BACKGROUND/OBJECTIVES:Precise staging and tumor delineation are essential for optimizing treatment and enhancing outcomes of radiotherapy (RT). While computed tomography (CT)-based RT remains standard, fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) offers improved detection of primary and nodal disease. This study investigates the role of PET/CT in RT planning of HNSCC. METHODS:Fifty-one HNSCC patients underwent radical volumetric modulated arc RT with concurrent cisplatin chemotherapy in a prospective study. Two RT plans per patient were sequentially created by a single oncologist using CT-only and PET/CT data, respectively. Planning target volumes (PTVs) for primary and nodal regions were independently defined, and dose-volume histograms were analyzed and compared. RESULTS:PET/CT significantly affected TNM staging, increasing the T-stage in 11.8% of patients and the N-stage in 33.3%. Distant metastases were found in 9.8% of patients, leading to a redefinition of the overall treatment policy. PET/CT-based planning improved primary tumor PTV coverage (PTV4) in 37.2% (19/51) of cases. The tumor areas excluded from the CT-based planning received an average of 85.6% of the prescribed PTV4 dose (range 18-93%), while in PET/CT planning, they received 95.4% (range 93-99%) (p < 0.0001). Nodal PTV areas requiring a booster dose (PTV2) were adjusted in 33.3% (17/51) of patients during PET-CT planning. These nodal areas received an average of 85.6% of the prescribed dose for PTV2 (range 18-93%) during CT planning, compared to 95.4% (range 93-99%) during PET/CT planning. There was no statistically significant difference in the dose received by organs at risk between CT- and PET/CT-RT planning. CONCLUSIONS:PET/CT improves target delineation for primary tumors and lymph nodes, also allowing for dose escalation in metabolically highly active lesions in patients with HNSCC. The method also reveals occult distant metastases in a subset of patients, enabling personalized treatment strategies.

Objective: Diabetic polyneuropathy (DPN) is a common and disabling complication of type 2 diabetes mellitus (T2DM). Vitamin D deficiency has been implicated as a potential modifiable riskfactor. This study aimed to investigate the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and DPN using the radioimmunoassay (RIA) method. Subjects and Methods: One hundred twentyT2DM patients (80 with DPN and 40 without neuropathy) have been enrolled, while 40 healthy volunteers served as group control. Neuropathy diagnosis was based on clinical assessment (through Michigan neuropathy screening instrument (MNSI)-both questionnaire and examination) and nerve conduction studies. Serum 25(OH)D levels were quantified using RIA. Results: Vitamin D levels were significantly lower in DPN patients (mean 13.2ng/mL) compared to diabetic (18.3ng/mL) and healthy controls (31.2ng/mL, P<0.001). Vitamin D deficiency (<10ng/mL) was found in 72.5% of DPN patients. Apart from severe neuropathy, other factors (age, body mass index-BMI-and HbA1c) have all been mildly inversely correlated to Vitamin D levels. Conclusions: Vitamin D deficiency is significantly associated with the presence and severity of DPN.These findings support the clinical value of assessing and potentially improving vitamin D status in diabetic patients, particularly in those with severe neuropathy.

