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Long COVID-19-related changes in physiology includes alterations in performing muscle work as fatigue. Data available do not allow us to define the usefulness of physical activity to attenuate long COVID-19 functional modifications. The present observational study investigates the effects of physical activity on the perception of fatigue, maximum power output, sleep, and cognitive modifications in subjects affected by long COVID-19, distinguishing between active and sedentary subjects. The data demonstrated the following: the perception of fatigue 1 year after the end of virus positivity was significantly reduced with respect to that observed after 6 months by more than 50% more in active subjects compared to sedentary ones; 6 months after the end of virus positivity, the force developed by active subjects was reduced (RM factor: p < 0.001, η2p = 0.527, post hoc: p < 0.001), but the reduction was more pronounced in sedentary ones (mean difference = 38.499 W); poor sleep quality and mild cognitive impairment were assessed in both active and sedentary subjects. In conclusion, the study suggests that the long COVID-19 fatigue was lower in active subjects respect to sedentary ones. A comparative analysis performed due to the overlap of functional alterations between long COVID-19 and ME/CFS showed that in a small percentage of the enrolled subjects (8%), the symptomatology reflected that of ME/CFS and was independent of the individual physical capacities.

In order to maintain a state of well-being, the cell needs a functional control center that allows it to respond to changes in the internal and surrounding environments and, at the same time, carry out the necessary metabolic functions. In this review, we identify the mitochondrion as such an "agora", in which three main messengers are able to collaborate and activate adaptive response mechanisms. Such response generators, which we have identified as H 2 O 2 , Ca 2+ , and Zn 2+ , are capable of "reading" the environment and talking to each other in cooperation with the mitochondrion. In this manner, these messengers exchange information and generate a holistic response of the whole cell, dependent on its functional state. In this review, to corroborate this claim, we analyzed the role these actors, which in the review we call "sensors", play in the regulation of skeletal muscle contractile capacities chosen as a model of crosstalk between Ca 2+ , Zn 2+ , and H 2 O 2 .

In the last decade, clear evidence has emerged that the cellular components of skeletal muscle are important sites for the release of proteins and peptides called "myokines", suggesting that skeletal muscle plays the role of a secretory organ. After their secretion by muscles, these factors serve many biological functions, including the exertion of complex autocrine, paracrine and/or endocrine effects. In sum, myokines affect complex multi-organ processes, such as skeletal muscle trophism, metabolism, angiogenesis and immunological response to different physiological (physical activity, aging, etc.) or pathological states (cachexia, dysmetabolic conditions, chronic inflammation, etc.). The aim of this review is to describe in detail a number of myokines that are, to varying degrees, involved in skeletal muscle aging processes and belong to the group of proteins present in the functional environment surrounding the muscle cell known as the "Niche". The particular myokines described are those that, acting both from within the cell and in an autocrine manner, have a defined relationship with the modulation of oxidative stress in muscle cells (mature or stem) involved in the regulatory (metabolic or regenerative) processes of muscle aging. Myostatin, IGF-1, NGF, S100 and irisin are examples of specific myokines that have peculiar features in their mechanisms of action. In particular, the potential role of one of the most recently characterized myokines-irisin, directly linked to an active lifestyle-in reducing if not reversing senescence-induced oxidative damage is discussed in terms of its possible application as an agent able to counteract the deleterious effects of muscle aging.

Prostate cancer is the second most common malignancy of men in the western countries. Fatigue is the most stressful symptom of which patients with metastatic castration-resistant prostate cancer (mCRPC) complain. The aim of this article was to report available data about the incidence of fatigue in mCRPC and its correlates. The design involved a systematic review to define incidence of fatigue according to Common Toxicity Criteria in randomized controlled trials of medical treatments of mCRPC and according to International Classification of Diseases Revision 10 (ICD-10) criteria, and to define prevalence and correlates of fatigue in patients with mCRPC. The data source used was PubMed. In December 2014, 2 PubMed searches were performed and the clinical data on the occurrence of cancer-related fatigue along the course of metastatic disease, and findings about its pathogenesis were summarized. Cancer-related fatigue, as defined according to ICD-10 criteria, was reported in 12% to 21% of patients, and prospective clinical trials showed a prevalence of Grade 3/4 fatigue according to Common Toxicity Criteria of 0% to 18%. A list of possible correlates of fatigue in mCRPC, either patient-related, disease-related, or treatment-related, is proposed herein for future studies. Antineoplastic treatments, particularly chemotherapy and radiotherapy, have a major role in the pathogenesis of fatigue in metastatic prostate cancer, however, hormonal treatments remain the most prevalent therapies. A standardized tool for multidimensional assessment of fatigue in metastatic cancer is suggested., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The results of cytotoxic therapy in the second-line setting of metastatic castration-resistant prostate cancer have demonstrated that disease is poorly controlled after taxane resistance with a time to progression of 3 months or less. Many trials of second-line chemotherapy have been disappointing. However, most of patients with docetaxel-pretreated castration-resistant disease receive a second-line chemotherapy. Molecular mechanism of castration resistance and docetaxel resistance is resumed, and clinical trials of second-line chemotherapy after docetaxel progression are reviewed. Reintroduction of docetaxel after a drug-free interval is an active treatment in docetaxel-pretreated patients, and only recently a prospective study documented a survival benefit of 2.4 months after second-line taxane-based chemotherapy of metastatic docetaxel-resistant prostate cancer. Although a second-line chemotherapy with a taxane could improve overall survival, a change of biology of castration-resistant prostate cancer after docetaxel is suggested, as inferred by the renewed hormonal sensitivity, whose role on survival remains unknown, and from the activity of antiangiogenic drugs.

