Assessment of bone quality using buccal and palatal autogenous cortical shells harvested from two different mandibular donor sites for maxillary alveolar ridge augmentation: a histomorphometric randomized clinical trial

Oral and Maxillofacial Surgery - This study aims to compare the quality of free autogenous bone grafts harvested from two different mandibular donor sites, used as onlay shells to augment...     

Reference values for fasting serum concentrations of thyroid-stimulating hormone and thyroid hormones in healthy Danish/North-European white children and adolescents

Thyroid-stimulating hormone (TSH) and thyroid hormones influence the functions of many organ systems, as well as child development and growth. Several studies have reported an association between ethnicity and thyroid hormones.

This study aims to explore pediatric serum concentrations of TSH, free triiodothyronine (fT3), and free thyroxine (fT4) and their relation to age and sex and subsequently to present pediatric reference intervals from healthy Danish/North-European white children.

A population-based cohort in Denmark of 2411 (1435 girls) healthy school children and adolescents aged 6.0–18.9?years were included. Fasting concentrations of serum TSH, fT3, and fT4 were determined from venous blood samples using immunologic chemiluminescent assays. Age- and sex-dependent percentiles were generated using the GAMLSS function.

Median values of fT3 and fT4, but not TSH, were lower in the older age group compared with the youngest age group for both sexes (all p?<?.05). A significant difference for fT3 was found between the sexes for all age groups (all p?<?.001). fT4 was negatively correlated with body mass index standard deviation scores in boys.

In conclusion, serum concentrations of thyroid hormones vary during childhood and adolescence and differ with age and sex.     

Optimized Hemodynamics by Implantation of a Dual Chamber Pacemaker After Heterotopic Cardiac Transplantation

A patient who underwent prior heterotopic cardiac transplantation had persistent complaints of dyspnea, palpitations, and fatigue in spite of normal pump function of the donor heart. Repeated Holter monitoring excluded paroxysmal arrhythmias. It was thought that synchronization of both heart rates might alleviate his symptoms. The intrinsic heart rate of the donor heart was 90 beats/min, the recipient heart was 60 beats/min with acceleration up to 130 beats/min on exercise. A DDD pacemaker was implanted, the atrial lead was positioned in the right ventricule of the donor heart and the ventricular lead in the atrium of the recipient heart. Search for an optimal AV interval was evaluated by echo-Doppler and intraarterial pressure recordings. By increasing the AV interval from 125 to 300 msec, the maximum aortic flow velocity of the recipient heart increased from 1.0 to 1.2 m/sec. Left ventricular end-diastolic diameter remained unchanged, left ventricular end-systolic diameter decreased from 52 to 48 mm. Wall motion of the recipient left ventricle improved. At an AV interval of 125 msec there was alternate systolic contraction of both hearts, resulting in arterial pressure waves at a rate of 180/min. This did not relieve his symptoms and he complained further of headaches. At an AV interval of 300 msec contraction of the recipient heart just preceded that of the donor heart, resulting in arterial pressure waves at a rate of 90/min, normalization of the wave form, relief of symptoms, and improvement of exercise tolerance.     

Proliferating cell nuclear antigen and Ki67 immunoreactivity in ameloblastomas

OBJECTIVE: This study used proliferating cell nuclear antigen (PCNA) and Ki67 to evaluate and compare the in situ proliferative activity of (1) solid and multicystic and (2) unicystic ameloblastomas in an attempt to provide a scientific basis for any differences in biologic behavior that exists between these 2 groups of lesions. STUDY DESIGN: Twenty archival tissue sections, 10 of primary unicystic and 10 of solid and multicystic ameloblastomas, were immunohistochemically stained with PCNA and Ki67 antisera. Immunoreactivity was evaluated by the counting of cells, and the data obtained were statistically analyzed. RESULTS: The results showed that cellular proliferative activity varied within the ameloblastoma types. The unicystic ameloblastomas showed statistically significantly higher PCNA and Ki67 labeling indices than the solid and multicystic variant. CONCLUSION: There appears, therefore, to be no correlation between proliferative activity as shown by these proteins and reported biologic behavior.     

High-resolution and quantitative spatial analysis reveal intra-ductal phenotypic and functional diversification in pancreatic cancer

A ‘classical’ and a ‘basal-like’ subtype of pancreatic cancer have been reported, with differential expression of GATA6 and different dosages of mutant KRAS. We established in situ detection of KRAS point mutations and mRNA panels for the consensus subtypes aiming to project these findings to paraffin-embedded clinical tumour samples for spatial quantitative analysis. We unveiled that, next to inter-patient and intra-patient inter-ductal heterogeneity, intraductal spatial phenotypes exist with anti-correlating expression levels of GATA6 and KRAS^G12D. The basal-like mRNA panel better captured the basal-like cell states than widely used protein markers. The panels corroborated the co-existence of the classical and basal-like cell states in a single tumour duct with functional diversification, i.e. proliferation and epithelial-to-mesenchymal transition respectively. Mutant KRAS^G12D detection ascertained an epithelial origin of vimentin-positive cells in the tumour. Uneven spatial distribution of cancer-associated fibroblasts could recreate similar intra-organoid diversification. This extensive heterogeneity with functional cooperation of plastic tumour cells poses extra challenges to therapeutic approaches. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.     

Overall survival and clinical characteristics of pancreatic cancer in BRCA mutation carriers

Background:

The BRCA1/2 proteins are involved in regulation of cellular proliferation by DNA damage repair via homologous recombination. Therefore, BRCA1/2 mutation carriers with pancreatic cancer may have distinct biologic outcomes.

