There were no statistically or clinically significant differences between immediate and early loading of dental implants with regard to peri-implant bone and soft-tissue levels as evaluated in the present study.
Background:Dihydropyrimidine dehydrogenase (DPD) catabolises ∼85% of the administered dose of fluoropyrimidines. Functional DPYD gene variants cause reduced/abrogated DPD activity. DPYD variants analysis may help for defining individual patients’ risk of fluoropyrimidine-related severe toxicity.Methods:The TOSCA Italian randomised trial enrolled colon cancer patients for 3 or 6 months of either FOLFOX-4 or XELOX adjuvant chemotherapy. In an ancillary pharmacogenetic study, 10 DPYD variants (*2A rs3918290 G>A, *13 rs55886062 T>G, rs67376798 A>T, *4 rs1801158 G>A, *5 rs1801159 A>G, *6 rs1801160 G>A, *9A rs1801265 T>C, rs2297595 A>G, rs17376848 T>C, and rs75017182 C>G), were retrospectively tested for associations with ⩾grade 3 fluoropyrimidine-related adverse events (FAEs). An association analysis and a time-to-toxicity (TTT) analysis were planned. To adjust for multiple testing, the Benjamini and Hochberg’s False Discovery Rate (FDR) procedure was used.Results:FAEs occurred in 194 out of 508 assessable patients (38.2%). In the association analysis, FAEs occurred more frequently in *6 rs1801160 A allele carriers (FDR=0.0083). At multivariate TTT analysis, significant associations were found for *6 rs1801160 A allele carriers (FDR<0.0001), *2A rs3918290 A allele carriers (FDR<0.0001), and rs2297595 GG genotype carriers (FDR=0.0014). Neutropenia was the most common FAEs (28.5%). *6 rs1801160 (FDR<0.0001), and *2A rs3918290 (FDR=0.0004) variant alleles were significantly associated with time to neutropenia.Conclusions:This study adds evidence on the role of DPYD pharmacogenetics for safety of patients undergoing fluoropyrimidine-based chemotherapy.
Introduction. Maxillary sinus surgery is a reliable and predictable treatment option for the prosthetic rehabilitation of the atrophic maxilla. Nevertheless, these interventions are not riskless of postoperative complications with respect to implant positioning in pristine bone. Aim. The aim of this paper is to report the results of a clinical consensus of experts (periodontists, implantologists, maxillofacial surgeons, ENT, and microbiology specialists) on several clinical questions and to give clinical recommendations on how to prevent, diagnose, and treat postoperative infections. Materials and Methods. A panel of experts in different fields of dentistry and medicine, after having reviewed the available literature on the topic and taking into account their long-standing clinical experience, gave their response to a series of clinical questions and reached a consensus. Results and Conclusion. The incidence of postop infections is relatively low (2%–5.6%). A multidisciplinary approach is advisable. A list of clinical recommendation are given.
PURPOSE: As oxaliplatin results in cumulative neurotoxicity, reducing treatment duration without loss of efficacy would benefit patients and healthcare providers. PATIENTS AND METHODS: Four of the six studies in the International Duration of Adjuvant Chemotherapy (IDEA) collaboration included patients with high-risk stage II colon and rectal cancers. Patients were treated (clinician and/or patient choice) with either fluorouracil, leucovorin, and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CAPOX) and randomly assigned to receive 3- or 6-month treatment. The primary end point is disease-free survival (DFS), and noninferiority of 3-month treatment was defined as a hazard ratio (HR) of < 1.2- v 6-month arm. To detect this with 80% power at a one-sided type one error rate of 0.10, a total of 542 DFS events were required. RESULTS: 3,273 eligible patients were randomly assigned to either 3- or 6-month treatment with 62% receiving CAPOX and 38% FOLFOX. There were 553 DFS events. Five-year DFS was 80.7% and 83.9% for 3-month and 6-month treatment, respectively (HR, 1.17; 80% CI, 1.05 to 1.31; P [for noninferiority] .39). This crossed the noninferiority limit of 1.2. As in the IDEA stage III analysis, the duration effect appeared dependent on the chemotherapy regimen although a test of interaction was negative. HR for CAPOX was 1.02 (80% CI, 0.88 to 1.17), and HR for FOLFOX was 1.41 (80% CI, 1.18 to 1.68). CONCLUSION: Although noninferiority has not been demonstrated in the overall population, the convenience, reduced toxicity, and cost of 3-month adjuvant CAPOX suggest it as a potential option for high-risk stage II colon cancer if oxaliplatin-based chemotherapy is suitable. The relative contribution of the factors used to define high-risk stage II disease needs better understanding.
