Efficacy and safety of SGLT2 inhibitors in individuals with type 1 diabetes under continuous subcutaneous insulin infusion: a real-world study.

Objective. Adjuvant therapy with sodium-glucose cotransport 2 inhibitors (SGLT2i) in type 1 diabetes (T1D) is associated with an improvement in glycemic control, but increases the risk of diabetic ketoacidosis (DKA). However, real-life studies in individuals with T1D under continuous subcutaneous insulin infusion (CSII) are still scarce. We present the first real-life study performed in patients with T1D exclusively treated with CSII. The aim of the present study was to assess the metabolic impact and safety of SGLT2i in T1D individuals under CSII. Methods. Retrospective study includes 34 T1D adult individuals under CSII, who started SGLT2i until 30th June 2021. Data regarding the glycemic control and acute diabetes complications at the moment of introduction of SGLT2i and after 3, 6, and 12 months of use were collected. Results. Twenty-three individuals were included. Comparing with the moment of SGLT2i introduction after 3, 6, and 12 months of use, there was a statistically significant increase of time in range (TIR) (∆T3M=12.8%; ∆T6M=11.5%; ∆T12M=11.1%), and a decrease in time above range (∆T3M=13.6%; ∆T6M=11.9%; ∆T12M=10.5%). There were no significant differences in time below the range. Mean glucose and mean glucose management indicator significantly reduced in the 3 evaluated moments. A significant reduction in median weight was also observed (∆T6M=2 kg; ∆T12M=4.5 kg). Two patients (8.7%) developed mild euglycemic DKA during SGLT2i treatment, both were women and had body mass index (BMI) <27 kg/m2. One of them had a total daily insulin dose (TDDI) reduction of 26.9% after 3 months of use. Conclusions. The use of SGLT2i, as an adjuvant treatment in T1D individuals under CSII, was associated with a significant increase of TIR without increasing time in hypoglycemia. It also had a weight benefit. Careful use in selected participants is necessary to reduce the occurrence of DKA.

Characteristics and treatment outcomes of micromegaly - acromegaly with apparently normal basal GH: A retrospective study and literature review.

Objective. Micromegaly describes a subgroup of patients with clinically evident acromegaly and elevated insulin-like growth factor I (IGF-I) with apparently normal basal growth hormone (bGH) and often a glucose-suppressed growth hormone (GH) of <1 ng/mL at diagnosis. It is controversial whether this condition is a distinct clinical entity or a classic acromegaly in early stages. The aim of the present article was to characterize the prevalence, clinical and biochemical characteristics, and therapeutic outcomes of micromegaly. Methods. A retrospective study of patients with an acromegaly followed ≥1 year at a tertiary center from 1995 to 2019. Patients without IGF-I or GH measurements at diagnosis were excluded. At diagnosis, bGH was considered normal if <2 ng/mL. Results. From 74 patients with acromegaly, 6 (8.1%) had normal bGH levels. There was no difference in the gender distribution, median diagnostic delay, and follow-up time between patients with normal bGH and elevated bGH. Patients with normal bGH were significantly older at time of the first acromegalic manifestation and diagnosis they had significantly lower nadir post-glucose GH and IGF-I levels, and tended to have a higher prevalence of obesity than patients with the elevated bGH. The frequency of acromegalic symptoms, signs, and other comorbidities than obesity was similar between groups. Five patients (83.3%) with normal bGH presented microadenomas. Post-operative remission and outcomes at last visit were comparable between patients with or without normal bGH. Conclusions. Normal bGH acromegaly is relatively uncommon in our patients. These patients showed differentiating characteristics from the classical acromegaly with elevated bGH. Further studies are needed to extend the knowledge about its clinical behavior, therapeutic outcomes, morbidity, and mortality.

Are we interconnected? A qualitative study on the role and perception of different actors on malaria social behaviour change interventions in rural Mozambique.

