Vitamin D and SARS-CoV2 infection, severity and mortality: A systematic review and meta-analysis.

To assess the evidence on SARS-CoV2 infection and Covid-19 in relation to deficiency and supplementation of vitamin D, we conducted a systematic review up to April 2021. We summarised data from 38 eligible studies, which presented risk estimates for at least one endpoint, including two RCT and 27 cohort-studies: 205565 patients with information on 25OHD status and 2022 taking vitamin D supplementation with a total of 1197 admitted to the ICU or who needed invasive mechanical ventilation or intubation and hospital stay, and more than 910 Covid-19 deaths. Primary outcomes were severity and mortality and the main aim was to evaluate the association with vitamin D supplementation. Random effects models showed that supplementation was associated with a significant lower risk of both Covid-19 severe disease (SRR 0.38, 95% CI 0.20-0.72, 6 studies) and mortality (SRR 0.35, 95% CI 0.17-0.70, 8 studies). There were no statistically significant dose differences between studies: summary estimates with regular doses remain statistically significant, suggesting that higher doses are not necessary. For patients on vitamin D supplementation, a greater reduction in mortality risk emerged in older individuals and at higher latitudes. Regarding the quality of studies, assessed using the New Castle-Ottawa quality scale, the analysis revealed in most cases no statistically significant differences between low, medium or high quality studies. We found significant associations of vitamin D supplementation with Covid-19, encompassing risks of disease worsening and mortality, especially in seasons characterized by 25OHD deficiency and with not severe patients. Dedicated randomized clinical studies are encouraged to confirm these results.

The Association between Vitamin D and Gut Microbiota: A Systematic Review of Human Studies.

Recent evidence has shown a number of extra-skeletal functions of Vitamin D (VD), primarily involving the immune system. One of these functions is mediated by the modulation of gut microbiota, whose alterations are linked to many diseases. Our purpose is to contribute to the understanding of existing evidence on the association between VD and gastrointestinal microbiota alterations. A systematic review of studies with human subjects has been conducted up to January 2021. We included publications reporting the association between gut microbiota and VD, including VD supplementation, dietary VD intake and/or level of 25(OH)D. We identified 25 studies: 14 were interventional and 11, observational. VD supplementation was found to be associated with a significant change in microbiome composition, in particular of Firmicutes, Actinobacteria and Bacteroidetes phyla. Furthermore, Firmicutes were found to be correlated with serum VD. Concerning alpha and beta diversity, a high nutritional intake of VD seems to induce a shift in bacterial composition and/or affects the species' richness. Veillonellaceae and Oscillospiraceae families, in the Firmicutes phylum, more frequently decreased with both increasing levels of 25(OH)D and vitamin D supplementation. We found evidence of an association, even though the studies are substantially heterogeneous and have some limitations, resulting sometimes in conflicting results. To further understand the role of VD on the modulation of the gastrointestinal microbiota, future research should be geared toward well-designed animal-based studies or larger randomized controlled trials (RCTs).

Vitamin D Supplementation and Cancer Mortality: Narrative Review of Observational Studies and Clinical Trials.

Several studies have investigated the beneficial effects of vitamin D on survival of cancer patients. Overall evidence has been accumulating with contrasting results. This paper aims at narratively reviewing the existing articles examining the link between vitamin D supplementation and cancer mortality. We performed two distinct searches to identify observational (ObS) studies and randomized clinical trials (RCTs) of vitamin D supplementation (VDS) in cancer patients and cohorts of general population, which included cancer mortality as an outcome. Published reports were gathered until March 2021. We identified 25 papers published between 2003 and 2020, including n. 8 RCTs on cancer patients, n. 8 population RCTs and n. 9 ObS studies. There was some evidence that the use of VDS in cancer patients could improve cancer survival, but no significant effect was found in population RCTs. Some ObS studies reported evidence that VDS was associated with a longer survival among cancer patients, and only one study found an opposite effect. The findings do not allow conclusive answers. VDS may have the potential as treatment to improve survival in cancer patients, but further investigations are warranted. We strongly support investment in well-designed and sufficiently powered RCTs to fully evaluate this association.

Searching for Evidence to Support the Use of Ginger in the Prevention of Chemotherapy-Induced Nausea and Vomiting.

Patients with cancer frequently use dietary supplementation and herbal therapies to control symptoms of disease and adverse effects of cancer therapy. Despite the widespread use of dietary supplementation and herbal therapies in oncology, robust scientific evidence in this area is lacking. Not only do these products need to be tested in large and well-designed observational or randomized studies, but their manufacturing process must be improved to achieve higher levels of standardization in product quality. Ginger is frequently used to counteract chemotherapy-induced nausea and vomiting (CINV), and some suggestions that it might be effective against CINV come from randomized and/or crossover clinical trials. However, several limitations in the methods of these studies limit their power and generalizability. The authors are conducting a randomized, double-blind study with a large sample size and homogeneous inclusion criteria in order to evaluate the efficacy of a well-standardized ginger extract in reducing nausea in patients with cancer. The widespread use of standardized herbal therapies and natural components among patients requires that scientific and rigorous research strategies are applied in this field to guide the physicians and the patients in safer use.

Voltage-gated sodium channel polymorphisms play a pivotal role in the development of oxaliplatin-induced peripheral neurotoxicity: results from a prospective multicenter study.

