Functional treatment of bilateral posterior crossbite improves mandibular kinematics during chewing.

OBJECTIVES: To evaluate the effects of treatment of bilateral posterior crossbite (BPXB) on mandibular kinematics by the percentage of reverse chewing cycles (RCCs) during soft and hard bolus chewing before and after the correction of the malocclusion with function-generating bite (FGB). MATERIALS AND METHODS: This prospective study included 71 subjects: 19 patients with occlusally symmetric BPXB (M = 9; F = 10; mean age 9.3 ± 2.2[yr.mo]), 32 patients with occlusally asymmetric BPXB (19 with more teeth in crossbite on the right side (right prevalent side), M = 7; F = 12; mean age 8.2 ± 1.6 [yr.mo] and 13 on the left side, M = 7; F = 6; mean age 9.6 ± 1.9 [yr.mo]) and 20 controls without malocclusion (M = 8; F = 12; mean age 10.2 ± 1.7 [yr.mo]). Masticatory patterns were recorded before (T0) and after (T1) the correction of the malocclusion with FGB, with the K7-I® kinesiograph using standardized soft and hard boluses. RESULTS: BPXB was corrected in all included patients. At T0, the percentage of RCCs in BPXB was significantly increased compared to controls (P < .0001); symmetric BPXB showed no difference in RCCs between the sides, whereas asymmetric BPXB showed significantly more RCCs on the side with more teeth in crossbite (prevalent side). After treatment with FGB (T1), the percentage of RCCs was significantly reduced in both symmetric BPXB patients (soft bolus, P = .003; hard bolus, P < .001) and asymmetric BPXB patients (prevalent side: soft and hard bolus, P < .00001; non-prevalent side: soft bolus, P = .01 and hard bolus, P = .0002). CONCLUSION: Functional correction of BPXB with FGB significantly improved mandibular kinematics during chewing.

Improvement in the transverse dimension of dental arches in mixed dentition patients with posterior crossbite treated with functional therapy.

OBJECTIVES: To evaluate the effects of treatment of posterior crossbite (PXB) in the mixed dentition with the Function Generating Bite (FGB) appliance on the transverse dimension of the dental arches. MATERIALS AND METHODS: This study included 84 PXB patients (female = 46; male = 38; mean age, 8.2 ± 1.8 years) and 69 control (C) patients (female = 31; male = 38; mean age, 8.9 ± 1.4 years). Measurements were taken with digital calipers on maxillary and mandibular study casts before (T0) and after (T1) treatment for the following measures: intermolar (IMD), intermolar gingival (IMGD), intercanine (ICD), and intercanine gingival distances (ICGD). RESULTS: At T0, there was a significant difference in all maxillary measurements between the PXB and C groups (P < .001), reflecting maxillary hypoplasia in PXB patients. At T1, there was no difference between the groups. In PXB patients, the mean increase between T0 and T1 for IMD was 4.34 ± 2.42 mm; this difference measured 3.51 ± 2.19 mm for IMGD, 2.78 ± 2.37 mm for ICS, and 1.89 ± 1.7 mm for ICGD. There was no significant difference in mandibular measurements between groups at T0 and T1. CONCLUSIONS: Functional therapy with FGB is effective in significantly increasing the transverse dimension of the maxillary dental arch in PXB patients. Considering its efficacy in treating masticatory dysfunction, FGB may be considered a good treatment option for the correction of PXB in growing children.

Chewing Patterns and Muscular Activation in Deep Bite Malocclusion.

