Providing high-quality care remotely to patients with rare bone diseases during COVID-19 pandemic.

During the COVID-19 outbreak, the European Reference Network on Rare Bone Diseases (ERN BOND) coordination team and Italian rare bone diseases healthcare professionals created the "COVID-19 Helpline for Rare Bone Diseases" in an attempt to provide high-quality information and expertise on rare bone diseases remotely to patients and healthcare professionals. The present position statement describes the key characteristics of the Helpline initiative, along with the main aspects and topics that recurrently emerged as central for rare bone diseases patients and professionals. The main topics highlighted are general recommendations, pulmonary complications, drug treatment, trauma, pregnancy, children and elderly people, and patient associations role. The successful experience of the "COVID-19 Helpline for Rare Bone Diseases" launched in Italy could serve as a primer of gold-standard remote care for rare bone diseases for the other European countries and globally. Furthermore, similar COVID-19 helplines could be considered and applied for other rare diseases in order to implement remote patients' care.

Osteogenesis imperfecta: practical treatment guidelines.

Osteogenesis imperfecta (OI), an inherited connective tissue disorder of remarkable clinical variability, is caused by a quantitative or qualitative defect in collagen synthesis and is characterised by bone fragility. The number of fractures and deformities, and the age at which they begin greatly influence the prognosis and the achievement of walking and autonomy. A multidisciplinary team approach is essential for diagnosis, for communication with patient and parents, and to tailor treatment needs to the severity of the disease and the age of the patient. Three types of treatment are available: nonsurgical management (physical therapy, rehabilitation, bracing and splinting), surgery (intramedullary rod positioning, spinal and basilar impression surgery), and drugs to increase the strength of bone and decrease the number of fractures. An aggressive rehabilitative approach is indicated to optimise functional ability and walking capacity; appropriately timed surgery to insert intramedullary rods provides improved function of extremities. Despite a high rate of complications, intramedullary telescopic roding has proven to be the most successful method for preventing and correcting fractures and deformities of long bones, improving walking capability and leading to successful rehabilitation of even severely affected patients. Surgery may be required in patients with progressive spinal deformity and in those with symptomatic basilar impression. Hearing function, dentinogenesis imperfecta, cardiac and respiratory function, and neurological changes must be monitored. The causal defect of the disease cannot be corrected with medical treatment and, currently, only symptomatic therapy is available. In recent years growth hormone (GH) and bisphosphonate agents have been used in OI therapy. GH is beneficial in patients with moderate forms of OI, showing a positive effect on bone turnover, bone mineral density and height velocity rate. Bisphosphonates have proved beneficial in children with severe OI, increasing bone mineral density and reducing the fracture rate and pain with no adverse effects reported. These data require confirmation in double-blind controlled studies; however, bisphosphonates have markedly improved morbidity in patients with OI. Future developments in genetic therapy may be directed towards either replacing cells carrying the mutant gene with normal cells or silencing the mutant allele using antisense suppression therapy, thus transforming a biochemically severe form of OI into a mild form.

Epirubicin treatment of advanced breast carcinoma with the weekly low-dose regimen.

Authors describe the results obtained with weekly low-dose (20 or 30 mg/total) of intravenous bolus epirubicin, used as second line chemotherapy, after CMF, in 29 advanced breast carcinoma patients. 29% objective response rate (1 complete + 6 partial responses) has been observed in 24 evaluable patients, with median response duration of 4 months (range 1-7+). The discrete response rate and the minimal incidence of side effects call for further studies and more extensive evaluation of epirubicin given alone or in combination through this new treatment schedule.

Confirmed activity of FAM polychemotherapy in advanced gastric carcinoma.

During a 3-year period at our hospital, 54 consecutively observed patients with parametric, locally advanced, metastatic gastric carcinoma were treated with fluorouracil + adriamycin + mitomycin C. Of 47 evaluable patients, 44.6% had an objective response (complete + partial response) and 29.7% had stabilized disease. The median duration of response was 7.5 months. The median survival was 8.9 months for all patients. In particular, the survival of responders (greater than 12 months) and of patients with stabilized disease (8.6 months) was significantly longer than that of patients with progressive disease (4.5 months). Toxicity was limited and reversible, which allowed treatment also of patients in poor general condition (PS 3-4 of the Zubrod scale).

Cardiac toxicity of 5-fluorouracil: a study on 1083 patients.

The possible onset of cardiotoxic manifestations during chemotherapy with 5-fluorouracil (5-FU) was evaluated in 1083 patients treated with the drug for various kinds of neoplasm. We recognized 17 cases of 5-FU cardiopathy (usually anginous crises but also myocardial infarction). The comprehensive incidence was 1.6%, with a significantly greater risk (4.5% vs 1.1%) for patients with a positive anamnesis of previous cardiopathy. On the contrary, age and combination with other antiblastic drugs had no affect on the appearance of cardiopathy. We conclude that 5-FU cardiopathy, although rare, has to be taken into account in oncologic practice, chiefly in those patients already affected with cardiac diseases.

Chemotherapy of soft tissue sarcomas.

The medical treatment of advanced soft tissue sarcomas in adults is reviewed. Response rates of 40--50% are obtainable after various polychemotherapies, mainly containing doxorubicin and dacarbazine. Response to secondary treatment is very poor and indicates the need for further clinical research in these infrequent malignant tumors.