BACKGROUND: Interconnecting institutions (health and education sector) and community (through a network of community structures) in social and behaviour change (SBC) activities can add value in an effort for malaria prevention towards a long-term objective of elimination. This approach has been implemented since 2011 in some rural districts of Mozambique. The objective of this study is to describe the perceptions of community and institutional actors on malaria prevention interventions in rural Mozambique. METHODS: A descriptive qualitative study with a constructivist research paradigm was conducted in October 2018 in two rural districts of Zambezia Province with high malaria burden in Mozambique. Key-informant sampling was used to select the study participants from different actors and layers: malaria community volunteers, health professionals, non-governmental actors, and education professionals. In-depth interviews (IDIs) and focus group discussions (FGDs) were used to explore the perceptions of these actors. Classic content analysis looking for themes and semantics was used, and saturation guided the sample size recruitment. RESULTS: A total of 23 institutional actor IDIs took place, and 8 FGDs were held. Four themes emerged from the content analysis: (1) organizational and functional aspects; (2) knowledge about malaria; (3) perception of institutional actors on SBC and community involvement; and, (4) perception of institutional actors on the coordination and leadership on SBC malaria interventions. Community structures were well organized, linked to the health sector and operational, with good knowledge of malaria prevention. Education sector (school teachers) links with the health sector were in some cases good, and in other cases, non-existent. The importance of SBC interventions for malaria control was recognized by health actors, although the activities are delegated to non-governmental institutions. Domestic budgetary allocation constraints, quality of intervention and lack of SBC standard indicators were also identified by health actors as aspects for improvement. CONCLUSIONS: Community structures, volunteers and primary school teachers have good knowledge on malaria prevention and regularly sensitize community members and students. Institutional health actors and partners recognize their role on malaria prevention activities, however, more interconnection is needed at different levels.

Apolipoprotein B and non-high-density lipoprotein cholesterol reveal a high atherogenicity in individuals with type 2 diabetes and controlled low-density lipoprotein-cholesterol.

BACKGROUND: Lipid-lowering therapy is guided by Low-density-lipoprotein cholesterol (LDL-c) levels, although the cardiovascular disease (CVD) risk could be better reflected by other lipid parameters. This study aimed at comparing a comprehensive lipid profile between patients with type 2 diabetes mellitus (T2DM) with LDL-c concentration within and above target. METHODS: A comprehensive lipid profile was characterized in 96 T2DM patients. The European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) 2016 and 2019 Guidelines for the Management of Dyslipidemias were used to define LDL-c targets. RESULTS: In this population, only 28.1 and 16.7% of patients had mean LDL-c levels within target, as defined by the 2016 and 2019 guidelines, respectively. Applying the 2016 guidelines criteria, in patients with LDL-c within target, 22, 25 and 44% presented non-high-density lipoprotein cholesterol (non-HDL-c), Apolipoprotein B (ApoB) and oxidized LDL-c levels above the recommended range, respectively, whereas according to the 2019 guidelines criteria, 50, 39 and 44% of the patients with LDL-c within target had elevated high-density lipoprotein cholesterol (HDL-c), ApoB and oxidized LDL-c levels, respectively. LDL-c was strongly correlated with non-HDL-c (r = 0.850), ApoB (r = 0.656) and oxidized LDL-c (r = 0.508). Similarly, there was a strong correlation between non-HDL-c with both ApoB (r = 0.808) and oxidized LDL-c (r = 0.588). CONCLUSIONS: These findings emphasize the limitations of only considering LDL-c concentration for cardiovascular (CV) risk assessment. Targeting only LDL-c could result in missed opportunities for CV risk reduction in T2DM patients. These data suggest that non-HDL-c, ApoB and oxidized LDL-c levels could be considered as an important part of these patients' evaluation allowing for a more accurate estimation of CV risk and hopefully better management of these high-risk patients.

Comparison of Cytological Adequacy between 23- and 25-Gauge in Ultrasound-Guided Fine-Needle Aspiration of Thyroid Nodules: A Single-Center Prospective Study.

