Oxygen-ozone autohemotherapy in breast cancer patients suffering from fatigue and musculoskeletal pain upon aromatase inhibitors treatment: a case-series study.

OBJECTIVE: In patients with breast cancer and positive hormone receptors, aromatase inhibitors are effective in reducing the risk of recurrences and are active in progressing the disease in this setting. On the other hand, fatigue and painful musculoskeletal side effects can significantly reduce treatment compliance. With no further treatment options to control these symptoms, non-pharmaceutical interventions, such as oxygen-ozone therapy, may play a role in managing rheumatologic symptomatology inasmuch. We have previously reported evidence on the effectiveness of oxygen-ozone in the treatment of pain and fatigue in chronic fatigue syndrome and fibromyalgia patients and in oncological patients as well. PATIENTS AND METHODS: In this study, we reported 6 cases of patients (mean age 64 yrs, all Caucasian females) with breast cancer upon treatment with anastrozole (Arimidex®), suffering from musculoskeletal pain, weakness and fatigue, and therefore treated with oxygen-ozone major autohemotherapy according to the Italian Scientific Society of Oxygen Ozone Therapy (SIOOT) protocol. Pain was measured with a 10-item Numerical Rating Scale (NRS) and fatigue with a 7-item Fatigue Scoring Scale (FSS). RESULTS: A reduction of at least 66% of pain (from 9.43 ±0.54 SD to 2.36 ±1.32 SD, p<0.001) and 66.26% of fatigue were obtained for all the cases. Pain and fatigue disappeared within one month from ozone therapy, and a healthy painless state lasted for many months following the oxygen-ozone therapy. CONCLUSIONS: The oxygen-ozone therapy is a sound opportunity for breast cancer patients to reduce anti-aromatase-induced pain, fatigue, and musculoskeletal symptoms.

Lung cancer and COVID-19: problems and perspectives.

COVID-19 pandemic generated concerns about the healthcare of patients with cancer, not simply because of the formidable impact of COVID-19 patients in the public healthcare system, but also due to the overlapping pathognomonic signs of many forms of lung cancer with lung injuries associated with COVID-19. This report tries to shed light on the issue. We evaluated the great concern of people suffering from lung cancer and also infected with SARS-CoV-2 by discussing evidence and data from current literature. Lung cancer in Italy has represented more than 1 case/4 (27%) in the latest ten years and nevertheless, even due to the concurrence of many complex interplays between COVID-19 and cancer even at the immune level, a consensus protocol and expert guidelines to diagnose and treat lung cancer upon SARS-CoV-2 infection are yet lacking. New insights and consensus panels should be therefore proposed, even at the simplistic level about if priority must be either given to COVID-19 or to cancer therapy.

Fibromyalgia treated with oxygen-ozone auto-haemotherapy (O2-O3-AHT): a case study on 200 patients with a modified 10-PI-NRS evaluation.

OBJECTIVE: Fibromyalgia (FM) is a concerning chronic disease showing as widespread pain, muscle stiffness, sleep disturbances, chronic fatigue, and depressed mood, for which no sound therapy is yet available to date. In this article we assessed a wider patients' cohort the efficacy of oxygen-ozone autohemotherapy (O2-O3-AHT) previously reported. PATIENTS AND METHODS: A number of 200 FM-patients accessed the study and were treated with 3-4 runs of O2-O3-AHT, following their signed consent. A modified 10 points-PI-NRS were used to evaluate pain intensity before and after the conclusion of the complete ozone-treatment cycle (1 month). Kruskall-Wallis' test and other statistics were used at p<0.05 level of significance. RESULTS: A quite complete rehabilitation of the musculoskeletal function and of the overall arthralgia was observed in 76% of the patients at one month of follow-up. The number of patients having a reduction in the PI-NRS score from 10 (the maximal observed) to 3 (including 10-1 and 10-2) following only two runs of O2-O3-AHT was 23.5%, whereas only 17.5% did not show any significant improvement (ΔPI-NRS = 0 or 1), so assessing that the efficacy of O2-O3-AHT, independently from ages, encompassed at least 41% in a moderate way and 64.5% of the treated patients, as a whole. CONCLUSIONS: Oxygen-ozone autohemotherapy represents a formidable therapeutic approach for FM, deserving further studies to be made in order to fully elucidate ozone effect of this pathology.