Background: In the clinical setting of metastatic castration-resistant prostate cancer the aim of treatment is palliation. Palliation can refer to symptom management or non-curative treatments. Patient-reported outcome is any outcome based on data provided by patients. The aim of this paper is to perform a systematic review of clinical trials including a patient-reported outcome assessment in patients treated with cytotoxic chemotherapy, and to compare their results by traditional medical and patient-reported outcomes assessment., Methods: In November 2009 a literature search for published studies was undertaken. Selected phase-3 studies were primarily evaluated on the quality of patient-reported outcomes reporting and assessment methodology., Findings: Health-related quality of life assessment was the most common endpoint, pain control the second one. Results of patient-reported and traditional endpoints analysis are resumed, as well as methodology assessment and quality of patient-reported outcomes reporting. Frequently, methodologic limitations affect patient-reported outcomes assessment in clinical trials, either data analysis, particularly not reporting individual scores of health-related quality of life questionnaires, statistical corrections, limited efforts to avoid missing data, or lacking report of duration of palliative response., Conclusions: Results of trials can differ if different outcomes, medical or patient-reported, are considered in the analysis. Cytotoxic chemotherapy of metastatic castration-resistant prostate cancer is a challenging issue. A survival benefit is reported only for docetaxel, but this treatment is not always feasible. In all patients, initiation of chemotherapy should be based on patient's preferences within discussion of individual risk and benefit, particularly in patients with extensive asymptomatic and symptomatic metastases., (2010 Elsevier Ltd. All rights reserved.)

A poor prognosis for patients with Stage IIIA clinical N2 treated by surgery alone has led clinical researchers to find a new treatment modality to improve the curative potential of surgery. Many Phas II trials have been carried out with induction chemo- or chemo-radiotherapy prior to surgery. From June 1988 to July 1991, 46 patients with non-small cell lung cancer (NSCLC) Stage IIIA clinical N2 entered a Phase II induction-chemotherapy trial. Patients received 2-3 cycles of high-dose cisplatin and etoposide. Forty-five were evaluable for response; the response rate was 82% (37/45: 3 CR, 34 PR). Toxicity was primarily hematologic. Surgical resection was performed in 35 patients; radical resection was possible in 28 patients (62%); three patients were incompletely resected and two patients were only explored. Three deaths were surgery-related. Median survival was 24.5 months with a 2-year survival of 53%. Cisplatin with etoposide is an active and safe induction chemotherapy regimen for NSCLC Stage IIIA N2 with a high response rate. The median survival seems to be prolonged and therefore, randomized trials are needed to compare this approach with other treatment modalities.

In an attempt to improve the curative potential of surgery, 46 patients with unresectable Stage IIIA (Clinical N2) non-small cell lung cancer received neoadjuvant chemotherapy with cisplatin and etoposide. After 2 or 3 cycles, 45 patients were evaluable for response; the overall response rate was 82% (37/45) with 3 complete and 34 partial responses. Toxicity was primarily hematologic. Surgical exploration was performed on 35 patients, but resection was possible in only 33 (73%). Of these, 28 resections were complete (62%). Four patients (2CR, 2PR; 9%) had no tumor in biopsy specimen. Three deaths were surgery-related. Median survival of the entire 46 patients was 24.5 months with a 2-year survival of 53%. Cisplatin and etoposide is an effective chemotherapeutic regimen for regionally advanced non-small cell lung cancer; the resection and survival rates justify further trials to compare this approach to other treatment modalities.

