are lacking and need to be conducted to verify the efficacy of these insights.

Big data highlights the association between psoriasis and fibromyalgia: a population-based study.

Data on the association between fibromyalgia syndrome (FMS) and psoriasis are scarce. We aimed to examine the association between FMS and psoriasis using a large-scale observational population-based study. This cross-sectional study analyzed data from a big computerized database to evaluate potential differences in the prevalence of psoriasis between patients with FMS and matched control subjects. The study included 18,598 patients with FMS and 36,985 controls. The prevalence of psoriasis was increased in patients with FMS as compared with control subjects (6.7% vs. 4.8%, respectively; OR, 1.4; 95% CI, 1.3-1.5; P < 0.001). This association was robust to multivariate analysis adjustment for sex, age, ancestry, socioeconomic status, and healthcare utilization (OR, 1.3; 95% CI, 1.2-1.4; P < 0.001). When compared with patients with only FMS, patients with a dual diagnosis of FMS and psoriasis presented with FMS at a significantly older age, had a higher mean BMI, and a higher frequency of smoking. To conclude, we found a significant association between FMS and psoriasis. More extensive cooperation between dermatologists and rheumatologists is suggested to enable early identification of their co-occurrence.

Artificial neural networks allow response prediction in squamous cell carcinoma of the scalp treated with radiotherapy.

BACKGROUND: Epithelial neoplasms of the scalp account for approximately 2% of all skin cancers and for about 10-20% of the tumours affecting the head and neck area. Radiotherapy is suggested for localized cutaneous squamous cell carcinomas (cSCC) without lymph node involvement, multiple or extensive lesions, for patients refusing surgery, for patients with a poor general medical status, as adjuvant for incompletely excised lesions and/or as a palliative treatment. To date, prognostic risk factors in scalp cSCC patients are poorly characterized. OBJECTIVE: To identify patterns of patients with higher risk of postradiotherapy recurrence. METHODS: A retrospective observational study was performed on scalp cSCC patients with histological diagnosis who underwent conventional radiotherapy (50-120 kV) (between 1996 and 2008, follow-up from 1 to 140 months, median 14 months). Out of the 79 enrolled patients, 22 (27.8%) had previously undergone a surgery. Two months after radiotherapy, 66 (83.5%) patients achieved a complete remission, 6 (7.6%) a partial remission, whereas 2 (2.5%) proved non-responsive to the treatment and 5 cases were lost to follow-up. Demographical and clinical data were preliminarily analysed with classical descriptive statistics and with principal component analysis. All data were then re-evaluated with a machine learning-based approach using a 4th generation artificial neural networks (ANNs)-based algorithm. RESULTS: Artificial neural networks analysis revealed four scalp cSCC profiles among radiotherapy responsive patients, not previously described: namely, (i) stage T2 cSCC type, aged 70-80 years; (ii) frontal cSCC type, aged <70 years; (iii) non-recurrent nodular or nodulo-ulcerated, stage T3 cSCC type, of the vertex and treated with >60 Grays (Gy); and (iv) flat, occipital, stage T1 cSCC type, treated with 50-59 Gy. The model uncovering these four predictive profiles displayed 85.7% sensitivity, 97.6% specificity and 91.7% overall accuracy. CONCLUSIONS: Patient profiling/phenotyping with machine learning may be a new, helpful method to stratify patients with scalp cSCCs who may benefit from a RT-treatment.

Photoadaptation to ultraviolet B TL01 in psoriatic patients.

