Different structural components of conventional papillary thyroid carcinoma display mostly identical BRAF status

Activating BRAF(T1799A) mutation is closely associated with a papillary thyroid carcinoma (PTC) histotype. The transversion is frequently detected in the conventional type, Warthin-like and tall cell variants, but is rare in the follicular variant of PTC. Conventional PTC is often presented with tumors of mixed architecture, which besides the papillary structures also contain areas with follicular and solid morphology in which the details of BRAF mutational status are unknown. We set out to differentially investigate the presence of mutated BRAF in the individual structural components microdissected from 44 formalin-fixed, paraffin-embedded PTC tissues from 40 patients. The mutation was detected in at least 1 structural component in 23 tumors (52%). Different structural components of the same tumor had identical BRAF status in 41/44 tumors (93%). In 3 tumors the BRAF(T1799A) mutation was found only in the papillary, but not in the follicular component. Mutational patterns identical to those in the primary tumors were found in 11/12 lymph node metastases (92%, including both BRAF(T1799A)-positive and -negative cases). The high concordance of the BRAF mutational status in structurally distinct areas suggests a rather homogeneous distribution of neoplastic epithelial cells in a conventional PTC tumor in most cases. These results imply the reliability of preoperative molecular diagnosis of PTC regardless of the type of tumor component at the site of biopsy sampling and suggest that the majority of patients with BRAF mutation-positive PTC may benefit from the targeted pharmacotherapy.     

Surgery in patients with haemophilia and high responding inhibitors: Izmir experience

Summary. This report evaluates the haemostatic efficacy of recombinant factor VIIa (rFVIIa) and activated prothrombin complex concentrate (APCC) in patients with haemophilia and high responding inhibitors who underwent major and minor surgery. Data pertaining to surgeries from 2001 to 2009 at a single centre were retrospectively analysed. During this period, 53 surgical procedures were performed in 30 haemophiliacs with high responding inhibitors. Mean age was 16.2 ± 9.4 years. Eleven major surgeries in 4 patients, 41 radioisotope synovectomies (RS) and one circumcision classified as minor surgery in 28 patients were performed. Among the major surgery procedures, four were treated with rFVIIa, five with APCC and two with sequential use of APCC and rFVIIa. We used rFVIIa at the dosage of 80–120 μg kg^?1 every 2 h and APCC 100 IU kg^?1 every 12 h for the major surgery. When performing RS, we used rFVIIa in 18 patients with 26 target joints and APCC in 9 patients with 15 target joints. Three consecutive doses of rFVIIa (90 μg kg^?1) were used at 2‐h intervals followed by additional three doses at 6‐h intervals. The initial dose of APCC was 75 IU kg^?1 followed by a second and third dose of 50 IU kg^?1 at 12‐h intervals. APCC and rFVIIa demonstrated excellent efficacy in our major and minor surgical interventions [100% (22/22) and 94% (31/33), respectively]. We had only two bleeding complications with rFVIIa. There were no thromboembolic complications. APCC and rFVIIa provide an effective and safe first line haemostatic therapy for inhibitor‐positive haemophiliacs, allowing both major and minor surgery to be successfully performed.     

Patient resources in the therapeutic education of haemophiliacs in France: their skills and roles as defined by consensus of a working group

Summary. The activities of ‘expert patients’ or ‘patient tutors’, who help educate their peers, are gaining recognition in the health care system. This study investigates the role played by such patients in therapeutic education programmes organized by caregivers to validate the role of patients in implementing the therapeutic education of haemophilic patients and to define the skills required for such activities. This study employs the consensus methodology recommended by France’s National Authority for Health. The working group includes seven caregivers from Hemophiliac Treatment Centers (HTCs) and three patients from the French Association of Hemophiliacs (FAH). The role of patients in haemophilia education is recognized. Patients participating in the education of their peers are referred to as ‘patient resources’. A patient resource should be an adult, a volunteer and live in the same region as his peers. Candidates are chosen by the FAH and the HTCs to serve based on their motivation to facilitate the education of other patients as well as on their psychological and pedagogical aptitudes. A patient resource participates in the conception and administration of therapeutic education programmes. He also mediates between the caregivers and the patients. He ensures that the patients understand the material and are able to apply their knowledge in daily life. His activities are governed by professional ethics. Seven categories of skills were defined, permitting the group to determine precisely which skills are required to function as a patient resource. Supervision of the patients is planned to reinforce reflexive practices in the patients. Evolution of the health care system has led patients to become involved in therapeutic education. This phenomenon calls for a framework to be developed and an evaluation of its eventual effects.     

