Restriction in meal timing has emerged as a promising dietary approach for the management of obesity and dysmetabolic diseases. The present systematic review and meta-analysis summarized the most ...recent evidence on the effect of time-restricted feeding (TRF) on weight-loss and cardiometabolic variables in comparison with unrestricted-time regimens. Studies involving TRF regimen were systematically searched up to January 2019. Effect size was expressed as weighted mean difference (WMD) and 95% confidence intervals (CI). A total of 11 studies, 5 randomized controlled trials and 6 observational, were included. All selected studies had a control group without time restriction; hours of fasting ranged from 12-h until 20-h and study duration from 4 to 8-weeks. Most studies involved the Ramadan fasting. TRF determined a greater weight-loss than control regimens (11 studies,
n
= 485 subjects) (WMD: −1.07 kg, 95%CI: −1.74 to −0.40;
p
= 0.002; I
2
= 56.2%), unrelated to study design. The subgroup analysis showed an inverse association between TRF and fat free mass in observational studies (WMD: −1.33 kg, 95%CI: −2.55 to −0.11;
p
= 0.03; I
2
= 0%). An overall significant reduction in fasting glucose concentrations was observed with TRF regimens (7 studies,
n =
363 subjects) (WMD: −1.71 mg/dL, 95%CI: −3.20 to −0.21;
p
= 0.03; I
2
= 0%), above all in trials (WMD:-2.45 mg/dL, 95%CI: −4.72 to −0.17; p = 0.03; I
2
= 0%). No between-group differences in the other variables were found. TRF regimens achieved a superior effect in promoting weight-loss and reducing fasting glucose compared to approaches with unrestricted time in meal consumption. However, long-term and well-designed trials are needed to draw definitive conclusions.
This systematic review and meta-analysis summarized the most recent evidence on the efficacy of intermittent energy restriction (IER) versus continuous energy restriction on weight-loss, body ...composition, blood pressure and other cardiometabolic risk factors.
Randomized controlled trials were systematically searched from MEDLINE, Cochrane Library, TRIP databases, EMBASE and CINAHL until May 2018. Effect sizes were expressed as weighted mean difference (WMD) and 95% confidence intervals (CI).
Eleven trials were included (duration range 8-24 weeks). All selected intermittent regimens provided ≤ 25% of daily energy needs on "fast" days but differed for type of regimen (5:2 or other regimens) and/or dietary instructions given on the "feed" days (ad libitum energy versus balanced energy consumption). The intermittent approach determined a comparable weight-loss (WMD: - 0.61 kg; 95% CI - 1.70 to 0.47; p = 0.87) or percent weight loss (WMD: - 0.38%, - 1.16 to 0.40; p = 0.34) when compared to the continuous approach. A slight reduction in fasting insulin concentrations was evident with IER regimens (WMD = - 0.89 µU/mL; - 1.56 to - 0.22; p = 0.009), but the clinical relevance of this result is uncertain. No between-arms differences in the other variables were found.
Both intermittent and continuous energy restriction achieved a comparable effect in promoting weight-loss and metabolic improvements. Long-term trials are needed to draw definitive conclusions.
Objective
Neurological symptoms of COVID-19 patients have been recently described. However, no comprehensive data have been reported on pre-existing neurological comorbidities and COVID-19. This ...study aims at evaluating the prevalence of neurological comorbidities, and their association with COVID-19 severity.
Methods
We evaluated all consecutive patients admitted to the Emergency Room (ER) of our hospital between the 3rd March and the 14th April 2020, and diagnosed with COVID-19. Data on neurological and non-neurological diseases were extracted, as well as data on demographic characteristics and on severity degree of COVID-19. The prevalence of neurological comorbidities was calculated, and multivariate binary logistic regression analyses were used to estimate the association between neurological diseases and COVID-19 severity.
Results
We included 344 patients. Neurological comorbidities accounted for 22.4% of cases, with cerebrovascular diseases and cognitive impairment being the most frequent. Neurological comorbidity resulted independently associated with severe COVID-19 (OR 2.305;
p
= 0.012), as well as male gender (
p
= 0.001), older age (
p
= 0.001), neoplastic diseases (
p
= 0.039), and arterial hypertension (
p
= 0.045). When neurological comorbidity was associated with non-neurological comorbidities, the OR for severe COVID-19 rose to 7.394 (
p
= 0.005). Neurological patients, in particular cerebrovascular and cognitively impaired ones, received more respiratory support indication.
Conclusion
Neurological comorbidities represent a significant determinant of COVID-19 severity, deserving a thorough evaluation since the earliest phases of infection. The vulnerability of patients affected by neurological diseases should suggest a greater attention in targeting this population for proactive viral screening.