Fifty-six breast cancer patients with metastatic spinal cord compression were consecutively treated with radiation therapy alone. All patients received steroids plus chemotherapy and/or hormonal therapy. Emergency radiation therapy was administered using a split-course regimen: 5 Gy for 3 days, stopped for 4 days and, only in responders, a further 3 Gy for 5 days (time dose fractionation 68). Median follow-up was 22 months (range, 4 to 52 months). Response and survival were assessed on the basis of, pretreatment and posttreatment walking capacity, presence of vertebral body collapse or osteolysis, presence of other metastatic sites apart from bone and chemotherapy and/or hormonal therapy. In 89% of patients with back pain the pain disappeared or lessened. Four of 6 cases (67%) with urinary dysfunction responded to radiation therapy. Of 35 cases with motor dysfunction at the time of diagnosis, 21 (60%) regained the ability to walk and another five (14%) who were able to walk with support at diagnosis did not deteriorate. All 21 cases without motor deficits before treatment maintained good motor performance after radiation therapy. Response to therapy was better in pretreatment walking than in nonwalking patients (97% vs 69%; p less than 0.02). Probability of duration of response at 1 year was 59% and 10% for posttreatment walking and nonwalking patients, respectively (p less than 0.0001). One year survival probability was 66% for posttreatment walking and 10% for posttreatment nonwalking patients, respectively (p less than 0.0001). Pretreatment and posttreatment ambulatory status were the most important prognostic factors.

Interstitial pneumonia is one of the major causes of morbidity and mortality after bone-marrow transplantation. We here report a series of 58 patients suffering from hematological malignancies who received HLA-matched T-lymphocyte depleted bone-marrow transplants between July 1985 and January 1990. Interstitial pneumonia occurred in 7/58 patients (12%) and was fatal in six. Three different pre-bone-marrow transplantation conditioning regimens were employed. Total body irradiation was delivered according to a hyperfractionated scheme of 12 fractions given three per day 5 hr apart for 4 days. Twenty-three patients received 36 mg/Kg procarbazine, 1275 UL/Kg antithymocite globulin, 14.4 Gy hyperfractionated total body irradiation and 120 mg/Kg cyclophosphamide. Only one patient developed interstitial pneumonia, but two rejected the graft and 10 relapsed. As a consequence, the total hyperfractionated scheme was increased to 15,6 Gy, cyclophosphamide to 200 mg/Kg, antithymocite globulin to 3400 UL/Kg and procarbazine eliminated. There were three cases of interstitial pneumonia, no rejection and four relapses in the 17 patients who received this regimen. In the last 18 patients hyperfractionated total body irradiation was reduced to 15 Gy, cyclophosphamide to 100 mg/Kg, and 10 mg/Kg of the myeloablative agent thiothepa added to enhance the cytoreductive effect without significantly increasing extramedullary toxicity. Three cases of interstitial pneumonia, one relapse but no rejection were recorded. Our results demonstrate that the absence of graft-versus-host disease due to T-cell depletion, and radio-chemotherapy doses and schedules used for the conditioning regimen each contributed to reducing the risk of interstitial pneumonitis. Hyperfractionated total body irradiation therefore, seems to play an important role in lowering the incidence of this complication.

From July 1985 to December 1989, 72 evaluable patients aged between 6 and 51 (median age 27 years) suffering from haematological malignancies received an allogeneic bone marrow transplant (BMT) depleted of T-lymphocytes to reduce the risk of graft-versus-host-disease (GvHD); 57 were matched and 15 mismatched. Three different conditioning regimens were used in an effort to enhance cytoreduction without increase extramedullary toxicity. Mismatched patients were treated with more immunosuppressive regimens. Total body irradiation (TBI) was given in three doses per day, 5 h apart, over 4 days for a total of 12 fractions. The dose to the lungs was 14.4, 15.6 and 9 Gy according to the conditioning regimen. The incidence of interstitial pneumonia (IP) was 12.3% in matched and 46.7% in mismatched patients. Our results seem to indicate that lung toxicity is correlated with the intensity of the conditioning regimen, the stage of disease and, in mismatched patients, with the degree of human leucocyte antigen (HLA) disparity and the poor post-BMT reconstitution, rather than the radiotherapy dose delivered to the lungs. On the contrary, the hyperfractionated scheme adopted, the absence of GvHD and, perhaps, the post-TBI administration of cyclophosphamide all seem to have contributed to the low incidence of IP in our matched patients.