BACKGROUND: In the biologic era, narrow-band ultraviolet B (NB-UVB) phototherapy still remains a valuable, effective, inexpensive, safe anti-psoriatic treatment. Patients can lose response to NB-UVB over time due to photoadaptation. This phenomenon is the tendency of the skin to respond to ultraviolet (UV) exposure by undergoing changes that may result in a decreased future response to an equivalent dose of radiation, thus leading to the need for an increased exposure during phototherapy course. AIM: To characterize and quantify the determinants of photoadaptation in NB-UVB treated psoriatic patients. METHODS: We enrolled 57 adult patients with moderate plaque psoriasis. Patients underwent 24 sessions of NB-UVB phototherapy delivered thrice a week. Dosing was started with 70% of the minimal erythema dose (MED) with percentage-based dose increments every two treatments. MED as well as change in the erythema and melanin index (MI) were measured at baseline and at the end of phototherapy course. Moreover, an adaptation factor (AF) was calculated for each patient. RESULTS: Adaptation factor was not influenced by both baseline MED and skin type. We found a weak correlation between higher cumulative dosages and the initial MED (Spearman's rho = 0.32, P = 0.0154) as well as with the mean initial MI (Spearman's rho = 0.25, P = 0.0624, statistically borderline). Clearance and mean number of treatments were correlated (Spearman's rho = 0.48, P < 0.001). CONCLUSION: Photoadaptation is a physiological skin response that negatively influences NB-UVB responsiveness and is not predictable by the baseline MED and skin type. Thus, starting with more aggressive protocols and increasing rapidly dosage progression to prevent AF may increase NB-UVB response.

Epidemiology of odontogenic sinusitis: an old, underestimated disease, even today. A narrative literature review.

Odontogenic sinusitis is an inflammatory condition of the paranasal sinuses resulting from dental pathology. The aim of this study is to provide an overview of the current literature on the dimensions of the phenomenon, quality of life, economic considerations, and approaches to odontogenic sinusitis. A narrative review was conducted following the methodology proposed by Green et al. (2006). There appears to have been an increase in the incidence over the last decade. Nowadays, evidence in the literature reports that 10-12% up to 40% of all sinusitis cases are associated with odontogenic infections. The iatrogenia was by far the leading cause of odontogenic sinusitis (55.97%) while the first and second molars were the most affected teeth with an incidence of 35.6% and 22%. If not properly diagnosed and treated, these infections may lead to a rapid spread, giving rise to potentially life-threatening complications with a significant general health-related Quality of Life detriment. The proper management of patients in a pre-implant logical setting leads to substantial savings, ranging from €38 million to €152 million, for the Italian National Health Service. Odontogenic sinusitis management should involve shared decisionmaking between the otolaryngologist, dental provider, and patient, where the benefits and risks of dental treatment and endoscopic sinus surgery are discussed.

Psoriatic and psoriatic arthritis patients with and without jet-lag: does it matter for disease severity scores? Insights and implications from a pilot, prospective study.

Background: Jet-lag may affect air-travelers crossing at least two time-zones and has several health-care implications. It occurs when the human biological rhythms are out of synch with respect to the day-night cycle at the country destination. Its effect in psoriasis is missing. We aimed to evaluate the effect of Jet-lag in psoriatic patients' management. Methods: This is a prospective observational study that enrolled psoriatic patients that underwent a flight: patients who experienced jet-lag were compared to patients who did not experience jet-lag. Before the flight, a dermatologist recorded clinical and demographical data with particular attention to Psoriasis Area Severity Index (PASI) and Disease Activity in Psoriatic Arthritis (DAPSA). Patients performed Self-Administered Psoriasis Area Severity Index (SAPASI), the Dermatology Life Quality Index (DLQI) and the pruritus Visual Analog Scale (VAS) scores. After the flight, patients completed the SAPASI, DLQI and pruritus-VAS scores. Results: The sample recruited comprised of 70 psoriatic patients aged 42.4 ± 9.7 years (median 42.5 years). Thirty (42.9%) were males, mean BMI was 25.5 ± 2.2 kg/m2. Average disease duration was 15.2 ± 7.1 years, and 20 (28.6%) subjects had developed PsA. Average hours of flight were 5.4 ± 3.5 (median 3.5 h), with 34 (48.6%) subjects reporting jet-lag. At the multivariate regression analysis, the change in the SAPASI score resulted correlated with jet-lag (regression coefficient 1.63, p = .0092), as well the change in the DLQI score (regression coefficient = 1.73, p = .0009), but no change on the pruritus VAS scale was found. Conclusions: The present study suggests that jet-lag may influence disease severity and DLQI scores, but not itch in psoriatic patients.