Sjögren syndrome successfully treated with oxygen-ozone auto-hemotherapy (O2-O3-AHT). a case report.

OBJECTIVE: Sjögren syndrome (SS) is an autoimmune disorder, affecting about 16,000 individuals in Italy, yet lacking a standardized therapy protocol and a plain inclusion in the reimbursed healthcare services. This raises many controversial issues about how managing the SS patient, to relief pain and discomfort and improve patients' health and social life. The ozone therapy resulted successful in previous reports, and therefore, it was used in this case report. CASE PRESENTATION: A 69-years old female outpatient, showing positivity to Schirmer's test, was previously diagnosed as a primary Sjögren syndrome, who later developed an autoimmune thyroiditis and showed the presence of rheumatoid factors. The patient suffered from a marked ocular dryness, subsequently to a purported endothelitis, alongside with fatigue and pain. Laboratory tests showed a positive ANA 1:320 in a speckled pattern with negative anti-SSA and anti-SSB tests. From December 2020 to January 2021 she underwent 2 routes of three sessions of oxygen-ozone autohemotherapy (O2-O3 AHT), as described below and improved, with only 2 sessions, her symptomatology and clinical outcome, as ocular dryness, fatigue and pain, rapidly disappeared. CONCLUSIONS: The use of ozone in the therapy of SS is a straightforward, affordable and feasible approach to treat primary Sjögren syndrome without significant side effects.

Fatigue in post-acute sequelae of SARS-CoV2 (PASC) treated with oxygen-ozone autohemotherapy - preliminary results on 100 patients.

OBJECTIVE: Post-acute sequelae of SARS-CoV2 infection (PASC) are a novel terminology used to describe post-COVID persistent symptoms, mimicking somehow the previously described chronic fatigue syndrome (CFS). In this manuscript, we evaluated a therapeutical approach to address PASC-derived fatigue in a cohort of past-COVID-19 positive patients. PATIENTS AND METHODS: A number of 100 patients, previously diagnosed as COVID-19 positive subjects and meeting our eligibility criteria, was diagnosed having PASC-related fatigue. They were recruited in the study and treated with oxygen-ozone autohemotherapy (O2-O3-AHT), according to the SIOOT protocol. Patients' response to O2-O3-AHT and changes in fatigue were measured with the 7-scoring Fatigue Severity Scale (FSS), according to previously published protocols. RESULTS: Statistics assessed that the effects of O2-O3-AHT on fatigue reduced PASC symptoms by 67%, as a mean, in all the investigated cohort of patients (H = 148.4786 p < 0.0001) (Figure 1). Patients following O2-O3-AHT therapy, quite completely recovered for PASC-associated fatigue, a quote amounting to about two fifths (around 40%) of the whole cohort undergoing ozone treatment and despite most of patients were female subjects, the effect was not influenced by sex distribution (H = 0.7353, p = 0.39117). CONCLUSIONS: Ozone therapy is able to recover normal functionality and to relief pain and discomfort in the form of PASC-associated fatigue in at least 67% of patients suffering from post-COVID sequelae, aside from sex and age distribution.

Ozone Exerts Cytoprotective and Anti-Inflammatory Effects in Cardiomyocytes and Skin Fibroblasts after Incubation with Doxorubicin.