INTRODUCTION: Approximately 15% of fine-needle aspiration (FNA) of thyroid nodules are considered nondiagnostic. Several factors are potentially involved, including clinical and nodule features but also the gauge (G) of the needle used. However, few studies have compared the cytological adequacy obtained with different gauge needles and the data are controversial. We aimed to evaluate cytological adequacy results using 23- or 25-G needles. METHODS: This study is an observational and prospective study of thyroid nodules submitted to ultrasound-guided FNA. The procedure was performed randomly using 23- or 25-G needles. The samples were reported by different cytopathologists who were blinded to the information of the gauge of the needle used. Statistical analysis was performed to compare cytological adequacy of FNA between the two groups. RESULTS: A total of 177 thyroid nodules were included - 98 (55.4%) using 23-G and 79 (44.6%) using 25-G needles. The 23-G group presented a higher rate of cytological adequacy (69.4% [68/98] vs. 46.8% [37/79], p = 0.002). No differences were found between the two groups regarding patient or nodule characteristics. On logistic regression, 23-G needles correlated with better cytological adequacy (unadjusted OR 2.57 [95% CI: 1.39-4.77]), even after adjusting for nodule dimension, location, and type of cytology (slides +/- additional liquid-based cytology) (adjusted OR 2.44 [95% CI: 1.23-4.84]). CONCLUSION: The gauge of the needle used was found to be an independent predictor of cytological adequacy, with 23-G needles providing more adequate samples. Further investigation is needed to confirm our results in order to stablish the optimal diagnosis technique.

Evaluation of Usage of a Fracture Risk Assessment by FRAX Tool in Adults With Type 2 Diabetes Mellitus.

BACKGROUND: Fragility fractures are increasingly recognized as a complication of type 2 diabetes mellitus (T2DM). The FRAX-Port® is a calculation tool that assesses the 10-year risk of either major and hip fracture, integrating several clinical risk factors, including T2DM. We aimed to evaluate the fracture risk in adults with T2DM and determine the rate of patients at high risk for fracture under anti-osteoporotic therapy. METHODS: We developed a cross-sectional study, including a convenience sample of adults with T2DM, followed in our tertiary center between 2019 and 2022. Fracture risk was evaluated according to FRAX-Port®. RESULTS: One hundred adults were included, 54% male, with a mean age of 68.4±9.2 years. Respecting fracture risk factors, 17% had a previous fragility fracture, 12% had a history of hip fracture in their parents, 9% had active alcohol consumption, and 4% had active smoking. Additionally, 17% presented secondary osteoporosis, being the most frequent cause of systemic corticosteroid exposure (10%). Regarding diabetes-specific risk factors, 94% had a diabetes duration longer than five years; HbA1c greater than 7% in 70%; 42% had diabetic retinopathy, 33% had diabetic chronic kidney disease, 18% had peripheral neuropathy, and 7% had autonomic neuropathy; 83% were on insulin, 2% on canagliflozin and 1% on pioglitazone. According to the FRAX-Port®, the median probability of major fracture was 6.8% (IQR 6.9), and hip fracture was 2.4% (IQR 3.9). Fracture risk was high, intermediate, and low at 41%, 15%, and 44%, respectively. Lastly, 56% of participants should undergo bone densitometry and 45% had a formal recommendation to begin an anti-osteoporotic treatment. However, only 6% were under anti-osteoporotic therapy: bisphosphonates (5%) and denosumab (1%). CONCLUSIONS: More than a third of T2DM patients evaluated had a high fracture risk. We found that FRAX-Port® is an easy-to-apply tool, which helps in the decision to perform densitometry or to institute anti-osteoporotic therapy. Given the increasing prevalence of T2DM and the associated risk of falls, this study highlights the need to recognize the fracture risk in these patients, usually a forgotten complication during the screening of risk factors for adverse events in adults with T2DM.