BACKGROUND: Deep bite, a frequent malocclusion with a high relapse rate, is associated with craniofacial features that need to be considered in the course of orthodontic treatment. METHODS: This study included 81 patients with deep bite malocclusion (11.4 ± 1.1 [yr.mo]; M = 32 and F = 49), and 14 age- and gender-matched controls (9.11 ± 1 [yr.mo]; M = 5 and F = 9). The patients with deep bite malocclusion were treated with functional therapy. The chewing cycles and masticatory muscle EMG activity were recorded concomitantly before treatment in both groups (n = 95). Following correction of the malocclusion, a second recording took place (n = 25). RESULTS: The kinematic variables showed the same dependency on bolus hardness in those with deep bite and in the controls. The masticatory muscle EMG activity was increased in those with deep bite, but decreased as a result of functional treatment. The chewing patterns showed a tendency towards a reduced lateral component, which significantly increased after treatment, indicating that functional therapy impacts the neuromuscular coordination of mastication, as well as dental positioning. CONCLUSIONS: Deep bite is a complex malocclusion, involving alterations in chewing and masticatory muscle activity. Orthognathodontic treatment should not only consider and correct the teeth position, but should also address muscular hyperactivity.

Assessment of Resistance Mechanisms and Clinical Implications in Patients with KRAS Mutated-Metastatic Breast Cancer and Resistance to CDK4/6 Inhibitors.

Despite therapeutic improvements, resistance to palbociclib is a growing clinical challenge which is poorly understood. This study was conducted in order to understand the molecular mechanisms of resistance to palbociclib, and to identify biomarkers to predict who will take advantage from cyclin-dependent kinase 4/6 inhibitors (CDK4/6i). A total of about a thousand blood samples were collected from 106 patients with hormone receptor positive (HR+) human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancer who received palbociclib in combination with fulvestrant as the first-line metastatic therapy enrolled in this study. The genotyping of their plasma cell-free DNA was studied, including serial plasma samples. Collectively, our findings identify the appearance of KRAS mutations leading to palbociclib resistance acquisition within 6 months, and provide critical information for the prediction of therapeutic responses in metastatic breast cancer. By monitoring KRAS status through liquid biopsy, we could predict who will take advantage from the combination of palbociclib and fulvestrant, offering highly-individualized treatment plans, thus ensuring the best patient quality of life.

Evaluation of masticatory function in patients with cleft lip and/or palate.

The aim of this study was to evaluate the masticatory pattern in children with cleft lip and/or palate (CL/P) through investigation of the prevalence of reverse sequencing chewing cycles. The study group included 18 patients with CL/P (mean age: 7.4 yr, SD: 1.4 yr), 15 of whom had dental crossbite. The controls included a group of 18 non-CL/P children with the same types of crossbite as the study group (mean age: 7.2 yr, SD: 1.5 yr) and a group of 18 non-CL/P subjects with normal occlusion (mean age: 9.8 yr, SD: 1.9 yr). Mandibular movements during chewing of soft and hard bolus were recorded with a kinesiograph. Kinematic signals were analysed using a custom-made software. A statistical analysis was performed to compare the degree of reverse-sequencing chewing cycles between patients and controls (Kruskal-Wallis test with Dwass-Steel-Critchlow-Fligner pairwise comparisons post hoc test). A significant difference between patients with CL/P and non-CL/P subjects with normal occlusion was highlighted on the left side of mastication, which was the side with the higher prevalence of crossbite with both types of bolus. No statistical differences were found between CL/P patients and healthy controls with crossbite. Cleft-affected patients with posterior crossbite exhibited an anomalous masticatory pattern with increased reverse chewing cycles on the crossbite side.

Gemcitabine-induced dilated-cardiomyopathy in patient with platinum-refractory ovarian-cancer: A case report and literature review.