INTRODUCTION: Skin reactions and cardiotoxicity are one of the most common side effects of doxorubicin in cancer patients. The main mechanisms based on the etiopathogenesis of these reactions are mediated by the overproduction of proinflammatory cytokines, metalloproteases, and the disruption of mitochondrial homeostasis. Ozone therapy demonstrated anti-inflammatory effects in several preclinical and clinical studies. The aim of this research is based on the evaluation of cardioprotective and dermatoprotective effects of ozone during incubation with doxorubicin, giving preliminary evidences for further studies in the field of cardio-oncology. METHODS: Human skin fibroblast cells and human fetal cardiomyocytes were exposed to doxorubicin at subclinical concentration (100 nM) alone or combined with ozone concentrated from 10 up to 50 µg/mL. Cell viability and multiple anti-inflammatory studies were performed in both cell lines, with particular attention on the quantification of interleukins, leukotriene B4, NF-κB, and Nrf2 expressions during treatments. RESULTS: Ozone decreased significantly the cytotoxicity of doxorubicin in skin fibroblasts and cardiomyocytes after 24 h of incubation. The best cytoprotective effect of ozone was reached to 30 µg/mL with a plateau phase at higher concentration. Ozone also demonstrated anti-inflammatory effects decreasing significantly the interleukins and proinflammatory mediators in both cells. CONCLUSION: Ozone exerts cardioprotective and dermatoprotective effects during incubation with doxorubicin, and the involved mechanisms are mediated by its anti-inflammatory effects. The overall picture described herein is a pilot study for preclinical studies in oncology.

Correlation between gamma glutamyltransferase fractions and bone quality.

Gamma-glutamyltransferase (GGT) has been recently identified as a bone-resorbing factor. The aim of this study was to investigate the association between plasma GGT fractions levels and bone quality. Plasma GGT fractions were analysed by gel-filtration chromatography. Bone quality was established quantitatively by two micro-CT derived microarchitectural parameters: the BV/TV (mineralised bone volume/total volume), and the SMI (structure model index) that describes the rod-like (low resistant) or plate-like (high-resistant) shape of bone trabeculae. We enrolled 93 patients hospitalised for elective total hip replacement (group Arthrosis, n=46) or for proximal femoral fracture (group Fracture, n=47). Patients within the first quartile of BV/TV (Q1, osteoporotic patients, n=6) showed higher levels of b-GGT fraction [median (min-max): 3.37 (1.42­6.81)] compared to patients with normal bone density (fourth quartile Q4, n=10; 1.40 (0.83­4.36); p=0.0393]. Also, according to SMI, b-GGT value was higher in the subgroup with bone fragility [Q1, n=8: 1.36 (0.43­4.36); Q4, n=8: 5.10 (1.4 ­7.60); p=0.0117]. In conclusion, patients characterised by fragile bone structure showed specifically higher levels of plasma b-GGT activity thus suggesting fractional GGT analysis as a possible biomarker in the diagnosis of osteoporosis.

Ozone autohemotherapy induces long-term cerebral metabolic changes in multiple sclerosis patients.

Ozone autohemotherapy is an emerging therapeutic technique that is gaining increasing importance in treating neurological disorders. A validated and standard methodology to assess the effect of such therapy on brain metabolism and circulation is however still lacking. We used a near-infrared spectroscopy (NIRS) system to monitor the cerebral metabolism and a transcranial Doppler (TCD) to monitor the blood flow velocity in the middle cerebral arteries. Fifty-four subjects (32 neurological patients and 22 controls) were tested before, during, and after ozone autohemotherapy. We monitored the concentration changes in the level of oxygenated and deoxygenated haemoglobin, and in the level of the Cytochrome-c-oxidase (CYT-c). As a primary endpoint of the work, we showed the changes in the brain metabolism and circulation of the entire population. The concentration of oxygenated haemoglobin increased after the reinjection of the ozoned blood and remained higher than the beginning for another 1.5 hours. The concentration of the deoxygenated haemoglobin decreased during the therapy and the CYT-c concentration markedly increased about 1 hour after the reinjection. No significant changes were observed on the blood flow velocity. As secondary endpoint, we compared the NIRS metabolic pattern of 20 remitting-relapsing multiple sclerosis (MS) patients against 20 controls. We showed that by using only 7 NIRS variables it was possible to characterize the metabolic brain pattern of the two groups of subjects. The MS subjects showed a marked increase of the CYT-c activity and concentration about 40 minutes after the end of the autohemotherapy, possibly revealing a reduction of the chronic oxidative stress level typical of MS sufferers. From a technical point of view, this preliminary study showed that NIRS could be useful to show the effects of ozone autohemotherapy at cerebral level, in a long-term monitoring. The clinical result of this study is the quantitative measurement of the CYT-c level changes in MS induced by ozone autohemotherapy.

Time and time-frequency analysis of near-infrared signals for the assessment of ozone autohemotherapy long-term effects in multiple sclerosis.