COVID-19 in a Portuguese whole blood donor population.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), leading to pneumonia and acute respiratory distress syndrome. The COVID-19 pandemic had a major impact on the stock of blood banks worldwide. This study aims to assess the prevalence of COVID-19 in a population of whole blood donors and analyze the possible association between blood group and susceptibility to the disease and the impact of adopting preventive measures against SARS-CoV-2 infection. Material and methods: This retrospective study included all whole blood donors from a Portuguese hospital between July and September 2021. A self-assessment questionnaire was used to collect data on COVID-19 infection, vaccination, and preventive measures. Statistical analysis was performed using Chi-square and Mann-Whitney U tests. Results: The prevalence of COVID-19 in the donor population was 11.96% (n = 97), with only 2 cases of serious illness requiring hospitalization. No association was found between blood group and disease susceptibility. Older men were less likely to adopt preventive measures. The vaccination rate was high, with 84.26% of donors having received at least one dose of the vaccine. Seven donors declined COVID-19 vaccination. Preventive measures did not differ based on COVID-19 infection status or vaccination. Discussion: Although there was a higher frequency of COVID-19 in group A donors, the blood group was not associated with susceptibility to infection. The donor population consisted of young individuals without comorbidities, showing a COVID-19 prevalence like the general population and few severe cases. The high vaccination rate and adoption of preventive measures likely contributed to these findings.

Inappropriate gestational weight gain impact on maternofetal outcomes in gestational diabetes.

OBJECTIVE: To evaluate the association between the dimension of deviation from appropriate gestational weight gain (GWG) and adverse maternofetal outcomes in women with gestational diabetes mellitus (GDM). METHODS: We performed a multicentric retrospective study based on the Portuguese GDM Database. Women were classified as within GWG, insufficient (IGWG) or excessive (EGWG) than the Institute of Medicine recommendations. EGWG and IGWG were calculated for each prepregnancy BMI category. Large-for-gestational-age (LGA) and macrosomia were defined as a birthweight more than the 90th percentile for the gestational age and newborn weight greater than 4000 g, respectively. Logistic regression models (adjusted odds ratio [aOR] plus 95% confidence interval [95%CI]) were derived to evaluate the association between EGWG or IGWG and adverse maternofetal outcomes. RESULTS: A total of 18961 pregnant women were included: 39.7% with IGWG and 27.8% with EGWG. An EGWG over 3 kg was associated with a higher risk of LGA infants (aOR 1.95, 95%CI 1.17-3.26) and macrosomia (aOR 2.01, 95%CI 1.23-3.27) in prepregnancy normal weight women. An EGWG greater than 4 kg was associated with a higher risk of LGA infants (aOR 1.67, 95%CI 1.23-2.23) and macrosomia (aOR 1.90, 95%CI 1.38-2.61) in obese women. In overweight women, an EGWG above 3.5 kg was associated with a higher risk of LGA infants (aOR 1.65, 95%CI 1.16-2.34), macrosomia (aOR 1.85, 95%CI 1.30-2.64), preeclampsia (aOR 2.40, 95%CI 1.45-3.98) and pregnancy-induced hypertension (aOR 2.21, 95%CI 1.52-3.21). An IGWG below -3.1 kg or -3kg was associated with a higher risk of small-for-gestational-age [SGA] infants in women with normal (OR 1.40, 95%CI 1.03-1.90) and underweight (OR 2.29, 95%CI 1.09-4.80), respectively. CONCLUSIONS: Inappropriate gestational weight gain seems to be associated with an increased risk for adverse maternofetal outcomes, regardless of prepregnancy BMI. Beyond glycemic control, weight management in women with GDM must be a focus of special attention to prevent adverse pregnancy outcomes.KEY MESSAGESThe dimension of deviation from appropriate gestational weight gain was associated with an increased risk for adverse maternofetal outcomes among women with gestational diabetes.Weight management must be a focus of special attention in women with gestational diabetes to prevent adverse pregnancy outcomes.

In vitro and in vivo evaluation of electrospun poly (ε-caprolactone)/collagen scaffolds and Wharton's jelly mesenchymal stromal cells (hWJ-MSCs) constructs as potential alternative for skin tissue engineering.

