Tag: nevin manimala

J Clin Oncol. 2023 Nov 22:JCO2300825. doi: 10.1200/JCO.23.00825. Online ahead of print.

ABSTRACT

PURPOSE: CALGB (Alliance)/SWOG 80405 was a randomized phase III trial that in first-line patients with metastatic colorectal cancer (mCRC) treated with bevacizumab or cetuximab with chemotherapy. We aimed to discover novel mutated genes associated with prognosis and differential response to therapy with the biologics.

METHODS: Primary tumor DNA from 548 patients was sequenced using FoundationOne. The effect of mutated genes and mutations on overall survival (OS) was tested adjusting for microsatellite instability status, BRAF V600E, all RAS mutations, arm, sex, and age.

RESULTS: The median number (lower-upper quartile) of mutated genes was 5 (3-7), 5 (3-6) in microsatellite stable and 12.5 (4.5-32) in microsatellite instability-high tumors. Mutated KRAS and APC were more frequent in Black (53% and 85%) than White (27% and 65%, respectively) patients while BRAF V600E was less frequent in Black (5%) than White (14%) patients. The median OS in patients with BRAF non-V600E (2.2% of patients) was 31.9 months (95% CI, 15.1 to not applicable [NA]) similar to that of BRAF wild-type (WT) patients (31.2 months [95% CI, 29.0 to 33.9]). Mutated LRP1B (10.7% of patients) was associated with improved OS compared with WT LRP1B (hazard ratio, 0.57 [95% CI, 0.40 to 0.80]). RNF43 (5.6% of patients) interacted with treatment arms as, in the cetuximab arm, patients with mutated RNF43 had a median OS of 11.5 (95% CI, 10.8 to NA) months compared with 30.1 (95% CI, 24.9 to 35.3) months in patients with WT RNF43, whereas in the bevacizumab arm, patients with mutated RNF43 had a median OS of 25.0 (95% CI, 14.2 to NA) months compared with 31.3 (95% CI, 29.0 to 34.3) months in patients with WT RNF43.

CONCLUSION: These results can provide new tools to predict patient outcome and improve therapeutic decisions and trial participation in patient minorities. The molecular alterations identified in this study may direct biomarker-driven studies.

PMID:37992266 | DOI:10.1200/JCO.23.00825

Med Oral Patol Oral Cir Bucal. 2023 Nov 22:26044. doi: 10.4317/medoral.26044. Online ahead of print.

ABSTRACT

BACKGROUND: The relationship between the impacted mandibular third molar (IMTM) and the external root resorption (ERR) of the mandibular second molar (MSM) was analysed with cone-beam computed tomography (CBCT). The risk factors affecting the ERR of the MSM were examined to provide a reference.

MATERIAL AND METHODS: A total of 327 patients (total: 578 teeth) admitted to the Affiliated Hospital of Yanbian University for IMTM extraction from January 2017 to December 2019 was chosen and divided according to gender and age. The correlation between the IMTM and ERR of MSM was analysed, including inclination angle, impaction direction and depth. The relationship of mandibular ascending ramus classification with ERR of MSM was also analysed. In addition, the correlation between the MTM impaction type and the severity of ERR was analysed.

RESULTS: The incidence of ERR of MSM in male patients was higher than in females (27.9% vs.17.6%, p = 0.018). The occurrence and the site of ERR showed statistical differences in the inclination angle [(≤20°, 3.6%) vs. (21°-40°, 27.1%) vs. (41°-60°, 27.6%) vs. (61°-80°, 25.6%) vs. (>80°, 31.7%), p <0.001], impaction direction [(Vertical, 1.1%) vs. (Mesial, 32.7%) vs. (Horizontal, 25.3%), p <0.001] and depth of MTM [(Low position, 38.6%) vs. (Median position, 32.0%) vs. (High position, 13.7%), p <0.001]. Also, there was a significant difference in the mandibular ascending ramus type [(Class I, 17.4%) vs. (Class II, 32.3%) vs. (Class III, 44.9%), p <0.001]. In addition, the severity of ERR showed statistical differences in the mesial (40.9%, p<0.05), lower impaction (54.5%, p<0.05) depth of MTM and type III of mandibular ascending ramus (63.6%, p<0.05).

CONCLUSIONS: The inclination angle, impaction direction, and depth of MTM were the influencing factors for the occurrence and site of ERR. Also, mandibular ascending ramus type was the impact fact. For MTM with mesioangular, lower impaction, and mandibular ascending ramus with type III, the ERR of the MSM was severer.

PMID:37992149 | DOI:10.4317/medoral.26044

Med Oral Patol Oral Cir Bucal. 2023 Nov 22:26056. doi: 10.4317/medoral.26056. Online ahead of print.