'High dose' vs. 'medium dose' UVA1 phototherapy in italian patients with severe atopic dermatitis.

BACKGROUND: The current evidences attest UVA1 phototherapy as effective in the treatment of severe atopic dermatitis (AD). Furthermore, in this indication, 'medium dose' is as effective as 'high dose' regimen. To date, a randomized comparison study evaluating the effectiveness as well as safety of different UVA1 protocols in different skin types in the treatment of adult patients with severe AD is still lacking. OBJECTIVE: The aim of the present study was to compare the safety and the efficacy of medium and high dose UVA1 either in fair or in dark skin types. METHODS: Twenty-seven adult patients with severe AD were consecutively included in a randomized, controlled, open, two arms trial Severity of AD was determined by means of SCORAD index and clinical improvement was also monitored. A total of 13 out of 27 patients were treated with high dose (130 J/cm2 ) UVA1 protocol while 14 out of 27 patients received medium dose (60 J/cm2 ) UVA1 protocol. Phototherapy was performed five times weekly up to 3 weeks. Before and after UVA1 treatment each patient was evaluated for skin pigmentation through Melanin Index (MI) quantitative evaluation. RESULTS: Skin status improved in all patients resulting in a reduction of SCORAD index in all groups. Our results demonstrated that among patients with darker skin types and higher MI, high dose UVA1 was significantly more effective than medium dose (P < 0.0001) while within the groups with skin type II, no significant differences between high and medium dose protocols were observed. CONCLUSION: Our study, confirms previous observations that UVA1 phototherapy should be considered among the first approaches in the treatment of patients with severe generalized AD and also demonstrates that in darker skin types, high dose UVA1 phototherapy is more effective than medium dose in the treatment of adult patients with severe AD.

Autoinflammation in pyoderma gangrenosum and its syndromic form (pyoderma gangrenosum, acne and suppurative hidradenitis).

BACKGROUND: Pyoderma gangrenosum (PG) is a rare skin disease characterized clinically by ulcers with undermined borders, and histologically by neutrophil-rich infiltrates. PG may occur alone, in syndromic forms or associated with systemic diseases, such as inflammatory bowel disease and haematological or rheumatological disorders. OBJECTIVES: To determine a specific genetic background related to autoinflammation for PG. METHODS: We assessed autoinflammation by evaluating the cytokine profile and genes involved in classic autoinflammatory diseases in 13 patients with PG and in seven patients with the syndromic form, known as PASH (pyoderma gangrenosum, acne and suppurative hidradenitis). RESULTS: In skin samples, the expression of interleukin (IL)-1ß and its receptors, IL-17 and its receptor, and tumour necrosis factor-α and its receptors were significantly higher in both PG (P = 0·001) and in PASH (P < 0·001) than in controls. The chemokines IL-8; chemokine (C-X-C motif) ligand 1/2/3; chemokine (C-X-C motif) ligand 16; and RANTES (regulated on activation, normal T-cell-expressed and secreted) were also overexpressed. Cases of PG and PASH showed mutations in the autoinflammatory genes MEFV, NLRP3, NLRP12, NOD2, LPIN2 and PSTPIP1. CONCLUSIONS: Overexpression of cytokines/chemokines, along with genetic changes, supports the hypothesis that PG and its syndromic form, PASH, are a spectrum of polygenic autoinflammatory conditions.

Determinants of out-of-hours service users' potentially inappropriate referral or non-referral to an emergency department: a retrospective cohort study in a local health authority, Veneto Region, Italy.

