Transformation of Cancer Care during and after the COVID Pandemic, a point of no return. The Experience of Italy.

Policymakers everywhere struggle to introduce therapeutic innovation while controlling costs, a particular challenge for the universal Italian National Healthcare System (SSN), which spends only 8.8% of GDP to care for one of the world's oldest populations. Oncology provides a telling example, where innovation has dramatically improved care and survival, transforming cancer into a chronic condition. However, innovation has also increased therapy duration, adverse event management, and service demand. The SSN risks collapse unless centralized cancer planning changes gear, particularly with Covid-19 causing treatment delays, worsening patient prognosis and straining capacity. In view of the 750 billion Euro "Next Generation EU", released by the European Union to relieve Member States hit by the pandemic, the SSN tapped a multidisciplinary research team to identify key strategies for equitable uptake of innovations in treatment and delivery, with emphasis on data-driven technological and managerial advancements - and lessons from Covid-19.

Mitigating strategies and nursing response for cancer care management during the COVID-19 pandemic: an Italian experience.

AIM: To describe our response to the COVID-19 emergency in a cancer centre to enable other nursing organizations to determine which elements could be useful to manage a surge of patients in their own setting. BACKGROUND: The COVID-19 pandemic represents one of the most challenging healthcare scenarios faced to date. Managing cancer care in such a complex situation requires a coordinated emergency action plan to guarantee the continuity of cancer treatments for patients by providing healthcare procedures for patients, caregivers and healthcare professionals in a safe environment. PROCEDURES: We describe the main strategies and role of nurses in implementating such procedures. RESULTS: Nurses at our hospital were actively involved in COVID-19 response defined by the emergency action plan that positively contributed to correct social distancing and to the prevention of the spread of the virus. IMPLICATIONS FOR NURSING AND HEALTH POLICIES: Lessons learned from the response to phase I of COVID-19 have several implications for future nursing and health policies in which nurses play an active role through their involvement in the frontline of such events. Key policies include a coordinated emergency action plan permitting duty of care within the context of a pandemic, and care pathway revision. This requires the rapid implementation of strategies and policies for a nursing response to the new care scenarios: personnel redistribution, nursing workflow revision, acquisition of new skills and knowledge, effective communication strategies, infection control policies, risk assessment and surveillance programmes, and continuous supplying of personal protective equipment. Finally, within a pandemic context, clear nursing policies reinforcing the role of nurses as patient and caregiver educators are needed to promote infection prevention behaviour in the general population.

Microbiological evaluation of environmental cleanliness in haematopoietic cell transplant patient rooms: implementing JACIE standards.

BACKGROUND: Environmental hygiene is one of the most important strategies to prevent hospital-acquired infections by reducing pathogens in haematopoietic cell transplant (HCT) patient rooms. This study was designed in response to JACIE requirements for microbiological monitoring, and aimed to assess environmental hygiene in protective isolation rooms. METHODS: Environmental cleanliness was assessed by measuring microbial loads in at-rest and operational conditions sampled from target surfaces, and in passive and active air from rooms occupied by patients with different grades of neutropenia. The study also evaluated whether microbial loads were influenced by isolation precautions. RESULTS: The failure rate of cleanliness on target surfaces in at-rest conditions was 0% compared with 37% for surfaces and 13% for passive and active air samples in operational conditions. Differences in failure rates were observed in the rooms of patients with different levels of neutropenia (P=0.036 for surfaces, 0.028% for passive air). No relationship was found between infections and microbial loads. CONCLUSIONS: Microbiological assessment integrated with an enhanced monitoring programme for hospital hygiene provides invaluable information to drive infection control policies in HCT patients. These results highlight the need to set and validate strict standards for the assessment of cleanliness in a clinical setting.

Costs of irritable bowel syndrome in European countries with universal healthcare coverage: a meta-analysis.