Dermal substitutes bear a high clinical demand because of their ability to promote the healing process of cutaneous wounds by reducing the healing time the appearance and improving the functionality of the repaired tissue. Despite the increasing development of dermal substitutes, most of them are only composed of biological or biosynthetic matrices. This demonstrates the need for new developments focused on using scaffolds with cells (tissue construct) that promote the production of factors for biological signaling, wound coverage, and general support of the tissue repair process. Here, we fabricate by electrospinning two scaffolds: poly(ε-caprolactone) (PCL) as a control and poly(ε-caprolactone)/collagen type I (PCol) in a ratio lower collagen than previously reported, 19:1, respectively. Then, characterize their physicochemical and mechanical properties. As we bear in mind the creation of a biologically functional construct, we characterize and assess in vitro the implications of seeding human Wharton's jelly mesenchymal stromal cells (hWJ-MSCs) on both scaffolds. Finally, to determine the potential functionality of the constructs in vivo, their efficiency was evaluated in a porcine biomodel. Our findings demonstrated that collagen incorporation in the scaffolds produces fibers with similar diameters to those in the human native extracellular matrix, increases wettability, and enhances the presence of nitrogen on the scaffold surface, improving cell adhesion and proliferation. These synthetic scaffolds improved the secretion of factors by hWJ-MSCs involved in skin repair processes such as b-FGF and Angiopoietin I and induced its differentiation towards epithelial lineage, as shown by the increased expression of Involucrin and JUP. In vivo experiments confirmed that lesions treated with the PCol/hWJ-MSCs constructs might reproduce a morphological organization that seems relatively equivalent to normal skin. These results suggest that the PCol/hWJ-MSCs construct is a promising alternative for skin lesions repair in the clinic.

Maturity-onset diabetes of the young in a large Portuguese cohort.

AIMS: Monogenic forms of diabetes that develop with autosomal dominant inheritance are classically aggregated in the Maturity-Onset Diabetes of the Young (MODY) categories. Despite increasing awareness, its true prevalence remains largely underestimated. We describe a Portuguese cohort of individuals with suspected monogenic diabetes who were genetically evaluated for MODY-causing genes. METHODS: This single-center retrospective cohort study enrolled patients with positive genetic testing for MODY between 2015 and 2021. Automatic sequencing and, in case of initial negative results, next-generation sequencing were performed. Their clinical and molecular characteristics were described. RESULTS: Eighty individuals were included, 55 with likely pathogenic/pathogenic variants in one of the MODY genes and 25 MODY-positive family members, identified by cascade genetic testing. The median age at diabetes diagnosis was 23 years, with a median HbA1c of 6.5%. The most frequently mutated genes were identified in HNF1A (40%), GCK (34%) and HNF4A (13%), followed by PDX1, HNF1B, INS, KCNJ11 and APPL1. Thirty-six unique variants were found (29 missense and 7 frameshift variants), of which ten (28%) were novel. CONCLUSIONS: Our data highlights the importance of genetic testing in the diagnosis of MODY and the establishment of its subtypes, leading to more personalized treatment and follow-up strategies.

Pituitary adenomas in the elderly: Retrospective comparative analysis of clinical/tumor features and surgical data by age group.

The increase in life expectancy along with technological advances has translated into a higher number of pituitary adenomas (PA) diagnosed from the age of 65. In the elderly, symptoms related to comorbidities might overlap with endocrine dysfunction, in addition to increasing anesthetic and surgical risks. This study aimed to compare baseline clinical and tumor features between patients with PA from different age groups: younger adults (YA), 18 to 64 years, and older adults (OA), ≥65 years. As secondary outcomes, we also intended to assess: clinical characteristics and tumor features in patients undergoing surgical intervention and surgical data and complications in patients undergoing transphenoidal surgery (TSS). This retrospective cohort study included patients diagnosed with PA in adulthood divided into YA and OA groups. The secondary outcomes were evaluated in the subgroups: patients who underwent pituitary surgery and patients specifically submitted to TSS, who had completed postoperative follow-up ≥ 6 months until July/2020. A total of 401 patients were included, 327 (81.5%) in the YA and 74 (18.5%) in the OA group. Hormone-secreting effects were more common in the YA group (P < .001) and mass effects in the OA group (P = .070). The prevalence of hypertension and diabetes was higher in the OA group (P = .002, P = .011). A larger proportion of nonfunctioning (NF) PA and prolactinomas was found in OA (P < .001) and YA (P = .012), respectively. Macroadenomas were more common in the OA group (P < .001). No differences were found in terms of invasiveness. In the secondary outcome analysis, there was a higher prevalence of NF-PA in those who underwent pituitary surgery. The rate of TSS-related complications was similar between the groups for major, minor and endocrine/electrolyte complications. OA-PA clinically differ from the younger: tend to present more frequently with chronic comorbidities and less frequently with hormone-secreting effects, are more often NF and larger in size without a significant increase in invasiveness. The TSS results were reassuring, proving to be equally safe for the elderly.

