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Patients with glaucoma can show blood flow anomalies at the eye vessel level. A causal relationship is reasonably expected, but so far, it has not been demonstrated. Traditional Chinese medicine indicates that acupuncture can promote specific blood perfusion in specific body districts. Ninety-eight patients with open-angle glaucoma were treated with an ultralow light–level laser, according to a specific acupuncture protocol, and their blood flow was measured before and after a six-week treatment cycle. Doppler measurements showed significant modifications in both pulsatility and resistivity indexes. The most relevant outcome of this study is that the applied treatment demonstrated its effectiveness not only in vasodilation but also in perfusion control that seems to restore appropriate functionality. The protocol therefore should be investigated in future controlled studies and perhaps in other blood perfusion–related pathologies. [ABSTRACT FROM AUTHOR]

Abstract: The risk of falling is rather high among elderly people. Indexes obtained through the Romberg stabilometric test on a force platform have been suggested to be correlated with the risk of falling. This work aimed to test the effectiveness of auriculopuncture and ultralow-power laserpuncture versus placebo (sham stimulation) in improving postural control in an elderly population. Balance performance was measured on a force platform before and after both forms of stimulation. Main balance parameters pointed to an average short-term improvement of about 15% 1 hour after treatment and 5-10% after an interval of 3 days. However, a few participants showed a better than 30% improvement with the same parameters. Although the sample size does not allow reliable statistical analysis, the modifications are remarkable and some differences are observed between the two kinds of stimulation. Further testing with larger sized groups and including one further group using both stimulations is suggested. Although postural instability has to be defined as multi-factorial, it is often associated with balance dysfunctions that cannot be related to vestibular or central impairments but rather to proprioceptive deficits. A significant role may be ascribed to (even subliminal) nociceptive interferences with proprioceptive inputs and to a reduced capacity for updating cortical motor control models in the case of progressively declining locomotor capabilities. The explanation tentatively put forward to account for the results observed in the present preliminary study is that laser acupuncture and auriculopuncture stimulations reduce nociceptive interference and thus improve postural control. [Copyright &y& Elsevier]

The optimal treatment of primary mediastinal large B-cell lymphoma (PMLBCL) is still undefined. In the absence of randomised studies, we retrospectively analysed: (a) the effectiveness of two chemotherapy regimens (CHOP vs MACOP-B/VACOP-B) in complete remission (CR) achievement and event-free survival (EFS) and (b) the role of mediastinal involved-field radiotherapy (IF-RT) as consolidation. From 1982 to 1999, 138 consecutive patients affected by PMLBCL were treated in 13 Italian institutions with CHOP (43) or MACOP-B/VACOP-B (95). The two groups of patients were similar as regard to age, gender, presence of bulky mediastinal mass, pleural effusion, stage and international prognostic indexes category of risk. Overall, 75.5% of patients in CR received IF-RT as consolidation. Complete remission was 51.1% in the CHOP group and 80% in MACOP-B/VACOP-B (P<0.001). Relapse occurred in 22.7% of CHOP- and in 9.2% of MACOP-B/VACOP-B-treated patients (n.s.). Event-free patients were 39.5% in CHOP and 75.7% in the MACOP-B/VACOP-B group (P<0.001). The addition of IF-RT as consolidation improved the outcome, irrespectively of the type of chemotherapy (P=0.04). At a multivariate analysis, achievement of CR (P<0.0001) and type of CT (MACOP-B/VACOP-B) retained the significance for OS (P=0.008) and EFS (P=0.03). In our experience, MACOP-B/VACOP-B appears to positively influence OS and EFS in patients affected by PMLBCL, as compared to CHOP. Consolidation IF-RT on mediastinum further improves the outcome of CR patients.British Journal of Cancer (2004) 90, 372-376. doi:10.1038/sj.bjc.6601460 www.bjcancer.com [ABSTRACT FROM AUTHOR]