OBJECTIVE: To provide an overall estimate of the direct, indirect and total costs of irritable bowel syndrome (IBS) for the adult population of the European countries with universal healthcare coverage. MATERIALS AND METHODS: We searched MedLine and Scopus databases (up to September 2018) to identify the European studies that evaluated the economic impact of IBS. Mean annual direct, indirect and total per-capita IBS costs were estimated using random-effect single-group meta-analyses of continuous data. All analyses were stratified by payer category (governments, insurance, societal), and the results were expressed as summary mean and 95% CI. RESULTS: A total of 24 studies were included in the meta-analyses. Only two studies evaluated IBS costs in Italy. The pooled summary of direct IBS per-capita cost, obtained from 23 European datasets (n=15,157), was €1837/year (95% CI: 1480-2195), with large differences across payers (from €1183 to €3358, in countries with publicly-funded and insurance-based health systems, respectively). The mean indirect cost, extracted from 13 datasets (n=3978), was €2314/year (95% CI: 1811-2817), again with wide differences across payers. Finally, the meta-analysis estimating the total annual cost, based upon 11 European datasets (n=2757), yielded a summary estimate of €2889/year (95% CI: 2318-3460) per patient, ranging from €1602 (insurance-based health systems) to €3909 (studies adopting a societal perspective). CONCLUSIONS: Considering a conservative estimate of 2,736,700 Italian adults affected by the syndrome, the minimum costs due to IBS in Italy - likely underestimated - range from 6 to 8 billion euro per year. Given the substantial economic burden for patients, healthcare systems and society, IBS should be included among the priorities of the public health agenda.

Basal cell carcinoma, squamous cell carcinoma and melanoma of the head and face.

Ultraviolet light (UV) is an important risk factor for cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma of the skin. These cancers most commonly affect persons with fair skin and blue eyes who sunburn rather than suntan. However, each of these cancers appears to be associated with a different pattern of UV exposure and to be mediated by different intracellular molecular pathways.Some melanocortin 1 receptor (MC1R) gene variants play a direct role in the pathogenesis of cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma apart from their role in determining a cancer-prone pigmentory phenotype (fair skin, red hair, blue eyes) through their interactions with other genes regulating immuno-inflammatory responses, DNA repair or apoptosis.In this short review we focus on the aetiological role of UV in cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma of the skin, and on some associated biopathological events.

Oral mucosal melanoma: some pathobiological considerations and an illustrative report of a case.

Oral mucosal melanoma is a relatively rare malignancy with an aggressive clinico-pathological behaviour. The mean 5-year survival rate is about 15 %. It arises primarily from melanocytes found in the basal cell layer of the epithelium, but may sometimes arise from melanocytes residing in the lamina propria. The pathogenesis is complex, and few of the molecular mechanisms underlying the development of oral mucosal melanoma have been defined. The extraneous risk factors associated with oral mucosal melanoma, if any, are unknown. Oral mucosal melanomas account for about 25 % of all mucosal melanomas of the head and neck, and exhibit a profile of cytogenetic alterations, and a pathobiological behaviour and clinical course different from that of cutaneous melanomas. As they are usually painless and grow quickly, as a rule, they are diagnosed late in the course of the disease when the lesions are already large and have metastasized to regional lymph nodes. In this paper we discuss some aspects of the pathobiology of oral mucosal melanoma, and present an illustrative case report.

Radiolucent inflammatory implant periapical lesions: a review of the literature.

PURPOSE: To discuss the terminology, etiopathogenesis, and treatment of radiolucent inflammatory implant periapical lesions. MATERIALS AND METHODS: An electronic search for relevant articles published in the English literature in the PubMed database. RESULTS: Bacterial contamination of the apical portion of the implant either from a preexisting dental periapical infection or from a periapical lesion of endodontic origin of an adjacent tooth is the probable causative factor. Aseptic bone necrosis owing to overheating of the bone during preparation of osteotomies, or compression of the bone at the apex of the implant owing to excessive tightening, may also play a role. The histopathological features are of a mixed inflammatory cell infiltrate on a background of granulation tissue consistent with either a granuloma or an abscess as may be found at the apex of a nonvital tooth. Treatment consists of immediate and aggressive surgical debridement, chemical detoxification of the apical portion of the exposed implant surface, and systemic antibiotics with or without a bone regenerative procedure. CONCLUSION: A radiolucent inflammatory implant periapical lesion is analogous to either a granuloma or an abscess as may be found at the apex of a nonvital tooth.

A clinico-pathologic review of 56 cases of ossifying fibroma of the jaws with emphasis on the histomorphologic variations.