BRAF mutations are associated with some histological types of papillary thyroid carcinoma

Mutations in the BRAF gene have recently been detected in a wide range of neoplastic lesions with a particularly high prevalence in melanoma and papillary thyroid carcinoma (PTC). The hot-spot mutation BRAF(V599E) is frequently detected in PTC (36-69%), in contrast to its absence in other benign or malignant thyroid lesions. In order to unravel whether there is any association between the occurrence of the BRAF mutation and the histological pattern of PTC, in this study a previous series of 50 PTCs was extended to 134 cases, including ten cases of PTC-related entities-hyalinizing trabecular tumour (HTT) and mucoepidermoid carcinoma (MEC). Using PCR/SSCP and sequencing, the BRAF(V599E) mutation was detected in 45 of the 124 PTCs (36%). No mutations were detected in any case of HTT and MEC. BRAF(V599E) was present in 75% of Warthin-like PTCs and 53% of conventional PTCs, whereas no BRAF(V599E) mutations were detected in any of the 32 cases of the follicular variant of PTC. BRAF(V599E) was also detected in 6 of 11 cases of the oncocytic variant of PTC that displayed a papillary or mixed follicular-papillary growth pattern and in none of the four oncocytic PTCs with a follicular growth pattern. A distinct mutation in BRAF (codon K600E) was detected in three cases of the follicular variant of PTC. This study has confirmed the high prevalence of BRAF(V599E) in PTC and has shown that the mutation is almost exclusively seen in PTC with a papillary or mixed follicular-papillary growth pattern, regardless of the cytological features of the neoplastic cells. The results support the existence of an oncocytic variant of PTC that should be separated from the oncocytic variant of follicular carcinoma and suggest that the follicular variant of PTC may be genetically different from conventional PTC.     

Type and prevalence of BRAF mutations are closely associated with papillary thyroid carcinoma histotype and patients’ age but not with tumour aggressiveness

A high prevalence of the BRAF^V600E somatic mutation was recently reported in several series of papillary thyroid carcinomas (PTC). This mutation appears to be particularly prevalent in PTC with a predominantly papillary architecture. Another BRAF mutation (K601E) was detected in a follicular adenoma and in some cases of the follicular variant of PTC. The few studies on record provided controversial data on the relationship between the occurrence of BRAF mutations and clinicopathologic parameters such as gender, age and tumour staging. In an attempt to clarify such controversies we decided to enlarge our previous series to 315 tumours or tumour-like lesions diagnosed in 280 patients, including a thorough analysis of several clinicopathologic features. The BRAF^V600E mutation was exclusively detected in PTC with a papillary or mixed follicular/papillary architecture both of the conventional type (46%) and of other histotypes, such as microcarcinoma (43%), Warthin-like PTC (75%) and oncocytic variant of PTC (55%). The BRAF^K601E mutation was detected in four of the 54 cases of the follicular variant of PTC (7%). The mean age of patients with conventional PTC harbouring BRAF^V600E (46.7 years) was significantly higher (P<0.0001) than that of patients with conventional PTC without BRAF^V600E (29.5 years). The BRAF (BRAF^V600E) mutated PTC did not exhibit signs of higher aggressiveness (size, vascular invasion, extra-thyroid extension and nodal metastasis) and were in fact less often multicentric than PTC without the mutation.V. Trovisco and P. Soares contributed equally to this workFundação para a Ciência e Tecnologia POCTI/FEDER (POCTI/NSE/48171/2002)     

Post-COVID syndrome: pulmonary complications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people worlwide and caused a pandemic that is still ongoing. The virus can cause a disease named as COVID-19, which is composed of multi systemic manifestations with a pulmonary system predominance. As the time passes, we are dealing more and more with a wide variety of effects and complications of the disease in survivors as far as with concerns about the clinical outcome and the timeline of symptoms in different patients. Since the lungs are the most involved organs and the post-COVID prolonged and persistent effects are mainly related to the pulmonary system, it is crucial to define and predict the outcome and to determine the individuals that can progress to fibrosis and loss of function of lungs. This review summarizes the current literature regarding the pulmonary complications in post-COVID syndrome and the management of these conditions.     

Measurement of family impact of skin disease: further validation of the Family Dermatology Life Quality Index (FDLQI)

Aim To adapt the Impact on Family scale (IOF), originally developed for families of children with chronic illnesses, for use in families of adult patients and to examine the convergent validity of the Family Dermatology Life Quality Index (FDLQI) by comparing it with the adapted version of the IOF scale. Methods Adult family members of patients with different skin diseases attending the out‐patients clinic of a secondary referral centre completed the FDLQI and the adapted version of the IOF scale, whereas patients completed the Dermatology Life Quality Index (DLQI). Results A total of 50 patients and 50 family members/partners participated in the study. The mean scores for the three instruments were as follows: FDLQI = 6.0 (SD = 6.4, median = 4); IOF scale = 27.9 (SD = 8.2, median = 29); DLQI = 5.4 (SD = 5.6, median = 3). There was no difference between male and female participants in the mean scores of any of the three instruments. The FDLQI demonstrated high internal consistency (Cronbach's α = 0.91). Factor analysis revealed the presence of one factor structure underlying the items of the FDLQI, which explained 55.8% of the total variance. The IOF scale also showed a high internal consistency (Cronbach's α = 0.89). The results of factor analysis revealed one dominant factor and three weaker factors, which together explained 72% of the total variance. The convergent validity of the FDLQI was demonstrated by a highly significant positive correlation between the mean FDLQI and the IOF scale scores (r_s = 0.61, P < 0.0001). All the items of the FDLQI also had significant correlations with the mean total IOF scale scores (P < 0.05). Conclusions The results of this study have demonstrated that with minor modifications IOF scale, which was originally developed for families of children suffering from chronic illnesses, can also be used in families of adult dermatology patients. The study has also provided further evidence of the validity of the newly developed FDLQI.