A Rare Case of Thoracoabdominal Paraganglioma: A Case Report and Literature Review.

Pheochromocytomas and paragangliomas are rare neuroendocrine tumors. Pheochromocytomas are derived from chromaffin cells of the adrenal medulla, while paragangliomas arise from the extra-adrenal autonomic paraganglia. Paragangliomas can derive from either parasympathetic or sympathetic paraganglia. The majority of parasympathetic ganglia-derived paragangliomas are nonfunctional and symptoms arise from mass effect, while sympathetic paragangliomas are frequently functional and present with symptoms that result from catecholamine hypersecretion. Here, we present the case of a 19-year-old female with hypertension whose biochemical tests revealed elevated plasma and urinary levels of norepinephrine and normetanephrine. Imaging studies showed a left paravertebral mass which was surgically removed. Histopathology confirmed a paraganglioma. Total surgical resection remains the gold-standard treatment and a cure can be achieved; however, all tumors may harbor malignant potential, and a long-term biochemical and imaging follow-up is required in all patients. Screening for genetic germline mutations may be helpful in identifying patients with a higher risk of recurrence or of developing other primary tumors.

Predictors of metformin monotherapy failure in gestational diabetes mellitus.

Objective: Metformin has emerged as a safe and effective pharmacological alternative to insulin in gestational diabetes mellitus (GDM), being associated with lower maternal weight gain and hypoglycemia risk. Nevertheless, glycemic control is unaccomplished in a considerable proportion of women only treated with metformin. We aim to determine the metformin monotherapy failure rate in GDM and to identify predictors of its occurrence. Design and methods: This was a retrospective multicenter study including pregnant women with GDM patients who started metformin as a first-line pharmacological treatment (n = 2891). A comparative analysis of clinical and analytical data between the group of women treated with metformin monotherapy and those needing combined therapy with insulin was performed. Results: In 685 (23.7%) women with GDM, combined therapy to achieve adequate glycemic control was required. Higher pregestational BMI (OR 1.039; CI 95% 1.008-1.071; P-value = 0.013), higher fasting plasma glucose (PG) levels in oral glucose tolerance test (OGTT) (OR 1.047; CI 95% 1.028-1.066; P-value <0.001) and an earlier gestational age (GA) at metformin introduction (0.839; CI 95% 0.796-0.885, P-value < 0.001) were independent predictive factors for metformin monotherapy failure. The best predictive cutoff values were a fasting PG in OGTT ≥87 mg/dL and GA at metformin introduction ≤29 weeks. Conclusions: In 685 (23.7%) women, combined therapy with insulin to reach glycemic control was required. Higher pre-gestational BMI, fasting PG levels in OGTT ≥87 mg/dL and introduction of metformin ≤29 weeks of GA were independent predictive factors for metformin monotherapy failure. The early recognition of these characteristics can contribute to the establishment of individualized therapeutic strategies and attain better metabolic control during pregnancy.

Brain metastasis from calcitonin-negative medullary thyroid carcinoma.

INTRODUCTION: Medullary thyroid cancer (MTC) is a primary neuroendocrine tumor derived from parafollicular cells or C-cells of the thyroid gland. It accounts for 1% to 10% of all thyroid cancers and is the second most aggressive thyroid cancer after undifferentiated thyroid carcinoma. Serum calcitonin and carcinoembryonic antigen (CEA) concentrations are widely used as biomarkers to facilitate diagnosis and follow-up. However, in rare cases, serum levels of calcitonin or CEA can be normal. CASE PRESENTATION: We report the case of a 64-year-old male patient with MTC who presented brain metastasis and normal preoperative serum levels of calcitonin and CEA. The patient underwent total thyroidectomy with central compartment lymph-node dissection, resection of the single brain metastasis, and adjuvant holo-cranial radiotherapy. At 30 months' follow-up, he maintained normal serum calcitonin and CEA levels with increased procalcitonin levels. CONCLUSION: We describe a rare case of "calcitonin-negative" MTC with brain metastasis. The pathophysiology underlying normal serum levels of calcitonin in MTC is still not clearly understood. The lack of effective serum biomarkers for these patients makes diagnosis and treatment challenging.