ABSTRACT

BACKGROUND: Surgical extraction of the lower third molar (LTM) may trigger neurosensory injury of the inferior alveolar nerve, making extraction a real challenge. This study set out to assess whether is it possible to predict neurosensory alterations from preoperative imaging.

MATERIAL AND METHODS: A total of 99 patients underwent 124 impacted lower third molar (ILTM) surgeries. Prior to surgery, panoramic and CBCT images were evaluated in an attempt to predict a neurosensory disturbance. Preoperative data (ILTM position, panoramic radiograph signs, inferior alveolar nerve (IAN) location and its contact with the ILTM roots) and intra/postoperative findings (extraction difficulty and sensitivity alterations) were recorded. Descriptive and bivariate data analysis was performed. Statistical comparison applied the chi-square test, Fisher test, and one-way ANOVA test. Statistical significance was established with a confidence interval (CI) of 95%.

RESULTS: In 4.03% of cases, patients experienced neurosensory alterations. Of 124 ILTM positions in panoramic radiographs, 76 cases were considered to exhibit a potential neurosensory risk as they presented two or more types of superimposed relationships between ILTM and mandibular canal. Of these, alterations were reported in only three cases (3.95%). Of the 48 remaining ILTM images presenting only one sign, neurosensory alterations were observed in two cases (4.17%). No permanent alterations were recorded in any of the five cases observed.

CONCLUSIONS: Within the limitations of the present study, prediction of neurosensory alterations prior to ILTM extraction by means of preoperative imaging did not show a significant statistical correlation with post-surgical incidence. Nevertheless, interruption of the canal´s white line (ICWL) or a diversion of the canal (DC) may predict an increased risk of IAN injury.

PMID:37992147 | DOI:10.4317/medoral.26056

Med Oral Patol Oral Cir Bucal. 2023 Nov 22:26094. doi: 10.4317/medoral.26094. Online ahead of print.

ABSTRACT

BACKGROUND: To evaluate bone regenerative capacity of cryoprotected corticocancellous allogeneic bone graft performed in type II and III post-extraction sockets for ridge preservation after twelve weeks in-vivo.

MATERIAL AND METHODS: Twenty-seven type II or III bony-walled extraction sockets (mandible and maxilla) were selected for this study. Following atraumatic tooth-extraction a cryoprotected corticocancellous allogeneic bone graft material and a resorbable porcine-derived collagen membrane were used for ridge preservation. During re-entry surgery at approximately 12 weeks, bone core biopsies were obtained using a 3.2 mm trephine drill and samples were histologically processed and subjected to qualitative and quantitative histomorphometric analysis. Quantitative data was analyzed using a general linear mixed model with results presented as mean values with the corresponding 95% confidence interval values.

RESULTS: Healing without incident and ridge preservation allowed for the placement of dental implants after 12 weeks in 25 out of the 27 treated socket sites. Analyses yielded an average of ~21.0±7% of old/native bone, ~17±5.5% of newly regenerated bone (total of ~38±12.8% for all bone), 0.23±0.14% of new bone presenting with nucleating sites within the matrix, ~52±5.12% of soft tissue, and 3.6±2.09% of damaged bone. The average regenerated bone was statistically analogous to that of old/native bone (p=0.355). Furthermore, an atypical histological pattern of bone regeneration was observed, with newly formed bone exhibiting “infiltration-like” behavior and with new bone nucleating sites observed within the demineralized bone matrix.

CONCLUSIONS: Cryoprotected corticocancellous allogeneic bone-graft demonstrated osteoconductive, osteoinductive, and osteogenic properties, yielding unique healing patterns which does warrant further investigation.

PMID:37992144 | DOI:10.4317/medoral.26094

Med Oral Patol Oral Cir Bucal. 2023 Nov 22:26237. doi: 10.4317/medoral.26237. Online ahead of print.

ABSTRACT

BACKGROUND: This study retrospectively analyzed the risk factors for oral mucositis (OM) during cetuximab treatment.

MATERIAL AND METHODS: We screened patients using cetuximab and retrospectively evaluated the presence of OM based on medical records. We collected information from 2 years of evaluations. Patient medical records were reviewed to obtain data on chemotherapy cycle and dose, sex, age, primary tumor, TNM stage, and head and neck radiotherapy (HNR) history. The X2 test and multinomial logistic regression were used for statistical analysis (SPSS 20.0, p < 0.05).

RESULTS: Among 1831 patients, OM was showed in 750 in any grade (41%), during cetuximab treatment. Most patients were female (n=944, 51.6%), <70years-old (n=1149, 62.8%), had larynx cancer (n=789, 43.1%) in T4 (n=579, 47.7%), N0 (n=509, 52.6%) stages. Primary tumor surgery was performed in 1476 (80.6%) patients, radiotherapy in 606 (33.1%) patients and cetuximab protocols most used involved up to four cycles (n=1072, 58.5%) of <400mg (n=996, 54.4%) cetuximab doses. Female (OR [odds ratio] = 2.17, CI95% = 1.26-3.75), >70 years-old patients (OR = 16.02, CI95% = 11.99-21.41), with HHNR (OR = 1.84, 1.41-2.40), treated with >4 cycles (OR = 1.52, CI95% = 1.16-2.01) and high doses of cetuximab (OR = 3.80, CI95% = 2.52-5.71) are the greatest risk factors for OM.