OBJECTIVE: This study aims at contributing to the definitive diagnosis of ossifying fibroma (OF) based on histomorphological features. The study also aims to determine some demographic features of OF, common sites of occurrence and to determine whether behavior correlates well with the histomorphological variations seen in the lesion. MATERIALS AND METHODS: A total of 80 patients who were diagnosed either as cementifying fibroma CF, OF and cemento-ossifying fibroma (COF) of the jaws from the files of the Oral Pathology Department of the University of the Witwatersrand Dental School were retrieved and the histology slides of each case were reviewed with the most recent diagnostic criteria for OF and the authors additional criteria. A total of 56 cases that met the set criteria were analyzed. RESULTS: The patients were clustered within the third and fourth decades of life ( n = 39, 69.6%). Majority of the patients were black (83.93%), whereas the rest were whites (12.50%) and Asians (3.57%). There were 17 males (30.4%) and 39 females (69.6%), giving a male to female ratio of 1:2.3. Most of the lesions (70.3%) occurred in the mandible, involving the premolar molar region (56.7%). Scanty fibrous tissues in highly cellular lesions were found in 36 (64.3%) of the cases. There were globular, dystrophic or granular calcifications mixed with irregularly shaped trabeculae of lamellar or cellular woven bone or osteoid were found, in 36 (64.3%) cases. CONCLUSION: Demographic data, clinicoradiologic features, combined with histopathology will continue to be relevant in the definitive diagnosis of OF and in predicting its behavior. Highly aggressive lesions with shorter duration in people below 15 years were called juvenile OF and treated as such, while OF applies to other conventional ones.

Automatic heart rate normalization for accurate energy expenditure estimation. An analysis of activities of daily living and heart rate features.

INTRODUCTION: This article is part of the focus theme of Methods of Information in Medicine on "Pervasive Intelligent Technologies for Health". BACKGROUND: Energy Expenditure (EE) estimation algorithms using Heart Rate (HR) or a combination of accelerometer and HR data suffer from large error due to inter-person differences in the relation between HR and EE. We recently introduced a methodology to reduce inter-person differences by predicting a HR normalization parameter during low intensity Activities of Daily Living (ADLs). By using the HR normalization, EE estimation performance was improved, but conditions for performing the normalization automatically in daily life need further analysis. Sedentary lifestyle of many people in western societies urge for an in-depth analysis of the specific ADLs and HR features used to perform HR normalization, and their effects on EE estimation accuracy in participants with varying Physical Activity Levels (PALs). OBJECTIVES: To determine 1) which low intensity ADLs and HR features are necessary to accurately determine HR normalization parameters, 2) whether HR variability (HRV) during ADLs can improve accuracy of the estimation of HR normalization parameters, 3) whether HR normalization parameter estimation from different ADLs and HR features is affected by the participants' PAL, and 4) what is the impact of different ADLs and HR features used to predict HR normalization parameters on EE estimation accuracy. METHODS: We collected reference EE from indirect calorimetry, accelerometer and HR data using one single sensor placed on the chest from 36 participants while performing a wide set of activities. We derived HR normalization parameters from individual ADLs (lying, sedentary, walking at various speeds), as well as combinations of sedentary and walking activities. HR normalization parameters were used to normalized HR and estimate EE. RESULTS: From our analysis we derive that 1) HR normalization using resting activities alone does not reduce EE estimation error in participants with different reported PALs. 2) HRV features did not show any significant improvement in RMSE. 3) HR normalization parameter estimation was found to be biased in participants with different PALs when sedentary-only data was used for the estimation. 4) EE estimation error was not reduced when normalization was carried out using sedentary activities only. However, using data from walking at low speeds improved the results significantly (30-36%). CONCLUSION: HR normalization parameters able to reduce EE estimation error can be accurately estimated from low intensity ADLs, such as sedentary activities and walking at low speeds (3 - 4 km/h), regardless of reported PALs. However, sedentary activities alone, even when HRV features are used, are insufficient to estimate HR normalization parameters accurately.

Continuity of care of cancer patients. Analysis of theoretical models and survey tools of continuity of care in people with a cancer diagnosis.

