Transmission mode associated with coronavirus disease 2019: a review.

OBJECTIVE: In late December 2019 in Wuhan (China), Health Commission reported a cluster of pneumonia cases of unknown etiology, subsequently isolated and named Severe Acute Respiratory Syndrome (SARS) Coronavirus 2 (CoV-2). In this review, the main transmission routes and causes of mortality associated with COVID-19 were investigated. MATERIAL AND METHODS: A review was carried out to recognize relevant research available until 10 April 2020. RESULTS: The main transmission routes of COVID-19 have been the following: animal to human and human-to-human pathways, namely: respiratory transmission; oro-fecal transmission; air, surface-human transmission. Transmission from asymptomatic persons, healthcare transmission, and interfamily transmission have been well documented. CONCLUSIONS: SARS-CoV-2 possesses powerful pathogenicity and transmissibility. It is presumed to spread primarily via respiratory droplets and close contact. The most probable transmission pathway is definitely the inter-human one. Asymptomatic patients seem to play a crucial role in spreading the infection. Because of COVID-19 infection pandemic potential, careful surveillance is essential to monitor its future host adaptation, viral evolution, infectivity, transmissibility, and pathogenicity in order to gain an effective vaccine and flock immunity and reduce mortality as soon and as much as it is possible.

Ozone therapy in 65 patients with fibromyalgia: an effective therapy.

OBJECTIVE: Fibromyalgia is a chronic disorder with a very complex symptomatology. Although generalized severe pain is considered to be the cardinal symptom of the disease, many other associated symptoms, especially non-restorative sleep, chronic fatigue, anxiety, and depressive symptoms also play a relevant role in the degree of disability characteristic of the disease. Ozone therapy, which is used to treat a wide range of diseases and seems to be particularly useful in the treatment of many chronic diseases, is thought to act by exerting a mild, transient, and controlled oxidative stress that promotes an up-regulation of the antioxidant system and a modulation of the immune system. According to these mechanisms of action, it was hypothesized that ozone therapy could be useful in fibromyalgia management, where the employed therapies are very often ineffective. PATIENTS AND METHODS: Sixty-five patients with fibromyalgia, according to the definition of the American College of Rheumatology (Arthritis Rheum 1990; 33: 160-172), were treated at the MEDE Clinic (Sacile, Pordenone, Italy) from February 2016 to October 2018. Females were 55 and males were 10; age ranged from 30 to 72 years, and the time from fibromyalgia diagnosis ranged from 0.5 to 33 years. Treatment was made by autohemotransfusion in 55 patients and by ozone rectal insufflations in 10 patients, according to SIOOT (Scientific Society of Oxygen Ozone Therapy) protocols, twice a week for one month and then twice a month as maintenance therapy. RESULTS: We found a significative improvement (>50% of symptoms) in 45 patients (70%). No patient reported important side effects. In conclusion, at our knowledge, this is the largest study of patients with fibromyalgia treated with ozone therapy reported in the literature and it demonstrates that the ozone therapy is an effective treatment for fibromyalgia patients without significant side effects. CONCLUSIONS: At the moment, ozone therapy seems a treatment that, also because without any side effect, is possible to be proposed to patients with fibromyalgia that are not obtaining adequate results from other available treatments and it can be considered as complementary/integrative medicine.

Oxygen-ozone therapy as support and palliative therapy in 50 cancer patients with fatigue - A short report.

OBJECTIVE: Fatigue may be cause by all cancer treatments, maybe because the tissue damage or the build-up of dead cells derived products. PATIENTS AND METHODS: At the Mede Clinic in Sacile, Pordenone, Italy, from February 2016 to May 2018 we studied 50 patients with cancer and fatigue (15 with breast cancer, 12 with lung cancer, 11 with colon cancer, 5 with renal cancer, 3 with prostate cancer, 2 with melanoma and 2 hepatocellular carcinoma). Patients were treated with Auto Hemotransfusion (GAE) according to the SIOOT (Scientific Society of Oxygen Ozone Therapy) protocols, two times a week for one month and then twice monthly as maintenance therapy. RESULTS: Nineteen of them were undergoing neoplastic treatment, 10 had already ended the cancer therapy and 21 were in a palliative setting. The Fatigue Severity Scale was used to assess the extent of fatigue in patients, in order to estimate the severity of the symptom with a score from 1 to 7. No side effects were found, and 35 patients (70%) achieved a significant improvement (> 50%) of the symptoms. CONCLUSIONS: Our preliminary data demonstrate that ozone therapy is a valid supportive therapy for fatigue in cancer patients, both during cancer therapy and in a palliative setting with no significant side effects.