Purpose Vitamin D deficiency has been associated with the occurrence of obstructive sleep apnea syndrome (OSAS). Megalin ( LRP2 ) and cubilin ( CUBN) are implicated in vitamin D metabolism, whereas LRP2 and CUBN polymorphisms have been previously associated with variable serum vitamin D levels. The present study aimed to evaluate the role of LRP2 rs2228171 c.8614C > T and CUBN rs1801222 c.758A > G polymorphisms in OSAS susceptibility, independently or in synergy with vitamin D levels. Methods Vitamin D serum concentration of consecutive individuals was measured. PCR–RFLP was used for LRP2 rs2228171 and CUBN rs1801222 genotyping. Results A total of 176 individuals was enrolled, including 144 patients with OSAS and 32 controls. Frequency of LRP2 rs2228171 c.8614 T and CUBN rs1801222 c.758G alleles was estimated at 22.4% and 79.8%, respectively. LRP2 and CUBN polymorphisms were not associated with OSAS occurrence (rs2228171Τ allele: 22.9% in OSAS group vs. 20.3% in controls, p = 0.651; rs1801222A allele 19.4% in OSAS group vs. 23.4% in controls, p = 0.471). Frequency of CUBN rs1801222A allele carriers was increased in patients with moderate or severe OSAS compared to mild OSAS ( p = 0.028). Patients with OSAS homozygous for LRP2 CC and CUBN GG genotypes had lower vitamin D serum concentration compared to controls carrying the same genotype (18.0 vs 27.0 ng/mL, p = 0.006 and 19.0 vs 27.5 ng/mL, p = 0.007, respectively). Conclusion CUBN rs1801222 polymorphism may affect OSAS severity. Among other factors, low vitamin D concentration is associated with OSAS occurrence, irrespectively of LRP2 and CUBN polymorphisms.

Suspicion for Cardiac Amyloidosis (CA) led a 75-year-old male patient with fatigue, dyspnea, and palpitations to be subjected to scintigraphic myocardial investigation with technetium-99m-pyrophosphate (99mTc-PYP, or PYP scan) in order to distinguish transthyretin-related CA (ATTR) from the light-chain Amyloidosis (AL) form. A characteristic anamnesis of bilateral carpal tunnel syndrome, vertebral canal stenosis, and senile cataract, as well as laboratory, Electrocardiographic (ECG), and echocardiographic exploration was compatible with a positive for ATTR PYP scan. Specific features on PYP scan, namely Apical Sparing, more marked Septal Uptake and an associated Equivalent cardiac retention, particularly heart-to-contralateral (H/CL) Ratio from 1 h to 3 h pi (“ASSUMER”) were coupled with a negative genetic analysis, verifying wild-type ATTR. The herein introduced “ASSUMER” on PYP scan could be a hallmark not only of the amyloid fibril subtype but also origin.

BACKGROUND Carbohydrates as starch are a staple part of the Mediterranean diet. Starch is digested in the small intestine and the resulting glucose is absorbed into the blood, eliciting an insulin response. The digestion and absorption kinetics (rapid or slow) depends on starch structure. OBJECTIVE To study the relationship between the in vivo glycemic and insulinemic index and the in vitro digestibility characteristics of six bakery products, made from non-conventional wholemeal/wholegrain flours. METHODS We analyzed in vitro the rapidly- and slowly- available glucose (RAG and SAG), the rapidly- and slowly- digestible starch (RDS and SDS), and the resistant starch (RS) fraction of the six wholemeal/wholegrain products and one white type of bread. The glycemic and the insulinemic index (GI and II respectively) were estimated by in vivo testing in a group of eleven healthy individuals. RESULTS The GI of the wholemeal/wholegrain flour biscuits and breads were low, (range 28±3.2 to 41±3.9, Mean±SEM) correlating with the II. RAG positively correlated with both GI and II, with fiber having a marginal correlation. CONCLUSIONS Our findings indicate that both conventional and non-conventional wholemeal/wholegrain bakery products have low GI and moderate II, correlating to in vitro starch digestibility and the type of processing.

Cardiac amyloidosis is a rare condition characterized by the accumulation of abnormal proteins called amyloids in the heart tissue. These amyloids can disrupt the normal functioning of the heart and lead to a variety of symptoms and complications.