BACKGROUND: The current prospective, multicenter study sought to identify single nucleotide polymorphisms of voltage-gated sodium channels (SCNAs) genes that might confer susceptibility to an increased incidence and severity of oxaliplatin-induced peripheral neuropathy (OXAIPN) in patients treated with either leucovorin, 5-fluorouracil, and oxaliplatin (FOLFOX) or oxaliplatin plus capecitabine (XELOX) for colorectal cancer (CRC). METHODS: A total of 200 patients with CRC were genotyped with real-time polymerase chain reaction using locked nucleic acid hydrolysis probes or allele-specific primers. All patients had received oxaliplatin-based chemotherapy, either in the adjuvant or metastatic setting. The incidence and severity of cumulative OXAIPN was graded using the clinical version of the Total Neuropathy Score and the neurosensory National Cancer Institute Common Toxicity Criteria (version 3.0). The incidence of acute OXAIPN was assessed using a descriptive questionnaire (yes/no response format) at each clinical evaluation. Acute OXAIPN was present in 169 of 200 patients (84.5%), whereas after treatment discontinuation, the cumulative/chronic form of neurotoxicity occurred in 145 of 200 patients (72.5%). RESULTS: In the logistic regression analysis adjusted for confounding factors, the overdominant model (CT vs CC + TT) of 2 single nucleotide polymorphisms (ie, SCN4A-rs2302237 and SCN10A-rs1263292) emerged as being significantly associated with an increased incidence of acute OXAIPN (rs2302237: odds ratio of 2.62 [95% confidence interval (95% CI), 1.15-6.00]; P = .019; and rs12632942: OR of 0.39 [95% CI, 0.17-0.88]; P = .023). However, only SCN4A-rs2302237 emerged as also being predictive of the clinical severity of acute OXAIPN (OR, 2.50 [95% CI, 1.35-4.63]; P = .0029) and the occurrence of cumulative/chronic OXAIPN (OR, 2.47 [95% CI, 1.04-5.85]; P = .037). CONCLUSIONS: The results of the current study provide evidence to support a causal relationship between SCNA polymorphisms and OXAIPN. However, further studies from independent groups are warranted to confirm these results.

Chemotherapy-induced anemia and oncologist perception on treatment: results of a web-based survey.

AIMS AND BACKGROUND: Anemia prevalence and incidence in chemotherapy-treated patients is high. Erythropoiesis-stimulating agents (ESAs) are frequently employed in the management of chemotherapy-induced anemia. However, other treatments such as red blood transfusion or iron supplementation are normally used. Recent international guidelines raised some concern about ESAs employment with a possible impact in chemotherapy-induced anemia management and changes in clinical practice behavior. METHODS: To evaluate opinions about chemotherapy-induced anemia clinical management preference, the Associazione Italiana Oncologia Medica (AIOM) Lombardy section coordinators sent via email a 12-item questionnaire about their knowledge on CIA and usual therapeutic strategies to manage this adverse event to AIOM Lombardy onco-hematologist members. RESULTS: From January 2011 to March 2011, 81 questionnaires were collected with an approximated share of 30%. The survey was completed mainly by oncologists (91%) aged 35-50 years (50%). Chemotherapy-induced anemia was considered to have clinical impact in changing cancer therapeutic strategy by nearly 60% of the respondents. ESAs were administered largely (80%) with concomitant iron supplementation in 52%; 38% jointly used blood transfusion as part of the therapy. Nearly 20% of those who replied correctly employed transferrin saturation levels as a marker to guide iron supplementation. Physician prescribers strictly followed the guidelines to start and stop ESAs even if 14% were negatively influenced by new ASCO recommendations. ESA biosimilars were considered future substitutes of originators in 45% of the cases. CONCLUSIONS: Chemotherapy-induced anemia was perceived as an adverse event with a mild impact on clinical practice. ESAs were largely employed, however the number of transfusions and lack of employment of markers of iron depletion suggested that adherence to guidelines could be theoretically met but with some discordances regarding the most appropriate strategies in daily clinical practice.

Efficacy of treatment with irinotecan and oxaliplatin combination in FU-resistant metastatic colorectal cancer patients.

OBJECTIVES: As single agents, irinotecan and oxaliplatin are active in colorectal cancer after fluorouracil (FU)-containing regimen failure. Their synergistic activity and non-overlapping toxicity profile are well documented, but more data are needed to explore their exact sequence. The aim of this study was to evaluate the activity and tolerability of irinotecan followed by oxaliplatin in patients with FU-resistant colorectal cancer. METHODS: FU resistance was defined as disease progression during or within 6 months of discontinuing first-line or adjuvant FU/leucovorin chemotherapy. The study treatment consisted of irinotecan 150 mg/m(2) on days 1 and 8 followed by oxaliplatin 85 mg/m(2) on day 1 every 3 weeks. In order to improve the safety profile, we changed the schedule during the study to irinotecan 300 mg/m(2) on day 1 and oxaliplatin 85 mg/m(2) on day 2 every 3 weeks. RESULTS: Of 54 patients treated, the 45 patients with measurable disease were assessed in the efficacy analysis, whereas all patients receiving at least one cycle were evaluated in the safety analysis. Of the patients assessed for efficacy analysis, 19 cases received the first schedule and 26 patients received the second schedule. Twenty-two patients (49%) responded, 10 of the first schedule and 12 of the second schedule group. Stable disease was observed in 35% of all patients. The median response duration was 6.5 months (range 3-10), the median time to progression was 8 months (range 6-10), and the overall survival was 15 months (10-26+). The NCI-CTC grade 3 side effects documented in all of the treated patients were: nausea/vomiting (11%), diarrhea (18%), and neutropenia (7%); grade 4 diarrhea was observed in 2% of patients. CONCLUSION: The combination of irinotecan followed by oxaliplatin combination is well tolerated and highly active in FU-resistant metastatic colorectal cancer patients.