Papillary thyroid carcinoma: the impact of histologic vascular invasion.

OBJECTIVE: The American Thyroid Association (ATA) recurrence risk prediction system considers vascular invasion (VI) as a relative indicator for adjuvant radioactive iodine (RAI) treatment, nevertheless VI final role in PTC management is yet to be defined. This study aims to assess the impact of histologic VI in PTC. METHODS: A retrospective study with PTC patients admitted in our Thyroid Cancer Unit, between January 1960 and December 2016 was performed. We reviewed 905 patient records with 275 having full information about VI on their pathological reports. Demographic and clinical variables were obtained, and univariate/multivariate analysis was performed in order to obtain potential predictive prognostic factors. RESULTS: Fifty-one out 275 patients presented VI (18.5%; 95% CI 14.4 - 23.6%), these individuals had larger tumors (median 19mm vs 12 mm, p < 0.001) with more frequent extraglandular invasion (54.0% vs 17.1%, p<0.001), regional lymph nodes involvement (29.8% vs 12.6%, p = 0.003)and distant metastasis (10.9% vs 1.9%, p = 0.003) at diagnosis. Vascular invasion was an independent predictor for regional lymph node and/or distant metastasis at diagnosis [OR 2.93 (IC95% 1.16 - 7.41, p = 0.008)]. After a median follow-up time was 68.5 months patients with VI presented higher rates of local recurrence and lymph node metastasis recurrence. CONCLUSIONS: In this study, the presence of VI in PTC is associated to higher rate of lymph node and distant metastasis at diagnosis. Its presence should be probably considered an adverse prognostic factor in PTC, perhaps justifying more aggressive therapeutic and follow-up approaches in such cases.

Gestational diabetes in twin pregnancy: A predictor of adverse fetomaternal outcomes?

AIM: To compare fetomaternal outcomes between GDM pregnant women with twin versus singleton pregnancies and then between women with GDM versus non-GDM twin pregnancies. METHODS: We performed a retrospective study including GDM pregnant women with both twin and singleton pregnancies followed in our tertiary center between 2011 and 2018. The fetomaternal characteristics of each group were compared. We then compared women with GDM twin pregnancy followed at our institution between 2011 and 2018 to non-GDM twin pregnant women giving childbirth in 2018. RESULTS: A total of 1127 GDM pregnant women were evaluated: 42 with twin pregnancy and 1085 with singleton pregnancy. Preeclampsia (14.3% vs. 3.3%, p < 0.001) and cesarean delivery (76.2% vs. 36.9%, p < 0.001) were more frequent among women with twin pregnancy. Neonatal morbidity was also more common among neonates delivered from twin pregnant women, including preterm labor (73.8% vs. 7.8%, p < 0.001), hypoglycemia (6% vs. 4.8%, p = 0.043), hyperbilirubinemia (33.3% vs. 9.0%, p < 0.001), RDS (28.6% vs. 2.7%, p < 0.001), admission in NICU (32.1% vs. 4.5%, p < 0.001) and SGA (19.0% vs. 11.0%, p = 0.001). Overall there were no significant differences in fetomaternal morbidity parameters between GDM (n = 42) versus non-GDM (n = 83) twin pregnancies, although SGA infants were more frequent in the latter group (33.9% vs. 19.0%, p = 0.014). CONCLUSIONS: In GDM pregnant women, twin pregnancy seems to be associated with an increased prevalence of neonatal morbidity when compared to singleton pregnancy. On the other hand, in twin pregnancy, diagnosis of GDM does not seem to be associated with poorer fetomaternal outcomes. GDM seems to be protective for the occurrence of SGA neonates in twin pregnancies.

Impact of intermittently scanned continuous glucose monitoring on quality of life and glycaemic control in persons with type 1 diabetes: A 12-month follow-up study in real life.