Methods:

Patients with BRCA1/2-associated pancreatic ductal adenocarcinoma (PDAC) diagnosed between January 1994 and December 2012 were identified from databases at three participating institutions. Clinical data were collected. Disease-free survival and overall survival (OS) were analysed.

Results:

Overall, 71 patients with PDAC and BRCA1 (n=21), BRCA2 (n=49) or both (n=1) mutations were identified. Mean age at diagnosis was 60.3 years (range 33–83), 81.7% (n=58) had any family history of malignancy; 30% (n=21) underwent primary resection. Out of 71 participants, 12 received experimental therapy; one patient had missing data, these 13 cases were excluded from OS analysis. Median OS for 58 patients was 14 months (95% CI 10–23 months). Median OS for patients with stage 1/2 disease has not been reached with 52% still alive at 60 months. Median OS for stage 3/4 was 12 months (95% CI 6–15). Superior OS was observed for patients with stage 3/4 treated with platinum vs those treated with non-platinum chemotherapies (22 vs 9 months; P=0.039).

Conclusion:

Superior OS was observed for advanced-disease BRCA-associated PDAC with platinum exposure.     

High tumor interstitial fluid pressure identifies cervical cancer patients with improved survival from radiotherapy plus cisplatin versus radiotherapy alone

Radiotherapy (RT) with concurrent cisplatin (CRT) is standard treatment for locally advanced cervical cancer. However, not all patients benefit from the addition of cisplatin to RT alone. This study explored the value of pretreatment tumor interstitial fluid pressure (IFP) and hypoxia measurements as predictors of cisplatin response in 291 patients who were treated with RT (1994–1998) or RT plus concurrent cisplatin (1999–2009). Clinical characteristics were similar between the two groups, apart from a greater proportion of patients with pelvic lymph node metastases and hypoxic tumors in the CRT cohort. Patients were followed for a median duration of 5.6 years. Information about recurrence and survival was recorded prospectively. The addition of cisplatin to RT improved survival compared to treatment with RT alone (HR 0.61, p = 0.0097). This improvement was confined to patients with high‐IFP tumors at diagnosis (HR 0.40, p = 0.00091). There was no benefit of adding cisplatin in those with low‐IFP tumors (HR 1.05, p = 0.87). There was no difference in the effectiveness of cisplatin in patients with more or less hypoxic tumors. In conclusion, patients with locally advanced cervical cancer and high tumor IFP at diagnosis have greater benefit from the addition of cisplatin to RT than those with low IFP. This may reflect high tumor cell proliferation, which is known to influence IFP, local tumor control and patient survival.     

Bayesian estimation of six different sets of carbamazepine pharmacokinetic parameters in Egyptian adult epileptic patients.

The individualization of carbamazepine (CBZ) dosage regimen based on estimation of pharmacokinetic (PK) parameters and measurement of serum drug concentration in epileptic patients can help to control epilepsy. In a retrospective study, the predictive performance of six different sets of CBZ PK parameters selected according to the literature was evaluated in 60 adult epileptic patients. Patients were administered controlled release CBZ (dose range: 200-1200 mg day(-1)) as monotherapy and one steady state serum concentration of the drug was available for each patient. The Bayesian Program of Abbott (PKS system; Abbott Laboratories, Wiesbaden, Germany) was used in the prediction process. Predictive measures included estimation of mean prediction error (mpe) for bias, mean squared prediction error (mspe) and root mean squared prediction error (rmspe) for precision. The analysis showed that three of the investigated six sets achieved the best predictive performance in Egyptian patients and consequently, the PK parameters of any of these three sets can be used by the Bayesian approach as prior information for CBZ dose optimization among the Egyptian adult population.     

Rare mass of the anterior mediastinum: Thymolipomas

Thymolipoma is a rare benign neoplasm of the thymus containing both mature adipose tissue and thymic tissue. We report a case of a 34‐year‐οld man, presenting a mass of the anterior mediastinum, the radiology investigation and operatory piece diagnosed a thymolipoma.This study highlights the clinical diagnostic and therapeutic features as well as the evolutionary characteristics of this entity.     

PET/CT in initial staging and therapy response assessment of early mediastinal lymphoma

Objective

To detect accuracy of PET/CT in the initial staging, response after the first line and end of treatment in early mediastinal lymphoma patients compared to contrast CT.

Materials and methods

We studied 50 patients with pathologically proven lymphoma with a mean age = 27.5. All patients were at early stage. All patients performed CT and PET/CT for initial staging, after the first course of chemotherapy (after 4–6 weeks) and at the end of treatment (after 2–4 months).

Results

PET/CT upstaged 5 cases. At first line of treatment, PET/CT and CECT were agreeable in 32% of cases. PET/CT showed 100% sensitivity, 96.7% specificity, 95% positive predictive value and 100% negative predictive value. At the end of treatment both methods showed a 46% agreement. PET/CT was statistically significant in the follow up of hilar and axillary lymph nodes. PET/CT showed 100% sensitivity and specificity; compared to 62.5% sensitivity and 97.6% specificity for CECT in detection of extra-nodal disease sites.

Conclusion

PET/CT proved higher sensitivity and specificity over CECT. The major strength of PET/CT over CECT was its higher ability for detection of extra-nodal sites of lymphoma and excluding active disease in residual nodal mass lesions on follow up.