We investigated the feasibility and activity of an intensified dose-dense ABVD (dd-ABVD) regimen in patients with early-stage unfavorable Hodgkin lymphoma (HL). This prospective, multicenter, phase II study enrolled 96 patients with newly diagnosed, unfavorable stage I or II classical HL. The patients received four cycles of dd-ABVD followed by radiotherapy. Interim PET (PET-2) was mandatory after two courses. Primary endpoints were the evaluation of dd-ABVD feasibility and activity (incidence of PET-2 negativity). The feasibility endpoint was achieved with 48/52 (92.3%) patients receiving > 85% of the programmed dose. The mean dose intensity in the overall patient population (n = 96) was 93.7%, and the median duration of dd-ABVD was 85 days (range, 14-115) versus an expected duration of 84 days. PET-2 was available for 92/96 (95.8%) patients, of whom 79 were PET-2 negative (85.9%). In total, 90 (93.8%) patients showed complete response at the end of treatment. With a follow-up of 80.9 months (3.3-103.2), the median progression-free survival (PFS) and overall survival (OS) were not reached. At 84 months, PFS and OS rates were 88.4% and 95.7%, respectively. No evidence for a difference in PFS or OS was observed for PET-2-negative and PET-2-positive patients. Infections were documented in 8.3% and febrile neutropenia in 6.2% of cases. Four patients died: one had alveolitis at cycle 3, one death was unrelated to treatment, and two died from a secondary cancer. dd-ABVD is feasible and demonstrates activity in early-stage unfavorable HL. The predictive role of PET-2 positivity in early-stage unfavorable HL remains controversial. The study was registered in the EudraCT (reference number, 2011-003,191-36) and the ClinicalTrials.gov (reference number, NCT02247869) databases., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The neutrophil to lymphocyte ratio (NLR) and the lymphocyte to monocyte ratio (LMR) can reflect both the myeloid dysfunction and T-cell immune suppression and have prognostic significance., Methods: In 771 newly diagnosed advanced-stage Hodgkin Lymphoma (HL) patients we evaluated the baseline values of NLR and LMR as predictors of clinical outcome. According to the multicenter prospective phase II GITIL-HD0607 trial, all patients received two ABVD courses and if PET-2 negative received four additional ABVD cycles while if PET-2-positive patients were randomized to either BEACOPP escalated (Be) plus BEACOPP baseline (Bb) (4 + 4 courses) or Be + Bb (4 + 4) and Rituximab. PET scans were centrally reviewed by an expert panel by Blinded Independent Central Review., Results: Higher NLR and lower LMR were associated with a PET-2 positivity and failure to achieve long-term disease control, respectively. By univariate and multivariate analysis, large nodal mass (>7 cm), IPS ≥ 3, NLR > 6 were strong independent predictors of early PET-2 response after ABVD. Only NLR > 6 and IPS ≥ 3 were strong independent predictors of outcome at diagnosis; however, when PET-2 status was added, only PET-2-positive status and IPS ≥ 3 were independent predictors of PFS. Focusing on PET-2-negative patients, those with NLR > 6 had an inferior 3-year PFS compared to patients with NLR ≤ 6 (84% vs 89% months, P = .03)., Conclusion: In advanced-stage HL patients treated with a PET-2-driven strategy, IPS ≥ 3 and NLR > 6 are independent predictors of outcome at diagnosis while the presence of large nodal mass, IPS ≥ 3, and NLR > 6 at diagnosis are independent predictors of early ABVD response., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

ᅟ: FDG PET/CT ( 18 F-fluoro-deoxy-glucose positron emission tomography/computed tomography) is a useful tool to image multiple myeloma (MM). However, simple and reproducible reporting criteria are still lacking and there is the need for harmonization. Recently, a group of Italian nuclear medicine experts defined new visual descriptive criteria (Italian Myeloma criteria for Pet Use: IMPeTUs) to standardize FDG PET/CT evaluation in MM patients. The aim of this study was to assess IMPeTUs reproducibility on a large prospective cohort of MM patients., Materials and Methods: Patients affected by symptomatic MM who had performed an FDG PET/CT at baseline (PET0), after induction (PET-AI), and the end of treatment (PET-EoT) were prospectively enrolled in a multicenter trial (EMN02)(NCT01910987; MMY3033). After anonymization, PET images were uploaded in the web platform WIDEN® and hence distributed to five expert nuclear medicine reviewers for a blinded independent central review according to the IMPeTUs criteria. Consensus among reviewers was measured by the percentage of agreement and the Krippendorff's alpha. Furthermore, on a patient-based analysis, the concordance among all the reviewers in terms of positivity or negativity of the FDG PET/CT scan was tested for different thresholds of positivity (Deauville score (DS 2, 3, 4, 5) for the main parameters (bone marrow, focal score, extra-medullary disease)., Results: Eighty-six patients (211 FDG PET/CT scans) were included in this analysis. Median patient age was 58 years (range, 35-66 years), 45% were male, 15% of them were in stage ISS (International Staging System) III, and 42% had high-risk cytogenetics. The percentage agreement was superior to 75% for all the time points, reaching 100% of agreement in assessing the presence skull lesions after therapy. Comparable results were obtained when the agreement analysis was performed using the Krippendorff's alpha coefficient, either in every single time point of scanning (PET0, PET-AI or PET-EoT) or overall for all the scans together. DS proved highly reproducible with the highest reproducibility for score 4., Conclusions: IMPeTUs criteria proved highly reproducible and could therefore be considered as a base for harmonizing PET interpretation in multiple myeloma. A prospective clinical validation of IMPeTUs criteria is underway.