CONCLUSIONS: Since the clinical benefit of cetuximab in the treatment of older patients is limited and there is a high OM, especially in women with head and neck treated with radiotherapy, high doses and a high number of cetuximab cycles must be administered with caution.

PMID:37992137 | DOI:10.4317/medoral.26237

Med Oral Patol Oral Cir Bucal. 2023 Nov 22:26280. doi: 10.4317/medoral.26280. Online ahead of print.

ABSTRACT

BACKGROUND: Although it is known that the soft tissues around dental implants have an impact on its health and cause marginal bone loss, it is still uncertain exactly how. The aim of the study is to evaluate the effect of vertical mucosal thickness and keratinized mucosal width on marginal bone loss and periodontal clinical parameters in the 2-year follow-up of implants placed at the bone level.

MATERIAL AND METHODS: 87 bone-level dental implants were placed in 31 patients. The initial vertical mucosal thickness (VMT) was recorded at implant placement. At the second year follow-up, gingival index (GI), plaque index (PI), probing depth (PD), bleeding on probe (BOP), radiographic marginal bone loss (MBL) and width of the keratinized mucosa (KMW) were all measured. MBL and periodontal clinical parameters were evaluated separately according to VMT and KMW. VMT was categorized into two groups, Group 1 (≤ 2mm) and Group 2 (> 2 mm). KMW was divided into two groups, Group A (< 2mm) and Group B (≥ 2 mm).

RESULTS: Dental implants had a mean MBL of 0.39 ± 0.57 mm in the 2-year follow-up. MBL in Group 1 and 2 was 0.39 ± 0.42 mm and 0.38 ± 0.65 mm, respectively. MBL in Group A and B was 0.41 ± 0.68 mm and 0.37 ± 0.49 mm, respectively. No significant difference in MBL was found in the KMW and VMT groups (p>0.05). The group with the thicker vertical mucosa was shown to have statistically substantially higher PI and GI values (p=0.040 and p=0.014, respectively).

CONCLUSIONS: Within the limits of the present study, it was observed that the vertical mucosal thickness and the width of the keratinized mucosa did not affect the marginal bone loss. In addition, it was observed that the insufficiency of the width of the keratinized mucosa did not affect the periodontal clinical parameters, but the thicker vertical mucosa could increase the plaque index and gingival index.

PMID:37992136 | DOI:10.4317/medoral.26280

Mol Biol Evol. 2023 Nov 22:msad252. doi: 10.1093/molbev/msad252. Online ahead of print.

ABSTRACT

Hybridization is recognized as an important evolutionary force, but identifying and timing admixture events between divergent lineages remains a major aim of evolutionary biology. While this has traditionally been done using inferential tools on contemporary genomes, the latest advances in paleogenomics have provided a growing wealth of temporally distributed genomic data. Here, we used individual-based simulations to generate chromosome-level genomic data for a two-population system and described temporal neutral introgression patterns under a single- and two-pulse admixture model. We computed six summary statistics aiming to inform the timing and number of admixture pulses between interbreeding entities: lengths of introgressed sequences and their variance within-genomes, as well as genome-wide introgression proportions and related measures. The first two statistics could confidently be used to infer inter-lineage hybridization history, peaking at the beginning and shortly after an admixture pulse. Temporal variation in introgression proportions and related statistics provided more limited insights, particularly when considering their application to ancient genomes still scant in number. Lastly, we computed these statistics on Homo sapiens paleogenomes and successfully inferred the hybridization pulse from Neanderthal that occurred approximately 40 to 60 kya. The scarce number of genomes dating from this period prevented more precise inferences, but the accumulation of paleogenomic data opens promising perspectives as our approach only requires a limited number of ancient genomes.

PMID:37992125 | DOI:10.1093/molbev/msad252

Psychiatr Danub. 2023 Winter;35(4):563-571. doi: 10.24869/psyd.2023.563.

ABSTRACT

BACKGROUND: This study aims at investigating the mediating role of rumination and COVID-19 burnout in the relationship among depression, resilience and intolerance of uncertainty.

SUBJECTS AND METHODS: This is a correlational study. The study sample is composed of 436 (F=259, M=177) Turkish university students recruited via convenience sampling method. The participants responded to the Depression Scale, COVID-19 Burnout Scale, Rumination Scale, Resilience Scale and Intolerance of Uncertainty Scale face to face. The model that was developed within the scope of the current study was tested via path analysis, which is a technique of Structural Equation Modelling (SEM).