BACKGROUND: Carbohydrates as starch are a staple part of human diet. Upon starch digestion, glucose is absorbed, eliciting an insulin response. Glucose absorption kinetics (rapid or slow) depend on starch structure. Products made from wholemeal/wholegrain flour cause moderate glycemic and insulinemic responses and support a healthy lifestyle. OBJECTIVE: To review the nutritional value in terms of the in vivo glycemic and insulinemic index and the in vitro digestibility characteristics of six wholemeal/wholegrain commercial bakery products. METHODS: We analyzed in vitro the rapidly- and slowly- available glucose (RAG and SAG), the rapidly- and slowly- digestible starch (RDS and SDS), and the resistant starch (RS) fraction of the six wholemeal/wholegrain products against one white type of bread. The glycemic (GI) and the insulinemic index (II) were estimated in vivo in a group of eleven healthy individuals. RESULTS: The glycemic indices of the wholemeal/wholegrain flour biscuits and breads were low, (range 28 ± 3.2 to 41 ± 3.9, Mean+SEM) correlating with the insulinemic indices. RAG positively correlated with both GI and II, with fiber having a marginal correlation. CONCLUSIONS: Our findings indicate that both conventional and non-conventional wholemeal/wholegrain bakery products have low GI and moderate II, correlating to in vitro starch digestibility and type of processing.

Purpose: To describe the concordance of keratoconus (KC) expression in 2 pairs of monozygotic twins before and after a combined corneal crosslinking (CXL)/photorefractive keratectomy (PRK) procedure. Setting: Private ambulatory eye surgery unit. Design: Retrospective interventional twin study. Methods: Two pairs of male monozygotic twins with KC were studied retrospectively. Improvement of flattest (K1) and steepest (K2) keratometry, index of height decentration (IHD), and corneal thickness at the thinnest point and corneal epithelial thickness measured by anterior segment optical coherence tomography and Scheimpflug tomography was compared between respective eyes of monozygotic twin siblings 1 to 5 years after the application of combined CXL and topography-guided PRK of part of the refractive error (the Athens Protocol). Results: Significant improvement was noted in all the keratometric indices of all 8 eyes after the combined CXL/PRK procedure. The difference in K1, K2, IHD, corneal thickness at the thinnest point, and corneal epithelial thickness percentage improvement between the right eyes of each pair of twins was statistically significant 1 year and 5 years postoperatively ( P < .05). Statistically significant discordance in the aforementioned parameters percentage improvement was similarly observed between the left eyes of each pair of twins ( P < .05). Conclusions: Although a genetic predisposition in KC is well documented, the discordance in keratometric indices improvement after a CXL/PRK procedure between respective eyes of monozygotic twins suggests that environmental influences may contribute to the disease expression as well. Variable degree of synergy in a combined CXL/PRK procedure may also explain the aforementioned discordant improvement.

PURPOSE:Conventionally fractionated radiotherapy (CRT) is widely applied for the treatment of high-risk prostate cancer. Pelvic node irradiation improves control of the disease. Although the therapeutic guidelines support the use of hypofractionated and accelerated radiotherapy (HypoAR), this is addressed to prostate and seminal vesicles. At the same time, the safety and efficacy of HypoAR for pelvic node irradiation remain obscure. Material and Methods: In a phase II study, we evaluated the feasibility of pelvic HypoAR in 22 high-risk prostate cancer patients. The RT scheme delivers 14 consecutive fractions of 3.67 Gy (total 51.38 Gy) to the prostate, 3.5 Gy (total 49 Gy) to the seminal vesicles, and 2.7 Gy (total 37.8 Gy) to the lymph nodes, using image-guided volumetric modulated arc therapy. A comparative radiobiological analysis of dose-volume histogram is performed (HypoAR vs. hypothetical equivalent CRT regimens, without and with time correction).RESULTS:Our clinical experience shows impressively low early and short-term late toxicities, without any grade III events, within a median follow-up of 30 months. Only one biochemical relapse was recorded 30 months after irradiation. In radiobiological analysis, considering an α/β-value of 4 Gy and a λ-value of 0.2 Gy/day for late effects, all comparisons predicted significantly lower toxicity for the HypoAR regimen (p < 0.05). For early toxicities (α/β = 10 Gy), a λ-value lower than 0.4 Gy/day favors the HypoAR regimen, which is along with the clinical results.CONCLUSION:Radiobiological analysis favors HypoAR as a safe and effective regimen for high-risk prostate cancer patients, which is confirmed in the current phase II clinical study.