BACKGROUND AND AIM: We sought to prospectively assess the impact of intermittently scanned continuous glucose monitoring (isCGM) initiation in the glycaemic control and quality of life (QoL) in type 1 diabetes mellitus (T1DM) patients followed in real-live conditions. METHODS: Prospective, observational, cohort, single-centre and single-arm study conducted between September 2018 and March 2020, enrolling adults with T1DM with at least one year of diagnosis, interested in using isCGM. After training at isCGM initiation, CGM metrics and QoL were assessed at baseline and 12 months. RESULTS: Thirty-six individuals (55.6% male) were included; median age at inclusion was 49.0 (43.5-62.5)years and the mean(±SD) duration of T1DM was 25.5 ± 12.0 years. Median (interquartile range) HbA1c decreased from 7.6(7.0-8.7)% to 7.4(6.8-7.7)% at 12 months (p = 0.02), driven by the subgroup of individuals with baseline HbA1c ≥ 7.5%. The number of scans per day increased from 7.0(5.5-10.0) to 10.0(7.0-14.0) but no correlation was found between the number of daily scans and CGM metrics. Total daily insulin dose remained unchanged, however the proportion of basal insulin decreased, and the proportion of bolus insulin increased over time. Multiple QoL subscales scores improved significantly, including disease-burden subscale for which TIR proved to be a significant predictive factor. CONCLUSION: isCGM improved both glycaemic control, namely time in range, time below range and glycaemic variability, as well as QoL scores in the long term. The increase of the bolus insulin proportion suggests a behavioural change. However, the appraisal of our results must consider our substantial rate of drop-out limiting the external validity of our findings.

MODY probability calculator utility in individuals' selection for genetic testing: Its accuracy and performance.

INTRODUCTION: MODY probability calculator (MPC) represents an easy-to-use tool developed by Exeter University to help clinicians prioritize which individuals should be oriented to genetic testing. We aimed to assess the utility of MPC in a Portuguese cohort with early-onset monogenic diabetes. METHODS: This single-centre retrospective study enrolled 132 participants submitted to genetic testing between 2015 and 2020. Automatic sequencing and, in case of initial negative results, generation sequencing were performed. MODY probability was calculated using the probability calculator available online. Positive and negative predictive values (PPV and NPV, respectively), accuracy, sensitivity and specificity of the calculator were determined for this cohort. RESULTS: Seventy-three individuals were included according to inclusion criteria: 20 glucokinase (GCK-MODY); 16 hepatocyte nuclear factor 1A (HNF1A-MODY); 2 hepatocyte nuclear factor 4A (HNF4A-MODY) and 35 DM individuals with no monogenic mutations found. The median probability score of MODY was significantly higher in monogenic diabetes-positive subgroup (75.5% vs. 24.2%, p < .001). The discriminative accuracy of the calculator, as expressed by area under the curve, was 75% (95% CI: 64%-85%). In our cohort, the best cut-off value for the MODY calculator was found to be 36%, with a PPV of 74.4%, NPV of 73.5% and corresponding sensitivity and specificity of 76.2% and 71.4%, respectively. CONCLUSIONS: In a highly pre-selected group of probands qualified for genetic testing, the Exeter MODY probability calculator provided a useful tool in individuals' selection for genetic testing, with good discrimination ability under an optimal probability cut-off of 36%. Further geographical and population adjustments are warranted for general use.

Expression of PD-L1 in medullary thyroid carcinoma-a new therapeutic target?

PD-L1 expression in MTC is hot topic since, if it is demonstrated that PD-L1 is highly expressed in this cancer, thus immunotherapy against checkpoint inhibitors could become an important therapeutic tool in MTC treatment. To answer this question, we evaluated PD-L1 expression in MCT tumour tissues, using an anti-PD-L1 22C3 antibody and found a high expression in 6 of the 8 patients (75%). Similarly, two other recent studies reported a higher PD-L1 expression. According to our results, MTC cells present a significative PD-L1 expression, raising the hypothesis that immunotherapy, such as pembrolizumab, could have a role on MCT treatment. The authors believe this is a fundamental question and may impact the future of MTC treatment.