Ozone autohemotherapy is an emerging therapeutic technique that is gaining increasing importance in treating neurological disorders. A validated and standard methodology to assess the effect of such therapy on brain metabolism and circulation is however still lacking. We used a near-infrared spectroscopy system (NIRS) to monitor the cerebral oxygenation of 9 subjects: 4 remitting-relapsing multiple sclerosis (MS) sufferers and 5 controls. Subjects were tested before, during, and after ozone autohemotherapy. We monitored the concentration changes in the level of oxygenated and deoxygenated haemoglobin, and in the level of the Cytochrome-c-oxidase (CYT-c). From the time and time-frequency analysis of the NIRS signals we extracted 128 variables, which were used to characterize the metabolic brain pattern during the therapy. We showed that by using only 7 NIRS variables out of 128 it is possible to characterize the metabolic brain pattern of the two groups of subjects. The MS subjects showed a marked increase of the CYT-c activity and concentration about 40 minutes after the end of the autohemotherapy, possibly revealing a reduction of the chronic oxidative stress level typical of MS sufferers. From a technical point of view, this preliminary study showed that NIRS could be useful to show the effects of ozone autohemotherapy at cerebral level, in a long term monitoring. The clinical result of this study is the quantitative measurement of the CYT-c level changes in MS induced by ozone autohemotherapy.

[Preliminary study to evaluate the meaning of GGT fractions analysis in a population of workers previously exposed to asbestos]. / Studio preliminare volto all'inquadramento del significato preventive del dosaggio di frazioni di GGT in una popolazione di lavoratori ex-esposti ad Amianto.

The GGT enzyme, considered for years only as a marker of liver disease and alcohol abuse, has now revealed a risk of death for many causes. Through a molecular exclusion chromatography on FPLC system (Fast Protein Liquid Chromatography), it is possible to discriminate four fractions of GGT, defined according to the molecular weight: big-GGT, medium-GGT, small-GGT and free-GGT. The objective was to study the preventing meaning of GGT fractions for asbestos-related diseases. This study was conducted on 129 workers previously exposed to asbestos, 22 patients affected by Malignant Pleural Mesothelioma and 107 healthy workers. Our data demonstrated a statistical significant correlation between the fraction free-GGT with the presence of MPM, suggesting a possible role for this molecule as a biomarker for MPM diagnosis. However, being a preliminary study, further studies are warranted to confirm our results.

Transanal haemorrhoidal dearterialisation: nonexcisional surgery for the treatment of haemorrhoidal disease.

BACKGROUND: Transanal haemorrhoidal dearterialisation (THD) is a nonexcisional surgical technique for the treatment of piles, consisting in the ligation of the distal branches of the superior rectal artery, resulting in a reduction of blood flow and decongestion of the haemorrhoidal plexus. The aim of this study was to assess the long-term efficacy of this treatment. METHODS: The procedure was carried out using a proctoscope with a Doppler probe. The terminal branches were located with Doppler and then sutured. RESULTS: From January 2000 to May 2006, we performed THD in 330 patients (180 men; mean age, 52.4 years), including 138 second-degree, 162 third-degree and 30 fourth-degree haemorrhoids. There were 23 postoperative complications (7 cases of bleeding, 5 thrombosed piles, 4 rectal haematomas, 2 anal fissures, 2 cases of dysuria, 1 of haematuria and 2 needle ruptures). The mean postoperative pain score was 1.32 on a visual analog scale. 219 patients were followed for a mean of 46 months (range, 22-79), including 100 patients with second-degree, 104 with third-degree and 15 with fourth-degree haemorrhoids. The operation completely resolved the symptoms in 132 patients (92.5%) with preoperative bleeding and in 110 patients (92%) with preoperative prolapse. CONCLUSIONS: The efficacy and relapse rate of this procedure appears to be similar to that of traditional surgery and stapled haemorrhoidopexy. The technique was effective and safe for all degrees of haemorrhoids because of the excellent results, low complication rate and minor postoperative pain.

Antioxidant capacity and protein oxidation in cerebrospinal fluid of amyotrophic lateral sclerosis.