Background: COPD and OSA have been associated with low vitamin D (Vit D) serum levels but there are limited data regarding Vit D status in patients with coexistent COPD and OSA (overlap syndrome-OVS). Additionally, low vit D levels may be linked with increased cardiovascular risk and COPD exacerbations. Aim: The aim of the study was to compare Vit D serum levels between patients with OVS, patients with OSA and controls and to explore associations with anthropometric, respiratory and sleep parameters. Methods: Vit D serum levels [assessed by 25(OH)D levels] were measured in 3 prospectively recruited age-, gender-, and BMI-matched groups of patients with OVS, patients with OSA, and controls as verified by overnight polysomnography and PFTs. COPD diagnosis was based on symptoms and a post-bronchodilator FEV1/FVC<0.7; while OSA diagnosis was based on apnea-hypopnea index (AHI)≥5/h along with symptoms. Subjects with AHI<5/h and normal PFTs were considered as controls. Each group included 30 individuals. Results: Patients with OVS exhibited decreased serum 25(OH)D levels compared with OSA patients [14.5 (12.3–17.9) vs 18.6 (13.2–25.2) ng/ml respectively, p<0.05] and controls [21.6 (17.8–33.6) ng/ml, p<0.001]. Multiple linear regression analysis identified an association between AHI (β=-0.758, p=0.041) and FEV1 (β=0.698, p=0.038) with serum Vit D levels, in the OVS group. Conclusions: Patients with OVS exhibit significant lower Vit D levels; stronger predictors were AHI and FEV1. Given potential associations between Vit D deficiency and cardiovascular disease and COPD exacerbations, it may be useful its measurement and treatment; however more studies are needed.

BACKGROUND:153 The radionuclide samarium-153 ( Sm) in a chelated compound with ethylene-diamine-tetramethylene phosphonate(EDTMP) is mainly used as an alternative to palliative therapy of multifocal painful osseous metastases due to various primaries, especially153 prostate, breast, lung cancer, and osteosarcoma. Considering novel aspects of chemical properties attributed to Sm, we aimed at evaluating the153 outcomes of solitary versus repeated Sm-EDTMPor exclusive opiate therapy in patients with osseous secondaries from prostate cancer.MATERIALS AND METHODS: In the present retrospective study, we included three groups of patients with hormone-refractory prostatecancer (HRPC) and multiple painful osteoblastic or mixed secondaries conrmed by bone scintigraphy. Forty-three patients (Group A) received 2153 consecutive intravenous (i.v.) administrations of Sm-EDTMP (37 MBq/kg of body weight each), twelve patients (Group B) received a solitary153 i.v. dose Sm-EDTMP and 12 patients (Group C) used solely opiates due to exclusion criteria regarding radiometabolic therapy.RESULTS: 153 Pain palliation was reported by 90.7% of group Apatients after the second injection. The repeated dose of Sm-EDTMPimproved theduration of pain response to 24±6 versus 8±2 weeks of the single dose treatment plan, without signicant myelotoxicity. Group C patients wereconsidered as non-responders owing to increased pain score and consumption of analgesics.CONCLUSION: 153 Arepeated-dose Sm-EDTMPtreatment scheme consistently provides enhanced pain alleviation, thereby preserving quality of153 life in patients with skeletal metastases from HRPC. Interestingly, radiometabolic therapy with Sm-EDTMP effectuates tumouricidalimplications, thus upgrading a palliative agent to a disease theragnostics-targeted modier, with anticipated survival benet.