BACKGROUND: The Italian Ministry of Health declared oncology a priority and stressed the importance of ensuring continuity and integration in cancer care pathways. In order to monitor the quality of cancer care pathways, we need to explore patients' experience of the continuity of care, identifying the dimensions that define continuity. METHODS: We found 886 relevant articles in the Pubmed database from 1987 to 5 November 2013. The search strategy for the electronic database was defined using the Population, Intervention, Comparison and Outcome(s) framework (PICO) to identify keywords. Two researchers independently reviewed records identified through the search strategy, analyzing continuity dimensions, specificity and/or transversal domains. RESULTS: We selected 20 articles that measure the patients' experience of continuity of care: 7 articles including 5 questionnaires [Questionnaire by King et al. 2008; Cancer care coordination Questionnaire (Cccq); Patient Continuity of Care Questionnaire (Pccq); Medical Care Questionnaire (Mcq); Continuity and Coordination of Care Questionnaire (CCCQ)]; 6 articles evaluating the relationship between patient and his/her physician (the same across the care pathway) in terms of frequency and/or dispersion; 6 articles considering one subscale of larger scales designed to evaluate the generic cancer care service patient experience; 1 revealing four organizational indicators of care pathway continuity / discontinuity. CONCLUSIONS: We traced 3 transversal dimensions across the individual analyses: informational, organizational, relational continuity. It follows that in order to cater to the needs of cancer patients, we need to simultaneously focus on these three dimensions along the cancer care pathway. In line with these results, we promoted the "R.In.Cu.ORAM.i" study (Networks for Integrated Treatment of colorectal and breast cancer), in Area Vasta Romagna Area (Italy), and developed a continuity of care patient-experience continuity tool.

Oral candidosis in relation to oral immunity.

Symptomatic oral infection with Candida albicans is characterized by invasion of the oral epithelium by virulent hyphae that cause tissue damage releasing the inflammatory mediators that initiate and sustain local inflammation. Candida albicans triggers pattern-recognition receptors of keratinocytes, macrophages, monocytes and dendritic cells, stimulating the production of IL-1ß, IL-6 and IL-23. These cytokines induce the differentiation of Th17 cells and the generation of IL-17- and/or IL-22-mediated antifungal protective immuno-inflammatory responses in infected mucosa. Some immune cells including NKT cells, γδ T cells and lymphoid cells that are innate to the oral mucosa have the capacity to produce large quantities of IL-17 in response to C. albicans, sufficient to mediate effective protective immunity against C. albicans. On the other hand, molecular structures of commensal C. albicans blastoconidia, although detected by pattern-recognition receptors, are avirulent, do not invade the oral epithelium, do not elicit inflammatory responses in a healthy host, but induce regulatory immune responses that maintain tissue tolerance to the commensal fungi. The type, specificity and sensitivity of the protective immune response towards C. albicans is determined by the outcome of the integrated interactions between the intracellular signalling pathways of specific combinations of activated pattern-recognition receptors (TLR2, TLR4, Dectin-1 and Dectin-2). IL-17-mediated protective immune response is essential for oral mucosal immunity to C. albicans infection.

Oral medicine case book 65: Necrotising stomatitis.

Necrotising stomatitis is a fulminating anaerobic polybacterial infection affecting predominantly the oral mucosa of debilitated malnourished children or immunosuppressed HIV-seropositive subjects. It starts as necrotising gingivitis which progresses to necrotising periodontitis and subsequently to necrotising stomatitis. In order to prevent the progression of necrotising stomatitis to noma (cancrum oris), affected patients should be vigorously treated and may require admission to hospital. Healthcare personnel should therefore be familiar with the signs and symptoms of necrotising gingivitis/necrotising periodontitis, of their potential sequelae and of the need for immediate therapeutic intervention.

Noma (cancrum oris) in the South African context.

Noma (cancrum oris) is a destructive necrotising disease affecting orofacial tissues predominantly of malnourished young children. It is characterised by a rapid acute onset which usually starts in the mouth, spreads intra-orally destroying soft tissue and bone and progresses to perforate the facial skin, causing disfigurement. Polybacterial anaerobic infection is critical too, but is not alone sufficient for the initiation of noma. Cofactors, first and foremost malnutrition, but also systemic viral and bacterial infections are crucial to the development of noma. A patient with necrotising stomatitis or noma must be admitted to hospital for antibiotic treatment, fluid and electrolytes as well as nutritional supplementation and general supportive treatment. The epidemiology of noma in the South African population is unknown, and the clinicopathological features are poorly characterised. Although worldwide there is no evidence that HIV infection is a strong risk factor for noma, HIV infection may play a substantial role in the pathogenesis of noma in South Africa.