The combination of bortezomib-melphalan-prednisone (VMP) is a new standard of care for newly diagnosed multiple myeloma. This phase III study examined the efficacy of the four-drug combination of ...bortezomib-melphalan-prednisone-thalidomide (VMPT) followed by maintenance with bortezomib-thalidomide (VMPT-VT) compared with VMP treatment alone in untreated multiple myeloma patients who are ineligible for autologous stem-cell transplantation.
A total of 511 patients were randomly assigned to receive nine cycles of VMPT followed by continuous VT as maintenance, or nine cycles of VMP at the same doses with no additional therapy. The primary end point was progression-free survival.
The 3-year estimates of progression-free survival were 56% in patients receiving VMPT-VT and 41% in those receiving VMP (hazard ratio HR, 0.67; 95% CI, 0.50 to 0.90; P = .008). At 3 years, the cumulative proportions of patients who did not go on to the next therapy were 72% with VMPT-VT and 60% with VMP (HR, 0.58; 95% CI, 0.50 to 0.90; P = .007). Complete response rates were 38% in the VMPT-VT group and 24% in the VMP group (P < .001). The 3-year overall survival was 89% with VMPT-VT and 87% with VMP (HR, 0.92; 95% CI, 0.53 to 1.60; P = .77). Grade 3 to 4 neutropenia (38% v 28%; P = .02), cardiologic events (10% v 5%; P = .04), and thromboembolic events (5% v 2%; P = .08) were more frequent among patients assigned to the VMPT-VT group than among those assigned to the VMP group; treatment-related deaths were 4% with VMPT-VT and 3% with VMP.
VMPT followed by VT as maintenance was superior to VMP alone in patients with multiple myeloma who are ineligible for autologous stem-cell transplantation.
This study was undertaken to assess the short-term outcomes of neoadjuvant short-course radiation therapy (SCRT) followed by transanal endoscopic microsurgery (TEM) for T1-T2 N0 extraperitoneal ...rectal cancer. Recent studies suggest that neoadjuvant radiation therapy followed by TEM is safe and has results similar to those with abdominal rectal resection for the treatment of extraperitoneal early rectal cancer.
We planned a prospective pilot study including 25 consecutive patients with extraperitoneal T1-T2 N0 M0 rectal adenocarcinoma undergoing SCRT followed by TEM 4 to 10 weeks later (SCRT-TEM). Safety, efficacy, and acceptability of this treatment modality were compared with historical groups of patients with similar rectal cancer stage and treated with long-course radiation therapy (LCRT) followed by TEM (LCRT-TEM), TEM alone, or laparoscopic rectal resection with total mesorectal excision (TME) at our institution.
The study was interrupted after 14 patients underwent SCRT of 25 Gy in 5 fractions followed by TEM. Median time between SCRT and TEM was 7 weeks (range: 4-10 weeks). Although no preoperative complications occurred, rectal suture dehiscence was observed in 7 patients (50%) at 4 weeks follow-up, associated with an enterocutaneous fistula in the sacral area in 2 cases. One patient required a colostomy. Quality of life at 1-month follow-up, according to European Organization for Research and Treatment of Cancer QLQ-C30 survey score, was significantly worse in SCRT-TEM patients than in LCRT-TEM patients (P=.0277) or TEM patients (P=.0004), whereas no differences were observed with TME patients (P=.604). At a median follow-up of 10 months (range: 6-26 months), we observed 1 (7%) local recurrence at 6 months that was treated with abdominoperineal resection.
SCRT followed by TEM for T1-T2 N0 rectal cancer is burdened by a high rate of painful dehiscence of the suture line and enterocutaneous fistula, compared to TEM alone and TEM following LCRT, which forced us to stop the study.