Rational selection of predictive pharmacogenomics test for the Fluoropyrimidine/Oxaliplatin based therapy.

OBJECTIVE: Both Fluoropyrimidine and Oxaliplatin (FluOx) are the most common anticancer drugs used to treat colorectal, ovarian, and gastrointestinal cancers. Nevertheless, the efficacy of FluOx-based therapy is often compromised by the severe risk of neurotoxicity, cardiotoxicity, and gastrointestinal toxicity. Stratification of patients for their individual response to drugs is a promising approach for cancer treatment and cost-effectiveness. Here we evaluate the most recent findings on the most appropriate gene variants related to the toxicity in patients receiving FluOx chemotherapy. MATERIALS AND METHODS: A systematic literature search of the MEDLINE, EMBASE, and Cochrane databases was conducted to identify all clinical studies of any association between DPYD and 5-FU correlated to allelic status of 6 validated polymorphisms in five genes Dihydropyrimidine Dehydrogenase (DPYD), Thymidylate Synthase (TYMS), Glutathione S-Transferase (GSTP1), and DNA-repair genes (ERCC2 and XRCC1). RESULTS: The stratification of the patients into three genotype profiles group, who are most likely responders to FluOx treatments, provide informations about toxicity and/or resistance before starting therapy. Also, early evaluation cost of panel testing proposed is averaged about €100,00 per sample. The evaluation costs of genotyping before starting treatment could be a good cost-effectiveness strategy. CONCLUSIONS: Based on the individual genomic profile, the oncologists will have new possibilities, based on the individual genetic profile, to make treatment decisions for their patients and to redefine scheduling and dosage of FluOx-based therapy.

Head and neck cancer survivors patients and late effects related to oncologic treatment: update of literature.

Cancer survivorship represents a new challenge in the third Millennium. In Europe the number of cancer survivors was estimated to be 17,8 million in 2008 and this number is growing. Recent improvements in cancer survival are largely due to earlier diagnosis and advancements in treatment. Despite having favorable effects on cancer survival, radiation therapy, surgery treatment and combination chemotherapy regimens can also cause long-term organ damage and functional disabilities. In this paper we review the most important aspects of long-term toxicities in otolaryngology cancer survivors patients.

Feasibility of intraperitoneal Trastuzumab treatment in a patient with peritoneal carcinomatosis from gastric cancer.

OBJECTIVES: This case report evaluates the feasibility and efficacy of intraperitoneal (IP) trastuzumab administration in gastric cancer (GC) patients with peritoneal carcinomatoses. METHODS: Peritoneal metastasis is a common sign of advanced tumor stage, tumor progression or disease recurrence in patients with GC. Recently, the role of HER2 overexpression in GC, occurring in about 20% of cases, is correlated with a worse prognosis. We report the case of 61-years old female, admitted to our Hospital after curative surgery for GC with over-expression of HER2. Seven months after the start of first line chemotherapy treatment a pleuro-peritoneal disease progression occurred, documented by cytological exam; according to HER2 status, we decided to treat the patient with IP trastuzumab administration. RESULTS: Between September and October 2012, the patient (ECOG performance status was 0), underwent to 6 cycles of IP trastuzumab. Trastuzumab was administered weekly at a dose of 150 mg for each cycle after paracentesis. The safety was good, no local complications (e.g. abdominal pain, peritonitis) occurred. The clinical revaluation evidenced a stable peritoneal disease. CONCLUSIONS: To our knowledge this is the first report on Trastuzumab use to treat IP metastases from GC, with acceptable toxicity and local disease control.

Lung cancer in HIV positive patients: the GICAT experience.