The Authors report their personal experience of surgical treatment following neo-adjuvant therapy in NSCLC (III a N2) in order to assess: 1) the feasibility and safety of surgical treatment following major responses to neoadjuvant chemotherapy; 2) the sectile rate; and 3) the survival rate. Preliminary results show that: 1) chemotherapy using cisplatin and VP-16 gives a high rate of major responses in these patients; 2) surgery is feasible; 3) there is high radical sectile rate; 4) further research is needed to obtain statistical significance.

We report our experience in the treatment of nasopharyngeal carcinoma with intracavitary curietherapy to cure small recurring carcinomas or residual local disease 2-6 weeks after completing external radiotherapy. Since 1984, 10 patients have received intracavitary radiotherapy with customized molds charged with Ir 192. Six of them received a boost dose because of residual disease and for local recurrence. The technique we employed to shape the molds is described, together with the mode of use and the doses to target volume. Due to both the small number of treated cases and the short follow-up, no significant conclusions could be drawn relative to survival time. However, it must be stressed that this therapeutic approach gives a high local control rate with no severe side-effects or sequelae.

This was a non-randomized prospective study on the "sandwich" radiosurgical treatment of resectable rectal and rectosigmoid carcinomas. From December 1984 to December 1989, 100 patients were treated 86 of them are now evaluable. Mean follow-up was 38 months (range: 9-69). Surgery was abdomino-perineal resection in 33 cases and anterior resection in 53 cases. Radiotherapy was preoperative pelvic irradiation, with a single 500-Gy fraction, the day before surgery. To stages B2, C1 and C2 patients (Astler and Coller) postoperative radiotherapy was administered for a total dose of 4500 Gy (180 Gy/fraction, 5 fractions/week), with box technique, from a Co 60 unit or Linear Accelerator (photon 18 MV). Preliminary results indicate 8% (7/86) local recurrences and 9.3% (8/86) distant metastases. Five-year actuarial disease-free survival is 63.2% +/- 8 for stage B1, 55.6% +/- 19 for stage B2, and 40.2% +/- 13 for stages C1 + C2. Overall 5-year actuarial disease-free survival is 53% +/- 10. No lethal or severe complications were observed following treatment.

Between January 1983 and December 1987, 77 patients with cervical and endometrial carcinoma (40 and 37 cases, respectively) were studied with a diagnostic protocol which included lymphangiography and abdomino-pelvic CT. The only administered treatment was radiation since all patients were considered inoperable or had non-resectable disease. Median age was 55 years (range 29-77). Median follow-up was 44 months-minimum 24, maximum 72 months. Subdiaphragmatic nodes were considered as pathologic even when just one of the two techniques demonstrated their involvement. Radiotherapy doses and volumes varied according to these findings (45 Gy to pelvis as a precautional dose; 6-8 Gy booster dose in N1 cases; 45 Gy to the periaortic area in N4 cases). The two diagnostic techniques agreed as to the presence/absence of pathologic nodes in 50 (64.9%) and 12 (15.6%) patients, respectively. There was disagreement between CT and lymphangiographic findings in 12 patients (15.6%) as regards the pelvic area and in 8 patients as regards the periaortic area (10.4%; 5 of the 8 also figured in the pelvic group). Actuarial 5-year disease-free survival for both groups, summing up stages I, II and III, goes as follows: cervical carcinoma patients: 47% (N0 cases 56%, N1-N4 33%, p = 0.07) and endometrial carcinoma group: 74.5% (no difference was found between N0 and N1 cases). Higher diagnostic accuracy seems to be obtained when CT is combined with lymphangiography than when either of them is performed alone. Therefore, the combined use of the two techniques could have a precise diagnostic role.

A non-randomized prospective trial in which radiotherapy (RT) alone played the major role in the treatment of metastatic spinal cord compression (MSCC) is reported. Diagnosis was formulated on myelography and/or myelography plus computed thomography (CT). Of 51 cases treated, 48 are evaluable. The therapy consisted of radiation alone (42 cases) or decompressive laminectomy followed by radiotherapy (6 cases). Surgery was performed when the site of the primary tumor was unknown. The group of patients who received radiotherapy alone (42 of 48 evaluable cases) are analysed in this report. Medium to high doses of steroids were administered to all patients depending on the gravity of the case. Patients with chemo- or hormone-responsive primary tumors also received chemotherapy and/or hormone therapy. Pain relief, assessed by comparing use of narcotics and minor analgesics before and after treatment, was achieved in 54% cases (confidence limits, CL = 38-69%). In 36% (CL = 22-51%) of patients back pain diminished to the point when only milder analgesics were necessary (partial remission). Motor performance, based on patients' ability to walk, improved in 48% cases (CL = 31-65%). The 19 patients who were ambulatory before RT, did not deteriorate after treatment. Sphincter function, evaluated by patient's need for indwelling catheter, improved in 3 of 7 automatic dysfunction cases. It was found that early diagnosis was more important than primary tumor type for predicting a good was found that early diagnosis was more important than primary tumor type for predicting a good prognosis. In fact, all ambulating patients responded to treatment independent of the radiosensitivity of the tumor histology.(ABSTRACT TRUNCATED AT 250 WORDS)