Summary Background Up to 40% of elderly patients with untreated diffuse large B-cell lymphoma (DLBCL) given a regimen of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone every ...21 days (R-CHOP21) relapse or develop refractory disease. Lenalidomide has high activity in relapsed or refractory aggressive B-cell lymphomas. In phase 2 of the REAL07 trial, we aimed to establish the safety and efficacy of the combination of lenalidomide and R-CHOP21 in elderly patients with untreated DLBCL. Methods REAL07 was an open-label, multicentre trial that was done in 13 centres in Italy and one in Germany. Eligible patients were aged 60–80 years; had newly diagnosed, untreated, CD20-positive, Ann Arbor stage II–IV DLBCL or grade 3b follicular lymphoma; had an Eastern Cooperative Oncology Group performance status of 0–2; had an International Prognostic Index (IPI) risk of low-intermediate, intermediate-high, or high; and were fit according to comprehensive geriatric assessment. Participants were to receive 15 mg oral lenalidomide on days 1–14 of six 21-day cycles, and standard doses of R-CHOP21 chemotherapy (375 mg/m2 intravenous rituximab, 750 mg/m2 intravenous cyclophosphamide, 50 mg/m2 intravenous doxorubicin, and 1·4 mg/m2 intravenous vincristine on day 1, and 40 mg/m2 oral prednisone on days 1–5). The primary endpoint was frequency of overall response (complete response CR and partial response PR), which was assessed by18 F-fluorodeoxyglucose (18 F-FDG) PET at the end of the treatment. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00907348. Findings 49 patients were included in phase 2: nine had been enrolled into phase 1 between Oct 23, 2008, and June 4, 2009, and had received the maximum tolerated dose of 15 mg lenalidomide; and 40 were enrolled into phase 2 between April 28, 2010, and June 3, 2011. 45 patients (92%, 95% CI 81–97) achieved a response (42 86% CR; three 6% PR). Three patients (6%) did not respond and one (2%) died for reasons unrelated to treatment or disease. 277 (94%) of 294 planned cycles of lenalidomide and R-CHOP21 were completed. Grade 3–4 neutropenia was reported in 87 cycles (31%), grade 3–4 leukopenia in 77 (28%), and grade 3–4 thrombocytopenia in 35 (13%). No grade 4 non-haematological adverse events were reported. No patients died during the study as a result of toxic effects. Interpretation Lenalidomide with R-CHOP21 is effective and safe in elderly patients with untreated DLBCL. Funding Fondazione Italiana Linfomi and Celgene.
The available data on the natural history of pheochromocytomas and paragangliomas after radical surgery are heterogeneous and discordant. The aim of our retrospective multicenter study was to find ...predictors of recurrence in patients with pheochromocytomas and sympathetic paragangliomas submitted to radical surgery in Piedmont (a region in northwest Italy). We collected data from 242 patients diagnosed between 1990 and 2016. Forty-two patients (17.4%) had disease recurrence. Multivariate analysis showed that genetic mutation (HR = 3.62; 95% CI 1.44-9.13; p = 0.006), younger age (HR = 0.97; 95% CI 0.95-0.99; p = 0.031) and larger tumor size (HR = 1.01; 95% CI 1.00-1.02; p = 0.015) were independently associated with a higher recurrence risk of pheochromocytoma and paraganglioma; in pheochromocytomas, genetic mutation (HR = 3.4; 95% CI 1.00-11.48; p = 0.049), younger age (HR = 0.97; 95% CI 0.94-0.99; p = 0.02), higher tumor size (HR = 1.01; 95% CI 1.00-1.03; p = 0.043) and PASS value (HR = 1.16; 95% CI 1.03-1.3; p = 0.011) were associated with recurrence. Moreover, tumor size was the only predictor of metastatic pheochromocytoma and paraganglioma (HR = 4.6; 95% CI 1.4-15.0; p = 0.012); tumor size (HR = 3.93; 95% CI 1.2-16.4; p = 0.026) and PASS value (HR = 1.27; 95% CI 1.06-1.53; p = 0.007) were predictors of metastatic pheochromocytoma. In conclusion, our findings suggest that the recurrence of pheochromocytoma and sympathetic paraganglioma develops more frequently in younger subjects, patients with a family history of chromaffin tissue neoplasms, mutations in susceptibility genes, larger tumors and higher values of PASS. We recommend genetic testing in all patients with PPGL and strict follow-up at least on an annual basis.
Background.
Whether or not hypovitaminosis D can influence the prognosis of cancer patients and whether or not vitamin D (vitD) supplementation improves outcome remain controversial.
Design.
Studies ...evaluating the prognostic role of vitD and vitD receptor (VDR) in cancer patients and trials evaluating the efficacy of vitD administration on patient outcome were identified by a search of MEDLINE, EMBASE, ISI Web of Knowledge, and the Cochrane Library through June 2010.
Results.
Twenty‐five studies were included. A negative prognostic role for low serum vitD level was observed in five cohort studies including patients with breast cancer (one study), colon cancer (two studies), prostate cancer (one study), and melanoma (one study), but not in two studies on non‐small cell lung cancer and one study on breast cancer. Three of four studies showed that VDR+ tumors carry a better prognosis than VDR− tumors, whereas VDR polymorphisms were significantly associated with prognosis in five of 10 studies. A significant interaction between serum vitD level and VDR polymorphism was observed in one study. Three randomized trials involving advanced prostate cancer patients explored the prognostic role of vitD supplementation. A meta‐analysis of these trials showed no effect on survival (pooled risk ratio, 1.07; 95% confidence interval, CI, 0.93–1.23), with strong heterogeneity among studies.
Conclusion.
Hypovitaminosis D seems to be associated with a worse prognosis in some cancers, but vitD supplementation failed to demonstrate a benefit in prostate cancer patients. The currently available evidence is insufficient to recommend vitD supplementation in cancer patients in clinical practice.