BACKGROUND: A growing presence of inappropriate patients has been recognised as one of the main factors influencing emergency department (ED) overcrowding, which is a very widespread problem all over the world. On the other hand, out-of-hours (OOH) physicians must avoid delaying the diagnostic and therapeutic course of patients with urgent medical conditions. The aim of this study was to analyse the appropriateness of patient management by OOH services, in terms of their potentially inappropriate referral or non-referral of non-emergency cases to the ED. METHODS: This was an observational retrospective cohort study based on data collected in 2011 by the local health authority No. 4 in the Veneto Region (Italy). After distinguishing between patients contacting the OOH service who were or were not referred to the ED, and checking for patients actually presenting to the ED within 24 hours thereafter, these patients' medical management was judged as potentially appropriate or inappropriate. RESULTS: The analysis considered 22 662 OOH service contacts recorded in 2011. The cases of potentially inappropriate non-referral to the ED were 392 (1.7% of all contacts), as opposed to 1207 potentially inappropriate referrals (5.3% of all contacts). Age, nationality, type of disease and type of intervention by the OOH service were the main variables associated with the appropriateness of patient management. CONCLUSIONS: These findings may be useful for pinpointing the factors associated with a potentially inappropriate patient management by OOH services and thus contribute to improving the deployment of healthcare and the quality of care delivered by OOH services.

Conventional fascial technique versus mesh repair for advanced pelvic organ prolapse: Analysis of recurrences in treated and untreated compartments.

117 women with severe pelvic organ prolapse (POP; stage > 2) were enrolled to elucidate a 24-month outcome of POP surgery, using conventional or mesh repair with 3 techniques. 59 patients underwent conventional repair and 58 underwent mesh repair. Two types of mesh were used: a trocar-guided transobturator polypropylene (Avaulta, Bard Inc.) and a porcine dermis mesh (Pelvisoft, Bard Inc.). Women with recurrences, who underwent previous unsuccessful conventional repair, were randomised. Primary outcome was the evaluation of anatomic failures (prolapse stage > 1) in treated and untreated compartments. Anatomic failure was observed in 11 of 58 patients (19%; CI 8.9-29) in the mesh group and in 16 of 59 patients (27.1%; p value = 0.3) in the conventional group. 9 of 11 failures in the mesh group (15.5%; CI 6.2-24.8) were observed in the untreated compartment (de novo recurrences), 14.3% in Pelvisoft and 16.7% in Avaulta arm, while only 1 recurrence in the untreated compartment (1.7%) was observed in the conventional group (odds ratio 10.6, p = 0.03).

Matter of margins.

BACKGROUND: Basal cell carcinoma (BCC) is the most common cancer, it represents a significant economic burden to health services because of a large volume of affected patients. Surgical excision with histological assessment of the surgical margins is widely considered as the mainstay of BCC treatment. Incomplete removal, in fact, should be considered a poor prognostic indicator, as incomplete removal of lesions is at risk of local recurrence. Actually, dermatological surgeries are carried out by a variety of different types of practitioners, such as plastic surgeons, maxillofacial surgeons, otorhinolaryngologists, ophthalmologists and finally dermatologists. Incomplete removal of the tumour ranges from 6.3% to 25%, depending on the improper intra-operative evaluation of the extent of the tumour. It depends on the clinical knowledge derived from both training and daily experience. In this sense, the majority of the largest studies derive from plastic surgeons, while dermatologists have small case series, albeit with a higher therapeutic efficacy in terms of complete surgical excision. OBJECTIVES: We conducted a retrospective analysis of the surgical activity, more specifically we evaluated both our therapeutic accuracy and analyzed the prognostic factors related to incomplete excisions. METHODS: A retrospective review of all BCC removals was performed. A total of 4523 BCC removals were included; other neoplasm, benign lesions and biopsies were also excluded. Each BCC's size diameter, localization, histology and histological presence of complicating factors was assessed, then the percentage of the incomplete removal was calculated. RESULTS: Incomplete resections occurred in 225 (4.97%) BCCs of the cases. Thirteen areas were categorized into in three different levels that rank the risk of incomplete removals. Sub-analysis indicates that just over a third had no complicating factors with the lateral/deep margins. The most frequent complicating factor is ulceration (22.9%), while vascular invasion or seborrheic keratoses were not found. Actinic keratoses, scabs and scars held the most responsibility for the involvement of the lateral margins, while perineural invasion is the main factor leading to deep margin involvement. Finally, a different trend for the involvement of lateral or deep margins according different histological sub-types was highlighted; lateral involvement is more frequent for the infiltrative/morpheic type, while the deep margin is more involved in the nodular type.