PURPOSE: AIDS incidence and mortality have decreased since the introduction of highly active antiretroviral therapy (HAART) into clinical practice. HIV-related malignancies, namely Kaposi's sarcoma and Non-Hodgkin's lymphoma, have decreased, whereas non-AIDS defining tumors have been increasing. Our aim was to study the impact of HAART on natural history of lung cancer in HIV-positive patients, comparing patients with HIV-lung cancer treated in the pre-HAART era versus the HAART era. PATIENTS AND METHODS: We collected 68 patients with HIV-lung cancer diagnosed from 1986 to 2003. Pre-HAART era included 34 patients who did not receive HAART, whereas the HAART era included 34 patients diagnosed after January 1997 who received HAART. RESULTS: At diagnosis Performance Status (PS) was significantly different, patients with PS ≥ 2 were 44% in the pre-HAART era, versus 29% in the post-HAART era, p = 0.02. The 79.4% of patients in the post-HAART era received chemotherapy alone or with radiotherapy versus 47% in the pre-HAART era, p = 0.04. Cancer was the leading cause of death for both groups, with 29 (85.3%) and 21 (61.8%) patients in the pre- and post-HAART settings, respectively. The median overall survival (OS) was 3.8 months for the pre-HAART population vs. 7 months for the post-HAART patients, p = 0.01. CONCLUSIONS: HIV-lung cancer patients have a longer overall survival in the post-HAART era versus the pre-HAART era, due to a not detrimental effect of chemotherapy and positive effect of HAART. Lung cancer is the leading cause of death, showing that treatment of the cancer is the most important target now to improve their outcome.

Effort myocardial ischemia during chemotherapy with 5-fluorouracil: an underestimated risk.

BACKGROUND: Effort-induced myocardial ischemia (EMI) has been seldom described. Aims of our study were (A) to evaluate the prevalence of EMI during long-lasting 5-FU infusion; (B) to identify possible risk factors of EMI during 5-FU infusion. PATIENTS AND METHODS: For the purpose (A), we prospectively evaluated a group of patients undergoing in-hospital continuous infusion (c.i.) of 5-FU. Patients with rest ischemia were excluded. Among 358 consecutive patients, 21 (5.9%) had rest ischemia; 109 could not perform a stress test. The remaining 228 patients underwent a treadmill stress test (TST) after >46 h of 5-FU infusion. For the purpose (B), we compared the characteristics of patients with EMI (including 3 previously described in a 2001 paper) with those without EMI. RESULTS: Among 228 patients, 16 (6.9%) had EMI. These 16 had a second TST after stopping 5-FU: in 14, it was negative, 2 patients with coronary artery disease had milder ischemia. The whole group of 231 (including 3 described in a previous paper) patients undergoing TST included 148 males and 83 females, with mean age of 57.5. Cardiovascular risk factors were present in 178 of them. Eight patients had ischemic heart disease. Among 19 patients with EMI, 7 had angina, 12 silent ischemia. ST segment at ECG was elevated in 10 patients, depressed in 9. Comparing the group with toxicity and the one without, the only significant difference was the complaint of atypical symptoms at rest before the TST. No difference was observed as regards: chemotherapy schedule (chronic c.i. in 49, 5 days in 178, FOLFOX type in 12), coronary risk factors or heart disease. CONCLUSIONS: EMI is as frequent as rest ischemia during 5-FU infusion. Patients undergoing 5-FU continuous infusions should be adviced to avoid unusual efforts, to refer any cardiac symptom, and should be investigated for EMI.

Treatment of 741 Italian patients with chronic fatigue syndrome.