Twenty patients suffering from malignant hemopathies (mean age 31.7 years) were given hyperfractionated total body irradiation (TBI) (120 cGy/3 fractions per day: total dose = 1440 cGy/4 days) as conditioning for T-depleted HLA identical allogeneic bone marrow transplantation. At an average of 12 months (range of 4.5-22 months) follow-up there were two cases of early death and two cases (11%) of rejection. There were no cases of acute or chronic graft versus host disease (GVHD) nor cases of interstitial pneumonitis. The average time for durable engraftment was 22 days. Disease-free survival at 12 months was 65%. To improve the results and further reduce the percent of rejection, the authors propose intensifying the immunosuppressive conditioning by increasing the cyclophosphamide dose and that of TBI so that a total dose of 1560 cGy is reached.

The authors report their technique for breast radiotherapy following conservative surgery (quadrantectomy + axillary dissection). The breast and chest wall are irradiated with photons from a 60Co unit through two fixed opposing tangential fields. The posterior field edges must be parallel and coplanar to the chest wall. A routine treatment plan using simulator, pantograph and computerized console is standardized by mathematical formulae elaborated from geometric breast measurement parameters. Gammagraphies acquired prior to and during therapy allow verification and control of treatment parameters. For 35 patients the therapy plan as described was compared with that obtained by CT images. Our procedure proved valid and an accurate treatment plan could be elaborated even without CT images. The use of wedges, half-field blocks and the dose scattered to the contralateral breast are also discussed.

Metastatic Spinal Cord Compression (MSCC), an oncologic emergency, is a frequent complication of many neoplastic diseases in an advanced stage. Our experience is reported, which was obtained with a series of 61 patients following a diagnostic-therapeutic protocol aimed at early diagnosing MSCC and at assigning the major role in therapy to radiotherapy (RT) alone. Fifty-seven patients with an average follow-up of 13 months (range 4-26) were evaluable. Diagnosis was always made by means of myelography and/or myelography plus CT. In 50 cases the treatment consisted in RT alone and the remaining 7 patients had surgery before RT because of diagnostic doubts; in 1 case the patient was operated on because stabilization was necessary. A dose of 30 Gy was delivered, over 2 weeks, (TDF = 62) to those tumors which were considered as radiation-responsive and having a better prognosis (myeloma, lymphoma), whereas all the other histologies were given a split-course regimen (5 Gy x 3 days, stop x 4 days, +/- 3 Gy x 5 days; TDF = 68). All patients received medium or high doses of steroid depending on the degree of neurologic involvement. Patients with chemo/hormone-responsive primary tumors also received chemotherapy and/or hormone therapy. The clinical parameters considered in evaluating the response to treatment were backache, motor performance, and sphincter function. Respectively 86%, 47% and 44% of patients responded. Early diagnosis was the most important prognostic factor, whereas histology of the primary tumor was important in cases with severe neurologic damage only. The results obtained are similar to those reported in literature and confirm the value of the diagnostic-therapeutic approach used, which suggests continuing this trial.

From June 1977 through June 1987, 46 patients (36 evaluable) affected by stage I and II non-bulky testicular seminoma were treated with postoperative telecobaltotherapy (TCT). In stage I seminomas, radiotherapy was extended to the omolateral iliac and the para-aortic areas (total dose: 30 Gy over 4 weeks). In stage II seminomas, the subdiaphragmatic lymph nodes were irradiated with 40-45 Gy over 5-6 weeks; after an interval of one month the subdiaphragmatic lymph nodes were irradiated again with a total dose of 25 Gy over 3.5 weeks. Minimal follow-up lasted two years and maximum ten years (average: 5.5). Two (5.5%) recurrences occurred, but salvage radiotherapy and salvage chemotherapy respectively allowed a complete permanent remission. One patient died from a different neoplasia with no evidence of testicular involvement. The 5-year actuarial survival is 96.6 +/- 3.4. In 20% of the patients the side effects were nausea and/or vomiting, easily controlled. No late complications were observed.