Oral mucosal immunity.

Oral keratinocytes and dendritic cells of the oral mucosa, through molecular pattern recognition receptors, distinguish between commensal and pathogenic microorganisms and mediate the generation of protective immunoinflammatory responses to potentially invading pathogens or mediate immune tolerance toward commensal microorganisms. Oral immune tolerance is the result either of lack of activation of T cells in response to immunogenic presentation of antigens or of suppression of activity of effector T cells by regulatory T cells. Secretory immunoglobulin A (sIgA) antibodies at oral mucosal sites contribute to oral immunity by limiting colonization of microorganisms and their invasion of the epithelium. Ig isotype class switching to IgA is either dependent on or independent of T helper cells and is facilitated by cytokines secreted by dendritic cells and monocytes.

Inflammation in the context of oral cancer.

The link between cancer and inflammation is specific transcription factors that once activated have the capacity to enhance expression of genes that are common to both the regulation and the production of mediators of inflammation, and also to the regulation of the survival and proliferation of cancer cells. Cellular pathways activated by chronic inflammation brought about by chronic infections, by immune-mediated diseases, or by dysregulated wound healing at sites of repetitive tissue injury, constitute risk factors for initial cell transformation and for cancer progression. In established cancers, the cancer cells induce development of an exaggerated inflammatory state in the stroma, which in turn promotes cancer growth, invasion and metastasis. Inflammatory cells of myeloid origin in the tumour-associated stroma, mediate suppression of immune responses against cancer cells, which suppression favours tumour growth. Oral submucous fibrosis, and to a lesser extent oral lichen planus are precancerous conditions in which immuno-inflammatory processes are implicated in their pathogenesis, and in their cancerous transformation, if it occurs. Although there is some evidence for an association between oral squamous cell carcinoma on the one hand and dento-gingival bacterial plaques and chronic periodontitis on the other hand, the role of inflammation as the sole cause of cancerous transformation in such cases is not proven. The purpose of this article is to elaborate on some of the more important relationships between oral cancer and inflammation, and to comment on the role of inflammation in the pathogenesis of oral squamous cell carcinoma.

Noma (cancrum oris): a report of a case in a young AIDS patient with a review of the pathogenesis.

Noma (cancrum oris) is a mutilating necrotising disease of the orofacial tissues. It affects predominantly debilitated malnourished children, in whom the necrotic process may cause severe damage to mid-facial structures. Its aetiopathogenesis is uncertain, but its course is fulminating, and without timely intervention the disease may be fatal. Antibiotic treatment during any stage of necrotising stomatitis and of its sequel noma can stop progression of the disease; therefore detection and treatment of early intraoral necrotising lesions whether necrotising gingivitis, necrotising periodontitis or necrotising stomatitis are critical in preventing noma. We present an extreme case of noma in a malnourished HIV-seropositive child. There was an acute necrotic process affecting both the maxilla and the mandible with denudation of bone, spontaneous exfoliation of teeth, necrotising fasciitis and myonecrosis which destroyed the lips and cheeks and extended to the infra-orbital margins. There was severe disfigurement and severe impairment of function. Noma is primarily an anaerobic bacterial infection with secondary ischaemia leading to osteonecrosis and mid-facial destruction.

Financial aspects of sentinel lymph node biopsy in early breast cancer.