BACKGROUND: The causes of Amyotrophic Lateral Sclerosis (ALS) are unknown. A bulk of evidence supports the hypothesis that oxidative stress and mitochondrial dysfunction can be implicated in ALS pathogenesis. METHODS =: We assessed, in cerebrospinal fluid (CSF) and in plasma of 49 ALS patients and 8 controls, the amount of oxidized proteins (AOPP, advanced oxidation protein products), the total antioxidant capacity (FRA, the ferric reducing ability), and, in CSF, two oxidation products, the 4-hydroxynonenal and the sum of nitrites plus nitrates. RESULTS: The FRA was decreased (p = 0.003) in CSF, and AOPP were increased in both CSF (p = 0.0039) and plasma (p = 0.001) of ALS patients. The content of AOPP was differently represented in CSF of ALS clinical subsets, resulting in increase in the common and pseudopolyneuropathic forms (p < 0.001) and nearly undetectable in the bulbar form, as in controls. The sum of nitrites plus nitrates and 4-hydroxynonenal were unchanged in ALS patients compared with controls. CONCLUSION: Our results, while confirming the occurrence of oxidative stress in ALS, indicate how its effects can be stratified and therefore implicated differently in the pathogenesis of different clinical forms of ALS.

On the incorporation of the non-steroidal anti-inflammatory naproxen into cationic O/W microemulsions.

Microemulsions (ME) containing hexadecyltrimethylammonium bromide (HTAB)/ethanol as surfactant, isopropylmyristate (IM) or butylstearate (BS) as oil phase and aqueous buffer were studied. Pseudo-ternary phase diagrams of the investigated systems were obtained at constant surfactant/cosurfactant molar ratio (1:5) by titration in order to characterize the proportions between the components to obtain clear systems. Oil in water microemulsions were prepared in a wide range of phase volume (phi). UV-vis absorption spectra of naproxen at pH 5.5 showed that the solubility of Np increases significantly in the presence of O/W ME in high phase volumes. For both, IM and BS microemulsions, the dynamic light scattering experiments showed that the size of the oil droplets remains constant in low values of phi, increasing abruptly in high phi values. Phase solubility study revealed that for both IM and BS microemulsions, the drug incorporation followed a straight-line profile in all range of phi. The data could be analyzed through the phase-separation model and the association constants (K) calculated varied from 27 to 90 M(-1), depending on the pH and on the microemulsion oil phase.

[Gastroesophageal reflux and laryngopharyngeal disorders: pH-metric essay of the acid exposure of the proximal and distal esophagus]. / Reflusso gastro-esofageo e disturbi faringo-laringei: valutazione pH-metrica dell'esposizione acida esofagea prossimale e distale.

AIM: The purpose of this study is to verify the role of gastroesophageal reflux as responsible for otolaryngological symptoms; it is often difficult to identify, both because of its subtle and aspecific clinical-endoscopic picture and because the traditional distal esophageal pHmetry may show readings which are still within the norm at this level. The esophageal pHmetry carried out at proximal level gives greater diagnostic accuracy. METHODS: We use a catheter with 3 antimony electrodes, 2 of them placed at the esophageal level, respectively at 5 and 20 cm above the inferior esophageal sphincter, and 1 in the stomach. We studied 3 groups of patients: 41 asymptomatic no-refluxer patients (group I, control), 59 refluxer patients with only typical esophageal symptoms (group II) and 68 patients with laryngo-pharyngeal symptoms suffering from acid reflux (group III). RESULTS: At both the proximal and distal esophageal levels, the reflux, with reference to control, turned out to be significantly higher in groups II and III, both as regards the number of episodes (p<0.01), the time of acid exposition (p<0.01), the length of the longer reflux (p<0.01), whereas no differences were found between groups II and III. The proximal esophageal acid refluxes in both groups II and III occurred mainly in the upright position: alone (57.2% and 62.5% respectively) or combined with supine position (23.8% and 34.0% respectively). CONCLUSION: Our experience suggests that the esophago-gastric pHmetry with 3 electrodes represents an effective procedure for the correlation between otolaryngological symptoms and gastro-esophageal reflux.

gamma-Glutamyl transpeptidase catalyses the extracellular detoxification of cisplatin in a human cell line derived from the proximal convoluted tubule of the kidney.