INTRODUCTION: Gemcitabine is a nucleoside analog and pyrimidine antimetabolite that inhibits RNA synthesis, currently approved for use to treat a variety of cancers, among which ovarian cancers. Gemcitabine is considered relatively safe and it is generally well tolerated, with rarely reported cardiac side effects. CASE REPORT: We report a case of gemcitabine induced dilated cardiomyopathy in a 41-year-old woman receiving gemcitabine as second line treatment for platinum-resistant ovarian cancer without pre-existing hypertension or significant cardiac history.Management and Outcome: The patient presented with clinical symptoms and laboratory and imaging results suggestive of congestive cardiac failure, with a left ventricular ejection fraction of 15%. Gemcitabine administration was stopped and Furosemide with ACE-inhibitors and Beta-blocker agents were initiated. At that point the clinical situation improved: symptoms and findings disappeared with gemcitabine cessation. DISCUSSION: Our case demonstrated for the first time objective evidence for dilated cardiomyopathy induced by gemcitabine in a young patient with platinum-resistant ovarian cancer without pre-existing significant cardiac history. Although rare, gemcitabine-induced cardiotoxicity should be promptly recognized in order to take appropriate measures to manage it.

PD-L1 Expression on Circulating Tumour Cells May Be Predictive of Response to Regorafenib in Patients Diagnosed with Chemorefractory Metastatic Colorectal Cancer.

Regorafenib, targeting a broad range of receptor tyrosine kinases (RTKs), is an oral multikinase inhibitor which improves the progression-free survival (PFS) and overall survival (OS) of patients diagnosed with chemorefractory metastatic colorectal cancer (mCRC), making an immunosuppressive tumour microenvironment. The correlation between PD-1/PD-L1 expression and RTKs inhibition has been studied in several tumour types but has not been analyzed extensively in mCRC in the era of regorafenib. In this study, using liquid biopsy, we evaluated the opportunity to reveal if PD-L1 expression on circulating tumour cells (CTCs) could serve as a predictive biomarker of response and clinical benefit in patients treated with regorafenib as the third line of treatment. We analyzed a cohort of forty chemorefractory metastatic colorectal cancer patients, of whom twenty-six KRAS mutated, treated with regorafenib, all as the third line of treatment. Blood samples were collected from patients prior to treatment and longitudinally four and eight weeks after initiation of therapy. CTCs were identified using multiparametric flow cytometry; therefore, PD-L1 expression was evaluated. Objective responses were defined following the RECIST criteria v.1.1. Moreover, focusing on peripheral blood biomarkers, we found that high platelet-to-lymphocyte ratio (PLR) was an independent prognostic indicator of poor OS. For the first time, our study showed the usefulness of sequential assessments of CTCs as a non-invasive real-time biopsy to evaluate PD-L1 expression in patients diagnosed with mCRC and treated with regorafenib. Our analysis suggests that by assessing PD-L1 expression on CTCs, we could predict who will benefit from regorafenib, offering highly individualized treatment plans.

Individual and combined impact of lifestyle factors on atrial fibrillation in apparently healthy men and women: The EPIC-Norfolk prospective population study.

Background Lifestyle factors are important targets for prevention. The cumulative impact of healthy lifestyle on atrial fibrillation in the population has not been quantified. Design Prospective population-based cohort study. Methods Four lifestyle factors (normal weight, currently not smoking, no or moderate alcohol intake, and physically not inactive) were assessed in apparently healthy 21,499 men and women aged 39-79 years participating in the EPIC study in Norfolk, UK. The age and sex-adjusted hazard (95% confidence interval) of hospital admission with a diagnosis of atrial fibrillation during an average follow-up of 17.1 years was examined for each factor separately and for a health score comprising factors with significant impact. Results Normal weight, currently not smoking and low alcohol intake were associated with a significantly lower risk of atrial fibrillation, whereas not being physically inactive showed no significant association. We used a score of one point each for not smoking, low alcohol intake and body mass index 25 to 27.5 kg/m2, and two points for body mass index < 25 kg/m2. Compared with men and women with four health points, hazard ratios of atrial fibrillation were 1.25 (1.11-1.41), 1.56 (1.39-1.75), 1.83 (1.56-2.16) and 2.82 (1.85-4.29) for participants with three, two, one and no health points, respectively ( p < 0.0001 for trend). Results were consistent by sex, age, education level, social class and after excluding participants with hypertension and diabetes. Conclusion Three lifestyle factors combined predict an almost 2.8-fold difference in the risk of atrial fibrillation in men and women.