AIM: At present, early breast cancer is treated with conservative surgery of the primary lesion (BCS) along with axillary staging by sentinel lymph node biopsy (SLNB). Although the scintigraphic method is standardized, its surgical application is different for patient compliance, work organization, costs, and diagnosis related group (DRG) reimbursements. METHODS: We compared four surgical protocols presently used in our region: (A) traditional BCS with axillary lymph node dissection (ALND); (B) BCS with SLNB and concomitant ALND for positive sentinel nodes (SN); (C) BCS and SLNB under local anaesthesia with subsequent ALND under general anaesthesia according to the SN result; (D) SLNB under local anaesthesia with subsequent BCS under local anaesthesia for negative SN, or ALND under general anaesthesia for positive SN. For each protocol, patient compliance, use of consumables, resources and time spent by various dedicated professionals, were analyzed. Furthermore, a detailed breakdown of 1-/2-day hospitalization costs was calculated using specific DRGs. RESULTS: We reported a mean costs variation that ranged from 1,634 to 2,221 Euros (protocols C and D). The number of procedures performed and the pathologists' results are the most significant variables affecting the rate of DRG reimbursements, that were the highest for protocol D and the lowest for protocol B. CONCLUSIONS: In our experience protocol C is the most suitable in terms of patient compliance, impact of surgical procedures, and work organization, and is granted by an appropriate DRG. We observed that a multidisciplinary approach enhances overall patient care and that a revaluation of DRG reimbursements is opportune.

Analysis of demographic data obtained from pathology records.

INTRODUCTION: Pathologists commonly analyse patient data obtained from pathology records. Such information is useful in that it might provide an indication of changing patterns of disease, or of the aetio-pathogenesis of a disease process, but such data is seldom standardised. AIM: To determine to what extent the lack of standardisation may influence the resultant data and the conclusions drawn. MATERIALS AND METHODS: Pathology reports of all cysts diagnosed from 1994 to 2004 were retrieved. The diagnosis and site of the cyst, and the age, gender and race of patient were analysed. Comparative data from 1958 to 1992 was obtained from the text "Cysts of the oral regions". The data from the different periods was statistically compared. Only the four most common cysts were included: radicular, dentigerous, odontogenic keratocyst and nasopalatine duct cysts. RESULTS: There was no difference in frequency and site of cysts or in age of patients. Statistically significant differences were found in the gender and race comparisons. CONCLUSION: Do the differences reflect a changing pattern of disease or are they due to changes in the demographics of the patient pool from which the surgical specimens were obtained? We favour the latter. Awareness of the fact that data from either survey is not reliable due to lack of standardisation is pertinent to avoid drawing fundamental conclusions from such data.

[Organizational model of the Cancer Institute of Romagna (I.R.S.T.) and the Romagna Cancer Network]. / Modello organizzativo dell'Istituto Tumori della Romagna (I.R.S.T.) e della Rete Oncologica Romagnola.

The quality of a treatment is strictly connected to research and technological development: to carry out competitive research, investments in advanced technologies are compulsory. To invest in research and new technologies for the diagnosis and the treatment of neoplasies at first level is compulsory as well and it also represents the most effective method to save resources. The AWR (wide area Romagna) is an health care network which is now treating approx. 9,000 cancer patients a year in a regional population of 1,095,205 residents in the provinces of Forli-Cesena, Ravenna and Rimini. I.R.S.T (The Cancer Institute of Romagna) is the "nucleus" of the oncologic network: it works as a Hub for some highly specialized activities and as a Spoke for other activities on behalf of the Local Health Authorities. I.R.S.T.'s Mission is focused on Translational Research, representing a structure fully integrated within the Regional Health System. In agreement with the AVR's Local Health Authorities and on their behalf I.R.S.T. manages all oncological research and clinical trials, in addition to facilitating innovative trials, which require particular organizational structures and technologies that are not generally available in the oncologic network.

Secretory cells in adenomatoid odontogenic tumour: tissue induction or metaplastic mineralisation?

OBJECTIVE: To undertake a detailed histological investigation of a large series of adenomatoid odontogenic tumours (AOT) to document the frequency and histomorphology of secretory cells which might indicate an inductive capacity. MATERIALS AND METHODS: Haematoxylin and eosin stained sections of 51 cases of AOT were reviewed. Selected cases were stained with periodic acid-schiff (PAS) and Congo red. RESULTS: In five cases, secretory structures with a circular arrangement of tall columnar cells secreting enameloid-like matrix material were identified. Such structures have only very rarely been identified in AOT and their frequency, distribution and morphology have not been adequately documented. CONCLUSIONS: We have documented the presence of tall secretory columnar cells, arranged in a circular configuration actively secreting enameloid-like material and believe that such an ordered arrangement of secretory cells is more likely a result of tissue induction rather than metaplasia. The origin of these secretory structures from the pseudo-ductular component is unlikely but cannot be ruled out.