Nephrotoxicity is a side-effect and the main factor limiting the clinical use of cisplatin. In vivo, the administration of the cysteine-containing tripeptide glutathione (GSH) has been found to reduce nephrotoxicity, but the biochemical mechanism of this protective action is not fully understood. The present study was designed to gain insights into the mechanism by which GSH prevents cisplatin nephrotoxicity. We also wanted to verify the hypothesis of whether the protective action of GSH is mediated by products of the extracellular breakdown of GSH catalysed by gamma-glutamyl transpeptidase (GGT), an enzyme that is highly expressed in kidney tubular cells. The study was performed in HK-2 cells, derived from the immortalisation of human kidney proximal tubule cells. We investigated the influence of modulators of GGT activity and/or thiols on the antiproliferative activity of cisplatin and on the intracellular GSH content. We determined the antiproliferative activity of cisplatin, platinum cellular accumulation and DNA platination following precomplexing of the drug with thiols. The antiproliferative effect of cisplatin was minimally affected by the addition of GSH. However, when the antiproliferative assay was performed in the presence of glycyl-glycine (GlyGly), to serve as a transpeptidation acceptor and thus to stimulate GGT-mediated GSH catabolism, cisplatin-induced growth inhibition was largely prevented. This effect was not mediated through an increase of intracellular GSH levels, which were not affected by the GlyGly supplementation. The thiol dipeptide cysteinyl-glycine, i.e. the GSH catabolite generated by GGT activity, showed a higher reactivity against cisplatin in vitro than GSH, as was shown by the more rapid oxidation of its -SH groups. The cisplatin/GSH or cisplatin/cysteinyl-glycine adducts did not display an antiproliferative effect. However, 2 h precomplexing with GSH in the presence of GGT, or directly with the GSH catabolite cysteinyl-glycine, decreased the antiproliferative effect of cisplatin and drug-induced DNA platination to a greater extent than precomplexing with GSH alone. The results of the present study show that, in HK-2 cells, extracellular GSH decreases the antiproliferative effects of cisplatin only upon its hydrolysis by GGT, thereby supporting the hypothesis that the extracellular metabolism of GSH by GGT plays a role in modulating cisplatin nephrotoxicity. A primary role in the protection of HK-2 cells appears to be played by cysteinyl-glycine, the proximal product of the GGT-mediated hydrolysis of GSH, which shows a high reactivity against CDDP resulting in the rapid inactivation of the drug.

Sentinel node biopsy and internal mammary lymphatic mapping in breast cancer.

BACKGROUND: Currently outer quadrant breast tumors are not felt to have significant drainage to the internal mammary nodal chain. We evaluated the incidence of internal mammary sentinel nodes (IMSN) found with lymphoscintigraphy for all breast quadrants. METHODS: Eighty women were prospectively studied by technitium-sulfur colloid injection, nuclear medicine imaging, and intraoperative gamma probe identification of sentinel nodes. IMSN detected were surgically removed. RESULTS: Ten of 80 ( 12%) patients had IMSN identified in addition to axillary sentinel nodes (AXSN). Four tumors were located medially, 6 (60%) were in the outer quadrants. Metastatic disease was present in 3 of 10 women. Patients with positive IMSN also had positive AXSN. CONCLUSIONS: Patients undergoing lymphatic mapping for the management of breast cancer should have radiolabelled tracer and gamma probe sentinel node identification regardless of tumor location in the breast.

[Sclerosing peritonitis. A complication of LeVeen peritoneovenous shunt]. / Peritonite incapsulante. Una complicanza dello shunt peritoneo-venoso di LeVeen.

Sclerosing peritonitis (abdominal cocoon syndrome) is a rare chronic affection of the peritoneum; its etiology is multifactorial and it affects all ages. Capsulating membranes seem to grow from a poorly cellular connective deposition in many layers on the intestinal peritoneum and are casually detected by surgery or autopsy. The placement of the peritoneovenous shunt can favour the deposition of fibrin on the visceral peritoneum, determining the formation of sclerosing membranes. When mechanical occlusion occurs, surgery is the choice therapy in order to remove the obstacle and, if possible, the membranes as well.