Purpose: To investigate the impact of adding rituximab to intensive chemotherapy with peripheral-blood progenitor cell (PBPC) autograft for high-risk diffuse large B-cell lymphoma (DLB-CL) and follicular lymphoma (FL)., Patients and Methods: Data were collected from 10 centers associated with Gruppo Italiano Terapie Innnovative nei Linfomi for 522 patients with DLB-CL and 223 patients with FL (median age, 47 years) who received the original or a modified high-dose sequential (HDS) chemotherapy regimen. HDS was delivered to 396 patients without (R-) and to 349 patients with (R+) rituximab; 154 (39%) and 178 patients (51%) in the R- and R+ subsets, respectively, underwent HDS for relapsed/refractory disease., Results: A total of 355 R- (90%) and 309 R+ patients (88%) completed the final PBPC autograft. Early treatment-related mortality was 3.3% for R- and 2.8% for R+ (P = not significant). Two parameters significantly influenced the outcome: disease status at HDS, with 5-year overall survival (OS) projections of 69% versus 57% for diagnosis versus refractory/relapsed status, respectively, and rituximab addition, with 5-year OS of 69% versus 60% in the R+ versus R- groups, respectively. In the multivariate analysis, these two variables maintained an independent prognostic value. The marked benefit of rituximab was evident in patients receiving HDS as salvage treatment: the 5-year OS projections for R+ versus R- were, respectively, 64% versus 38%, for patients with refractory disease or early relapse and 71% versus 57%, for patients with late relapse, partial response, or second/third relapse., Conclusion: The results of this large series indicate that rituximab should be included in the current practice of PBPC autograft for DLB-CL and FL.

Single-center experiences have shown that intensified treatments with autologous transplantation are a promising therapeutic strategy for patients with high-risk follicle-center lymphoma (FCL) at diagnosis, whereas data from prospective multicenter trials are still lacking. This paper describes the results of a prospective multicenter study of an intensified purging-free high-dose sequential (i-HDS) chemotherapy schedule with peripheral blood progenitor cell (PBPC) autografting. The main feature of this program is harvesting stem cells after intensified chemotherapeutic debulking, with no ex vivo manipulation of PBPCs. Ninety-two previously untreated patients aged 60 or younger with advanced-stage FCL were enrolled by 20 Italian centers and evaluated on an intention-to-treat basis. i-HDS proved feasible with limited toxicity (87% patients completed the planned treatment schedule). i-HDS led to a complete remission rate of 88%. The projected overall survival and disease-free survival (DFS) were, respectively, 84% and 67% at 4 years. Centralized molecular analysis showed that polymerase chain reaction-negative harvests could be collected in 47% of cases. Following autograft, 65% of molecularly evaluable patients achieved clinical and molecular remission. The projected DFS at 4 years of this subgroup is 85%. This result emphasizes the importance of achieving maximal tumor reduction in these patients. In conclusion, our data show that highly effective intensified treatments can now be routinely offered to young patients with poor-risk FCL even at small institutions, with no need for sophisticated and expensive cell manipulation procedures.

Background: Elderly Hodgkin's disease patients have a poor prognosis. The question arises whether these patients need aggressive treatment or a palliative strategy. So far, as a consequence of the scarcity of trials designed for them, useful information can be obtained only by retrospective analyses., Methods: We retrospectively studied clinical data from 567 patients recorded from 1982 to 1989 in the Piemonte Hodgkin's Disease Register (PHDR). The 65 patients over 65 years of age were compared to younger ones. We analyzed the role of disease independently of confounding variables, mainly inadequacy of staging and/or treatment, comorbidity and toxicity., Results: In the elderly comorbidity was as high as 35%. Forty elderly patients (60%) entered a suboptimal plan with a low degree of aggressivity, which was different from the usual PHDR protocol. Elderly patients also had a high proportion of subsequent protocol interruptions (25%). Chemotherapy dose intensity was negatively affected by advanced age (p < 0.01 after both 3 and 6 courses of chemotherapy). Toxic deaths were significantly higher in elderly patients than in younger ones (14% vs 1%; p < 0.05). CR rates, overall survival (OS), disease-specific survival (DSS) and event free survival (EFS) were all significantly influenced by age (p < 0.01). Relapse-free survival (RFS) in patients achieving CR did not differ according to age class (77% vs 60%; p = ns). RFS was better in elderly patients entering the PHDR protocols than in those following an alternative plan (75% vs 54%; p = 0.04); however, elderly patients treated according to PHDR guidelines showed a higher incidence of toxic deaths than those treated less aggressively (23% vs 8%). The two groups had similar EFS (36% vs 24%; p = ns)., Conclusions: Elderly patients who achieve CR can have good RFS and cure is possible, but the toxic cost of conventional strategies is unacceptable and selected strategies still must be found.

Seventy-one patients with advanced stage diffuse large cell lymphoma were treated with MACOP-B. Sixty-nine per cent of patients achieved a complete response (CR), 10% a partial remission, while 11% had no response and 10% died because of toxicity. The CR rate was adversely affected by immunoblastic type, poor performance status and bone marrow involvement. Two-year survival for all 71 patients was 55% and 2-year disease-free survival (DFS) for the 49 CRs was 73%. Relapses were lower (P less than 0.05) in patients achieving CR in 8 weeks or less (DFS 83% vs. 59%) and in patients without tumor bulk (DFS 87% vs. 54%). Overall toxicity was acceptable with mucositis proving to be the most frequent severe side-effect. However, treatment-related deaths were unacceptably high in patients over 59 years of age (30% vs. 7%). Thus for the elderly MACOP-B is potentially lethal and must be used cautiously. These preliminary results confirm the effectiveness of MACOP-B. The delay of response and/or the presence of tumor bulk may be important prognostic factors in identifying a subset of poor risk patients with a high incidence of relapse.