Background: The coexistence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) has been defined as overlap syndrome (OVS). Recently, a link between OSA, COPD and Vitamin D (Vit D) serum concentration was reported, however, evidence regarding Vit D status in patients with OVS is scarce. The aim of the present study was to evaluate Vit D serum levels and to explore the association of those levels with anthropometric, pulmonary function and sleep parameters in patients with OVS. Methods: Vit D serum levels were measured in patients diagnosed with OVS, as confirmed by overnight polysomnography and pulmonary function testing. Results: A total of 90 patients (79 males and 11 females) were included in the analysis. The patients were divided into three groups matched for age, gender, and BMI: the control group that included 30 patients (27 males and 3 females), the OSA group that included 30 patients (26 males and 4 females), and the OVS group that included 30 patients (26 males and 4 females). Patients with OVS exhibited decreased serum 25(OH)D levels compared with OSA patients and controls (14.5 vs. 18.6 vs. 21.6 ng/mL, p < 0.001). In the OVS group, multiple linear regression analysis identified AHI and FEV1, as predictors of serum 25(OH)D levels (p = 0.041 and p = 0.038, respectively). Conclusions: Lower Vit D levels have been observed in patients with OVS compared with OSA patients and non-apneic controls, indicating an increased risk of hypovitaminosis D in this population which might be associated with disease severity.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

PURPOSE:To define and compare the centration of the ablation effect in laser in situ keratomileusis (LASIK) with the corresponding effect in small-incision lenticule extraction (SMILE), in myopic laser vision correction to possibly explain the refractive performance differences noted between the two procedures in a contralateral eye study.SETTING:Private ambulatory eye surgery unit.DESIGN:Prospective randomized contralateral eye study.METHODS:In 22 consecutive patients (44 eyes), 1 eye was prospectively randomized to undergo myopic topography-guided LASIK treatment and the contralateral eye to undergo SMILE; digital image analysis of the achieved centration to the aimed corneal vertex was assessed for both procedures on perioperative Scheimpflug tangential curvature maps, using a proprietary digitized methodology.RESULTS:The radial displacement measured in micrometers in the above treated 44 eyes, between the attempted centration point on the corneal vertex vs the center of the measured effective anterior corneal curvature flattening was on average 130 ± 62 mm in the 22 eyes of LASIK group and 313 ± 144 mm in the 22 contralateral eyes of the SMILE group (P < .001).CONCLUSIONS:In this contralateral eye study, topography-guided myopic LASIK was found to achieve significantly better effective centration compared with myopic SMILE, in regard to digitally measured decentration of the effective refractive change achieved in the anterior corneal curvature from the corneal vertex. This may explain the previously reported superior visual outcomes in the LASIK group eyes when compared with the contralateral SMILE group eyes.

PURPOSE To compare attempted versus achieved corneal stromal thickness reduction in a consecutive case series of patients undergoing laser in situ keratomileusis (LASIK) in one eye and small incision lenticule extraction (SMILE) in the other eye. METHODS This prospective, randomized, contralateral eye study included 22 consecutive patients (44 eyes), one eye randomized to have myopic LASIK and the contralateral eye to have SMILE. Anterior segment optical coherence tomography was performed preoperatively and at 3 months postoperatively. For each of the treatment groups, the achieved maximum stromal thickness reduction was compared to the planned/attempted thickness. The deviation of planned versus achieved stromal thickness reduction was then compared between the two groups. RESULTS At 3 months postoperatively, LASIK had a lower difference between planned versus attempted stromal thickness reduction compared to SMILE (13.72 ± 14.45 vs 24.00 ± 19.45 µm, P = .03). Graphical analysis revealed this deviation to be exaggerated in higher myopic errors, when a higher maximum stromal reduction was planned. The mean stromal reduction thickness was 83.40 ± 29.52 µm achieved versus 97.13 ± 25.69 µm mean planned ablation depth in the LASIK group (P < .001) compared to 76.45 ± 29.69 µm achieved versus 100.45 ± 26.56 µm planned ablation depth in the SMILE group (P < .001). CONCLUSIONS LASIK had a significantly lower difference between planned versus achieved stromal thickness reduction when compared to SMILE (P = .03). This difference was more apparent in higher myopic corrections. [J Refract Surg. 2021;37(7):454-459.].

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)