RESULTS: The study findings show that resilience and intolerance of uncertainty predict depression and rumination at a statistically significant level. Moreover, rumination directly predicts COVID-19 burnout, while COVID-19 burnout predicts depression. On the other hand, indirect effect modelling shows that resilience predicts depression with the mediating effect of rumination and COVID-19 burnout at a statistically significant level. Lastly, intolerance of uncertainty predicts depression with the mediating effect of rumination and COVID-19 burnout at a statistically significant level.

CONCLUSION: The current findings suggest that an increase in the level of intolerance of uncertainty and a decrease in the level of resilience increase rumination, which in turn increases depression by increasing COVID-19 burnout.

PMID:37992101 | DOI:10.24869/psyd.2023.563

Psychiatr Danub. 2023 Winter;35(4):535-543. doi: 10.24869/psyd.2023.535.

ABSTRACT

BACKGROUND: Non-attendance to outpatient mental health appointments is associated with adverse clinical and financial outcomes. The aim of this study was to investigate the rates of non-attendance to outpatient Consultation-Liaison Psychiatry (CLP) appointments and the factors associated with non-attendance.

SUBJECTS AND METHODS: Retrospective cohort study, including two groups of data: 950 initial and 3503 follow-up appointments between 01/01/2015 and 31/12/2019. We employed descriptive statistics, parametric/non-parametric tests and logistic regression analysis. We used a range of environmental, socio-demographic and service-related characteristics as independent parameters and non-attendance as the dependent parameter.

RESULTS: Initial and follow-up non-attendance rates were 27.5% and 18.8% respectively. Opting-out text message reminders was associated with both initial and follow-up non-attendance. Higher education was associated with initial non-attendance, whereas lower education with follow-up non-attendance. Other factors associated with non-attendance to initial appointments were: English being the participant’s primary communication language, having an appointment with a psychiatrist as opposed to a trained nurse or Cognitive Behavioural Therapist, and longer waiting time. Follow-up non-attendance was also associated with younger age, shorter driving distance and higher income/employment.

CONCLUSION: We suggest that improving opt-in rates through a combination of staff and patient education and promotion, improving waiting lists, reducing the stigma associated with seeing a psychiatrist, but also perhaps targeting different socio-economic groups of patients with different strategies should be the focus of policy making to tackle non-attendance. Further research into patient-related and environmental factors, such as day of the week, driving distance, language of primary communication, education, income and employment is warranted in order to design more effective policies and improve engagement with CLP, but also psychiatric services in general.

PMID:37992098 | DOI:10.24869/psyd.2023.535

Psychiatr Danub. 2023 Winter;35(4):523-534. doi: 10.24869/psyd.2023.523.

ABSTRACT

BACKGROUND: Misattribution of motivational salience to non-salient (neutral) stimuli could be viewed as a hallmark of psychosis in schizophrenia. Studies have recently revealed increased subjective experience of emotional arousal (EA) to neutral social stimuli in paranoid schizophrenia psychosis, suggesting a misattribution of emotional salience to them. We examined this phenomenon directly by quantifying the level of EA subjectively attributed to low-arousal, neutral-valenced faces.

SUBJECTS AND METHODS: Patients with remitted schizophrenia (PG) (n=26), first-degree relatives of schizophrenic patients (RG) (n=25), and healthy controls (HCG) (n=36) were compared in terms of oxidative stress parameters -serum Superoxide Dismutase, Catalase, Glutathione Peroxidase (GPx), Nitrite, Nitrate, Malondialdehyde, and Total Glutathione levels-, social cognition measured by the Reading the Mind in the Eyes Test and working memory measured by the N-back Task. Groups were compared, assuming that HCG had a genetically lower risk of schizophrenia compared to PG and RG.

RESULTS: HCG performed significantly better than PG and RG, who were genetically at high risk, in terms of social cognition (respectively p=0.000, p=0.014), working memory (respectively p=0.001, p=0.003), and had statistically lower Glutathione Peroxidase (GPX) level than the PG and RG (both p:0.000). After controlling for the effect of the general intellectual abilities measured by the Raven Standard Progressive Matrices Test and working memory the differences between groups on the Eyes Test disappeared (p=0.057). However, this value tended to be significant.

CONCLUSION: It was concluded that social cognition and working memory and GPx level may be used as endophenotypes and social cognition, working memory, and general intellectual skills are different but strongly related constructs. Endophenotypes guide treatment targets even after the disease has developed. The results of our study showed that in addition to psychopharmacological treatments, interventions to reduce oxidative stress and approaches to improve cognitive skills will have a positive impact on the disease’s progression.

PMID:37992097 | DOI:10.24869/psyd.2023.523