BACKGROUND: Chronic Fatigue Syndrome (CFS) is a distinctive syndrome characterized by specific symptoms cluster. CFS mostly affects women and often results in severe functional limitation. Its prevalence varies from 0.4 to 2.5% in the general population. In our prior studies on the clinical features of 205 CFS patients we founded immunological and brain abnormalities. In this paper we illustrate our caseload on CFS treatment. PATIENTS AND METHODS: From January 2000 to December 2005, we evaluated all the patients admitted at the CFS Unit of the Aviano National Cancer Institute, for staging procedures and treatments. Patients not meeting the Fukuda diagnostic criteria were excluded. RESULTS: 250 male and 491 female (median age 35.5 and 39.3 years, respectively) were enrolled and treated for CFS. As expected, CFS resulted from previous infectious disease in all patients. Female patients showed to be more affected by symptoms than male patients. The treatment schedules followed by the patients included nutritional supplements alone, corticosteroids, antidepressant/sedative drugs, and antiviral/immunoglobulin drugs. Antiviral/ immunoglobulin drugs achieved the best response (15.3% positive responses vs. 8.3% negative responses; OR 0.44, CI 0.26-0.74, p = 0.002). The carrying out of 4 or more treatments showed a protective effect (OR 0.46, CI 0.28-0.77, p = 0.003). This finding was confirmed in the multivariate analysis, adjusted by type of drugs (OR 0.49, CI 0.28-0.84, p = 0.009) and number of treatments carried out (OR 0.51, CI 0.30-0.86, p = 0.01); these two variables were independent. CONCLUSIONS: These findings show that the antiviral/immunoglobulin approach has a longer positive disease free survival in comparison with other approaches. However, CSF still remains a difficult disease to be effectively treated.

Kaposi' s sarcoma in HIV-positive patients: the state of art in the HAART-era.

Kaposi's sarcoma (KS) is a multicentric angioproliferative cancer of endothelial origin typically occurring in the context of immunodeficiency, i.e. coinfection with Human Immonodeficiency Virus (HIV) or transplantation. The incidence of KS has dramatically decreased in both US and Europe in the Highly Active Antiretroviral Therapy (HAART) era. However, KS remains the second most frequent tumor in HIV-infected patients worldwide and it has become the most common cancer in Sub-Saharan Africa. In 1994, Yuan Chang et al discovered a novel γ-herpesvirus in biopsy specimens of human KS. Epidemiologic studies showed that KS-associated herpesvirus (KSHV) or human herpesvirus-8 (HHV-8) was the etiological agent associated with all subtypes of KS. KS has a variable clinical course ranging from very indolent forms to a rapidly progressive disease. HAART represents the first treatment step for slowly progressive disease. Chemotherapy (CT) plus HAART is indicated for visceral and/or rapidly progressive disease. The current understanding of KS as a convergence of immune evasion, oncogenesis, inflammation and angiogenesis has prompted investigators to develop target therapy, based on anti-angiogenic agents as well as metalloproteinase and cytokine signaling pathway inhibitors. These drugs may represent effective strategies for patients with AIDS-associated KS, which progress despite chemotherapy and/or HAART. In this review, we focus on the current state of knowledge on KSHV epidemiology, pathogenesis and therapeutic options.

Long term cryopreservation in 5% DMSO maintains unchanged CD34(+) cells viability and allows satisfactory hematological engraftment after peripheral blood stem cell transplantation.

Peripheral blood stem cell cryopreservation is associated with cell damage and decreased viability. We evaluated the impact of up to 10 years of cryopreservation (5% DMSO) on viability of CD34(+) cells utilizing graft samples of consecutive patients (2002-2012) with different malignancies who underwent stem cell collection and transplantation. Viability of CD34(+) cells from oncohaematological patients measured after 5 weeks (97·2 ± 0·6%) or after 9-10 years of cryopreservation (95·9 ± 0·5%) was unaffected. Haemoglobin, granulocyte and platelet recovery after transplantation of long-term cryopreserved grafts occurred within 8-13 days. CD34(+) stem cells can be safely stored up to 9-10 years, without affecting cell viability and clinical effectiveness.

Antiblastic treatment of haematological malignancies during pregnancy: a crucial decision.

Antiblastic treatment of hematological malignancies during pregnancy poses a number of issues related to the curability of the maternal disease, the need of a prompt treatment and the potential toxicity of chemotherapy for the fetus. Here we report the results of a systematic literature search about the management of the most frequent hematological malignancies that may occur during pregnancy, focusing on specific issues related to gestational age at diagnosis, fetal toxicity and efficacy on the maternal side. The standard approach in non-pregnant women is illustrated as reference.

Antiblastic treatment, for solid tumors, during pregnancy: a crucial decision.