When implants are placed immediately after tooth extraction, I-BP may represent a useful diagnostic parameter in choosing the most appropriate grafting procedure (IG versus IEG). In clinical cases in which the distance between implant surface and the buccal plate is <4 mm, the combination of internal and external grafting (IEG) is recommended to maintain the volume and the contour of the ridge and achieve a successful esthetic outcome.
The aim of this study was to examine the relationship between visual field (VF) loss, vision-related quality of life (QoL) and glaucoma-related symptoms in a large cohort of primary open angle glaucoma (POAG) patients. POAG patients with or without VF defects or “glaucoma suspect” patients were considered eligible. QoL was assessed using the validated versions of the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and glaucoma-related symptoms were assessed using the Glaucoma Symptom Scale (GSS). Patients were classified as having VF damage in one eye (VFD-1), both eyes (VFD-2), or neither eye (VFD-0). 3227 patients were enrolled and 2940 were eligible for the analysis. 13.4% of patients were classified in the VFD-0, 23.7% in the VFD-1, and 62.9% in the VFD-2 group. GSS visual symptoms domain (Func-4) and GSS non-visual symptoms domain (Symp-6) scores were similar for the VFD-0 and VFD-1 groups (p = 0.133 and p = 0.834 for Func-4 and Symp-6, respectively). VFD-0 group had higher scores than VFD-2 both in Func-4 (p < 0.001) and Symp-6 domains (p = 0.035). Regarding the NEI-VFQ-25, our data demonstrated that bilateral VF defects are associated with vision-related QoL deterioration, irrespective of visual acuity.
Background In patients with end stage renal disease and atrial fibrillation (AF), undergoing chronic dialysis, direct oral agents are contraindicated and warfarin does not fully prevent embolic events while increasing the bleeding risk. The high hemorrhagic risk represents the main problem in this population. Aim of the study was to estimate the safety and efficacy for thromboembolic prevention of left atrial appendage (LAA) occlusion in a cohort of dialysis patients with AF and high hemorrhagic risk. Methods Ninety-two dialysis patients with AF who underwent LAA occlusion were recruited. For comparative purposes, two cohorts of dialysis patients with AF, one taking warfarin (oral anticoagulant therapy, OAT cohort, n = 114) and the other not taking any OAT (no-therapy cohort, n = 148) were included in the study. Primary endpoints were (1) incidence of peri-procedural complications, (2) incidence of 2-year thromboembolic and hemorrhagic events, (3) mortality at 2 years. In order to evaluate the effect of the LAA occlusion on the endpoints with respect to the OAT and No-therapy cohorts, a multivariable Cox regression model was applied adjusted for possible confounding factors. Results The device was successfully implanted in 100% of cases. Two major peri-procedural complications were reported. No thromboembolic events occurred at 2-year follow-up. The adjusted multivariable Cox regression model showed no difference in bleeding risk in the OAT compared to the LAA occlusion cohort in the first 3 months of follow-up [HR 1.65 (95% CI 0.43-6.33)], when most of patients were taking two antiplatelet drugs. In the following 21 months the bleeding incidence became higher in OAT patients [HR 6.48 (95% CI 1.32-31.72)]. Overall mortality was greater in both the OAT [HR 2.76 (95% CI 1.31-5.86)] and No-Therapy [HR 3.09 (95% CI 1.59-5.98)] cohorts compared to LAA occlusion patients. Conclusions The study could open the way to a non-pharmacological option for thromboembolic protection in dialysis patients with AF and high bleeding risk.
We investigated 17 polymorphisms in 11 genes (TS, MTHFR, ERCC1, XRCC1, XRCC3, XPD, GSTT1, GSTP1, GSTM1, ABCC1, ABCC2) for their association with the toxicity of fluoropyrimidines and oxaliplatin in colorectal cancer patients enrolled in a prospective randomized trial of adjuvant chemotherapy. The TOSCA Italian adjuvant trial was conducted in high-risk stage II–III colorectal cancer patients treated with 6 or 3 months of either FOLFOX-4 or XELOX adjuvant chemotherapy. In the concomitant ancillary pharmacogenetic study, the primary endpoint was the association of polymorphisms with grade 3–4 CTCAE toxicity events (grade 2–4 for neurotoxicity). In 517 analyzed patients, grade ≥ 3 neutropenia and grade ≥ 2 neurotoxicity events occurred in 150 (29%) and in 132 patients (24.8%), respectively. Diarrhea grade ≥ 3 events occurred in 34 (6.5%) patients. None of the studied polymorphisms showed clinically relevant association with toxicity. Hopefully, genome-wide association studies will identify new and more promising genetic variants to be tested in future studies.
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