Levamisole in cancer treatment: modifications in time of cellular immunity. (Preliminary report).

Some preliminary observations are reported on a restricted case-list of patients with neoplastic disease in remission, after suitable treatment (surgical and/or radiant and/or antiblastic), treated with levamisole. The results obtained, even if preliminary, stress the close relationship between the immunorestorative effect and the length of the administration. Besides, the restoration of the secondary delayed immunity turned out promptly, in comparison with the primary delayed immunity. Very scanty the side effects observed.

[Importance of the analysis of the carcinoembryonic antigen in clinical oncology]. / Importanza del dosaggio dell'antigene carcino-embrionario in oncologia clinica.

330 patients (126 with gastric neoplasms, 204 with large bowel carcinoma) were submitted to serial assays to evaluate the possible relations between C.E.A. levels, pathologic stage and histologictype of the neoplasm and to define the usefulness of the C.E.A. test in monitoring the followup of the patients with gastrointestinal neoplasms. From our experience it ensues that C.E.A. test positivity (C.E.A. greater than or equal to 5 ng/ml, according to the method employed) is higher in colon neoplasms in comparison with gastric neoplasms, in the adenocarcinomas compared with the anaplastic forms. Besides, the study of the relationship with the pathologic stage points out the scanty usefulness of the C.E.A. test in the early diagnosis of gastroenteric neoplasms (Dukes A-B-C1 = 29.2%; CH stage = 88.1%). The use of C.E.A. test during the follow up seemed us of fundamental importance. We observed that: a) after radical surgery, 72% of the patients showed a normalization of C.E.A. values; b) there is a significant relationship between clinical course and C.E.A. as it can predict, sometimes several months earlier, the occurrence of relapses and metastases; c) there is also a close relationship (P less than 0.001) between the modifications of the antigen under chemotherapy and the clinical response. At present, C.E.A. seems to play, above all, fundamental role in choosing a correct treatment after radical surgery or in modifying the chemotherapeutic treatment in non surgical cases or in non radically resected patients.

Clinical usefulness of CEA assay.

CEA is a normal constituent of fetal cells, which can reappear in entodermally-derived neoplasms, following a de-repression process. In order to evaluate the correlation between CEA serum levels, pathological stage and histological type of tumour, and to define the usefulness of CEA in monitoring the patients with gastroenteric neoplasms, 177 patients (62 with gastric heteroplasia and 115 with large bowel carcinoma) were tested for CEA; 83 patients had pre-surgical CEA tests. It was observed that CEA positivity (serum levels greater than or equal to 5 ng/ml, employing the technique here outlined), is higher in colonic than in gastric neoplasms, and in adenocarcinomas in comparison with undifferentiated forms, moreover depending on the pathologic stage. 108 patients were tested for CEA several times and a correlation between CEA variations and clinical evolution was observed. This investigation bears out the importance to monitor the patients with gastrointestinal neoplasms with CEA test, before and after surgery, to evaluate the usefulness of surgery and, when necessary, chemotherapy and, eventually, to adopt more suitable chemotherapeutic modalities.

Correlation between clinical course and CEA levels during chemotherapy.

In order to evaluate the correlation between clinical progress and CEA levels in gastroenteric tumours, particularly during chemotherapeutic treatment, CEA assay was performed on 330 patients (126 with gastric neoplasms, 204 with large bowel carcinoma). 175 out of these had a pre-operative assay. Moreover CEA test positivity (CEA larger than or equal to 5 ng/ml according to the technique employed by us) is higher in colon neoplasms compared with gastric neoplasms and in adenocarcinomas in comparison with undifferentiated forms; besides it depends on the pathologic stage. In colon tumours CEA test showed a higher positivity for left than for right forms (66.6% versus 38%). 240 patients were followed up with repeated CEA assays: the following observations were made: a - After radical surgery 72% of the patients shows normalized CEA values. b - In 198 patients who underwent radical surgery, not requiring chemotherapy, there was a close correlation between CEA levels and clinical evolution in 98% of the cases. c - 60 out of 68 patients (88%) submitted to chemotherapy for advanced neoplasms show a close correlation between CEA response to the chemotherapy and clinical response (p less than 0.001). These investigations stress, above all, the importance of CEA test to monitor the treatments performed (surgical and chemotherapeutic) and to adopt, eventually, more effective chemotherapeutic modalities.

Immunological investigation and immunotherapy approaches in cancer patients.

The Authors report the preliminary results of a two-step far-reaching investigation carried out on cancer patients to study: 1) the immune conditions of the patients and establish, by a thorough immune monitoring, employing tests of humoral immunity (tetanus toxoid response), of delayed immunity (BCG test, PHA-lymphocyte blastogenesis, MIF release, skin window) and macrophage immunity (skin window), the chemotherapy effects on the immune conditions and the most suitable time to carry out immunotherapy; 2) the immunotherapeutic results which can be obtained with three different immunogens (BCG, C. parvum and ribonucleotides). The results obtained in the first part of the investigations pointed out the usefulness of the tests adopted to follow up the evolution of the immunological reactivity in patients submitted to chemotherapy, while the results of the immunotherapeutic trial show a preliminary character and, at present, do not allow definitive conclusions. Carefully planned and randomized studies are at present under way to establish, more thoroughly, the optimal modalities and the real possibilities of the immunotherapy performed with C. parvum and ribonucleotides in cancer patients.