摘要
背景。维生素D（vitD）缺乏症是否影响癌症患者的预后，抑或补充vitD能否改善疾病转归，目前仍存在争议。
设计：为评估vitD状态与vitD受体（VDR）对癌症患者的预后意义以及补充vitD对患者的生存的影响，在MEDLINE、EMBASE、ISI Web of Knowledge和CochraneLibrary数据库中对2010年6月之前的研究资料进行检索。
结果：共检索到符合条件的研究25项，有5项研究认为血清低水平vitD是患者的预后不良的因素（其中包括乳腺癌1项、结肠癌2项、前列腺癌1项、黑色素瘤1项），但在2项非小细胞肺癌和1项乳腺癌的研究中得出了相反的结论。在4项关于vitD受体的研究中，有3项显示vitD受体阳性的肿瘤预后好于vitD受体阴性；然而，在10项关于vitD受体多态性的研究中，有5项显示vitD受体多态性与预后显著相关。有1项研究显示vitD血清水平与VDR多态性之间存在相互影响。3项关于晚期前列腺癌的随机研究探究了补充vitD对患者预后所产生的作用，对这3项研究进行meta分析显示补充vitD不影响晚期前列腺癌患者的生存结果（风险比1.07；95%CI 0.93~1.23），但各研究间存在较大差异。
结论。vitD缺乏症似乎与某些癌症的预后不良相关，但补充vitD却未显示出对前列腺癌症患者带来益处。现有证据不足以推荐补充vitD用于临床实践中的癌症患者。
Whether or not hypovitaminosis D can influence the prognosis of cancer patients and whether or not vitamin D supplementation improves outcome were examined through a literature review. It was concluded that the currently available evidence is insufficient to recommend vitamin D supplementation in cancer patients in clinical practice.
Thalidomide and bortezomib are extensively used to treat elderly myeloma patients. In these patients, treatment-related side effects are frequent and full drug doses difficult to tolerate. We ...retrospectively analyzed data from 1435 elderly patients enrolled in 4 European phase III trials including thalidomide and/or bortezomib. After a median follow up of 33 months (95%CI: 10-56 months), 513 of 1435 patients (36%) died; median overall survival was 50 months (95%CI: 46-60 months). The risk of death was increased in patients aged 75 years or over (HR 1.44, 95%CI: 1.20-1.72; P<0.001), in patients with renal failure (HR 2.02, 95%CI: 1.51-2.70; P<0.001), in those who experienced grade 3-4 infections, cardiac or gastrointestinal adverse events during treatment (HR 2.53, 95%CI: 1.75-3.64; P<0.001) and in those who required drug discontinuation due to adverse events (HR 1.67, 95%CI; 1.12-2.51; P=0.01). This increased risk was restricted to the first six months after occurrence of adverse events or drug discontinuation and declined over time. More intensive approaches, such as the combination of bortezomib-thalidomide, negatively affected outcome. Bortezomib-based combinations may overcome the negative impact of renal failure. Age 75 years or over or renal failure at presentation, occurrence of infections, cardiac or gastrointestinal adverse events negatively affected survival. A detailed geriatric assessment, organ evaluation and less intense individualized approaches are suggested in elderly unfit subjects.
Summary
The prognostic role of TP53 disruption has been established in diffuse large B‐cell lymphoma (DLBCL). Aim of this analysis was to correlate TP53 mutations by Sanger sequencing, cell of origin ...(COO) profile by Lymph2Cx panel on the NanoString platform and MYC, BCL2 and BCL6 overexpression or re‐arrangements by immunohistochemistry (IHC) and fluorescent in‐situ hybridization (FISH), with outcome in DLBCL patients enrolled into the FIL‐DLCL04 trial (NCT00499018). One hundred and twenty‐five DLBCL patients with tumour block available were analyzed. TP53 was mutated in 11/125 (9%) cases; 60/125 patients received high‐dose chemoimmunotherapy up‐front, as for the randomization arm; COO was reported in 88 patients: 48 germinal centre B‐cell like, 25 activated B‐cell like and 17 unclassified; 26 patients were double expressors in IHC and 11 double hit in FISH. After a median follow‐up of 72 months, five‐year failure‐free survival (FFS) for TP53 mutated versus wild‐type was 24% and 72%, and five‐year overall survival (OS) was 34% and 83%, respectively. Adjusted hazard ratio (HR) was 2·28 95% confidence interval (CI) 0·89–5·86, p = 0·086 and 4·05 (95% CI 1·37–11·97, p = 0·011) for FFS and OS, respectively. In this series of young DLBCL patients, TP53 gene mutation identified a poor prognosis subgroup, regardless of treatment and other biological markers.
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