Cancer is the second leading cause of death during the reproductive years complicating between 0.02 percent and 0.1 percent of pregnancies. The incidence is expected to rise with the increase in age of childbearing. The most common types of pregnancy-associated cancers are: cervical cancer, breast cancer, malignant melanoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma and ovarian cancer. The relatively rare occurrence of pregnancy-associated cancer precludes conducting large, prospective studies to examine diagnostic, management and outcome issues. The treatment of pregnancy-associated cancer is complex since it may be associated with adverse fatal effects. In pregnant patients diagnosed with cancer during the first trimester, treatment with multidrug anti-cancer chemotherapy is associated with an increased risk of congenital malformations, spontaneous abortions or fetal death, and therefore, should follow a strong recommendation for pregnancy termination. Second and third trimester exposure is not associated with teratogenic effect but increases the risk of intrauterine growth retardation and low birth weight. There are no sufficient data regarding the teratogenicity of most cytotoxic drugs. Almost all chemotherapeutic agents were found to be teratogenic in animals and for some drugs only experimental data exist. Moreover, no pharmacokinetic studies have been conducted in pregnant women receiving chemotherapy in order to understand whether pregnant women should be treated with different doses of chemotherapy. This article reviews the available data regarding the different aspects of the treatment of cancer during pregnancy.

Target therapies in lung cancer.

Targeting intracellular signaling molecules is an attractive approach for treatment of malignancies. In particular lung cancer has reached a plateau regarding overall survival, and target therapies could offer the possibility to improve patients' outcome beyond cytotoxic activity. The goal for target therapies is to identify agents that target tumor-specific molecules, thus sparing normal tissues; those molecules are called biomarkers, and their identification is recommended because it has a predictive value, for example, provides information on outcome with regard to a specific treatment. The increased specificity should lead to decreased toxicity and better activity. Herein we provide an update of the main target therapies in development or already available for the treatment of nonsmall cell lung cancer.

Safety and efficacy of radiotherapy treatment in elderly patients with localized prostate cancer: a retrospective analysis.

The purpose of this study was to evaluate the feasibility and the activity of radiotherapy treatment in patients aged ≥75 with prostate cancer (PC). From January 2000 to December 2007, 107 consecutive patients aged ≥75 years received radiotherapy with radical intent for PC. Eighty-one patients received radiotherapy in combination with a 6 months androgen suppression therapy. Variables considered were age, stage, co-morbidities according to the adult co-morbidity evaluation index (ACE-27) and performance status (PS). The median age was 79.1 years (range 76-87). The 23.4% of patients showed no co-morbidities, while the 46.7% had mild, 23.4% moderate, and 6.5% severe co-morbidities, respectively. All patients completed the planned radiation treatment. At a median follow-up of 37.8 months, the 5-year overall survival rate was 78%. There was a better survival for patients with no or mild co-morbidities (p<0.0001) and a good PS (p=0.009). The actuarial disease-free survival at 60 months was 75.8%. Difference in acute and late toxicity rate was detected between ACE-27 classes for diarrhea and marginally for urinary toxicity, but no difference was detected for different age. We conclude that compliance with radiotherapy is good and rate of toxicity is acceptable in elderly patients. Increasing severity of co-morbidity may sufficiently shorten remaining life expectancy to cancel gains with radical radiotherapy. Further prospective trials are needed to confirm these results.

FOLFOX2 in the treatment of advanced colorectal cancer: a comparison between elderly and middle aged patients.

The effectiveness of chemotherapy in elderly patients is still a matter of debate. We analyzed the toxicity and efficacy of the original FOLFOX2 regimen in middle aged and elderly patients affected by metastatic colorectal cancer. Consecutive patients with metastatic CRC and measurable disease were eligible. Seventy-eight partially pretreated patients were enrolled: 58 patients were defined as middle aged (<70 years) and 20 were elderly patients (>70 years). Elderly patients in comparison to middle-aged patients in a higher percentage were males. No significant differences were found in hematological and non-hematological toxicity between the two groups. No significant differences were found in the response rates, time to progression (5.9 vs. 6.0 months respectively), or median overall survival (20.9 and 21.8 months, respectively) between middle aged and elderly patients. The FOLFOX2 regimen provides equivalent feasibility, efficacy, and survival gain in middle-aged and in elderly patients with metastatic CRC.