Hospitalization of Patients With Diabetes Due to Ketoacidosis Before and After the Initiation of Sodium-Glucose Cotransporter-2 Inhibitors.

OBJECTIVE: Diabetic ketoacidosis (DKA) is a rare side effect related to sodium-glucose cotransporter-2 inhibitors (SGLT2I). This study investigated the incidence of people with diabetes hospitalized because of DKA after the implementation of SGLT2I (2015-2019), compared with the pre-SGLT2I era. METHODS: In this retrospective cohort study, medical records of all adult patients hospitalized with a diagnosis of DKA in a tertiary referral center from 2011-2019 were reviewed. The incidence of DKA was compared between the periods 2011-2014 and 2015-2019. Demographic and clinical data of patients hospitalized with DKA as well as SGLT2I use were extracted. RESULTS: During 2011-2019, there were 186 hospitalizations because of DKA. The rate of hospitalization was stable during 2011-2019 at 0.22% ± 0.04% (95% CI, 0.18-0.25). The clinical characteristics of people hospitalized with DKA in 2011-2014 were similar to those of people hospitalized during 2015-2019. Only 7 people (6.1%) in the 2015-2019 cohort had SGLT2I-related DKA, and their clinical characteristics were similar to those of the rest of the cohort. CONCLUSIONS: The rate of hospitalizations because of DKA remained stable before and 5 years after SGLT2I were implemented for the treatment of type 2 diabetes mellitus. Larger, multi-institutional studies with longer follow-ups are needed to study the effect of SGLT2I on the rate of hospitalizations because of DKA among people with diabetes. Although DKA events associated with SGLT2I are rare, they should be strongly considered in the differential diagnosis of people treated with these medications.

Influence of Fasting until Noon (Extended Postabsorptive State) on Clock Gene mRNA Expression and Regulation of Body Weight and Glucose Metabolism.

The trend of fasting until noon (omission or delayed breakfast) is increasingly prevalent in modern society. This eating pattern triggers discordance between endogenous circadian clock rhythms and the feeding/fasting cycle and is associated with an increased incidence of obesity and T2D. Although the underlying mechanism of this association is not well understood, growing evidence suggests that fasting until noon, also known as an "extended postabsorptive state", has the potential to cause a deleterious effect on clock gene expression and to disrupt regulation of body weight, postprandial and overall glycemia, skeletal muscle protein synthesis, and appetite, and may also lead to lower energy expenditure. This manuscript overviews the clock gene-controlled glucose metabolism during the active and resting phases and the consequences of postponing until noon the transition from postabsorptive to fed state on glucose metabolism, weight control, and energy expenditure. Finally, we will discuss the metabolic advantages of shifting more energy, carbohydrates (CH), and proteins to the early hours of the day.

Anemia in Patients With Diabetes and Prediabetes With Normal Kidney Function: Prevalence and Clinical Outcomes.

OBJECTIVE: Anemia is a known complication of diabetes mellitus (DM); however, its prevalence and prognostic relevance in patients with DM and pre-DM with normal kidney function have not been well defined. This study assessed the prevalence of anemia in patients with DM and pre-DM and evaluated its association with clinical outcomes during a 4-year follow-up period. METHODS: This retrospective analysis included patients with DM and pre-DM referred to the Meir Medical Center Endocrine Institute in 2015. Patients with an estimated glomerular filtration rate (eGFR) of <60 mL/min or any other recognized cause of anemia were excluded. The risk of developing microvascular or macrovascular complications or of death during the 4-year follow-up period was determined. RESULTS: A total of 622 patients (408 with DM and 214 with pre-DM) were included. The mean age of the patients was 64 ± 10.6 years, and 70% were women. The baseline hemoglobin A1C level was 7.1% ± 1.7% (54 mmol/mol), and the eGFR was 86.1 ± 15.3 mL/min. At the time of inclusion, 77 patients (19%) with DM and 23 (11%) with pre-DM had anemia (hemoglobin level 11.9 ± 0.8 and 11.8 ± 0.8 g/dL, respectively), compared with normal hemoglobin levels of 13.8 ± 0.9 and 13.7± 0.9 g/dL, respectively, in the others. A multivariable analysis demonstrated an inverse correlation between baseline hemoglobin (as a continuous variable) and mortality (P = .035), microvascular complications (P = .003), and eGFR decline (P < .001) but not between baseline hemoglobin and macrovascular complications (P = .567). CONCLUSION: This study found a significant prevalence of anemia unrelated to renal failure, both in patients with DM and pre-DM. Anemia in these patients is associated with the development of microvascular complications, eGFR decline, and mortality. These results underscore the need for intensive lifestyle and pharmacologic interventions in these patients.

Vitamin D diminishes the high platelet aggregation of type 2 diabetes mellitus patients.

Platelet activation is found in inflammatory conditions and implicated in the pathogenesis of chronic medical conditions, such as atherosclerosis, coronary vascular disease, cerebrovascular disease, and diabetes mellitus (DM). HbA1c is inversely related to vitamin D25 levels in individuals with and without DM. This study aimed to determine the relation between platelet aggregation, vitamin D and HbA1c among healthy individuals and those with Type 2 DM (T2DM). The direct effect of vitamin D1, 25 (calcitriol) on platelet aggregation was also investigated. The study included four groups: A. normoglycemic Control group: HbA1c<5.7%; B. Pre-diabetes (DM): 5.7% ≥ HbA1c ≤ 6.4%; C. DM on aspirin therapy: HbA1c>6.4%(+)Asp.; and D. DM not on aspirin therapy: HbA1c > 6.4%(-)Asp. Platelet aggregation was tested with and without calcitriol or saline pre-treatment, using collagen or adenosine diphosphate (ADP) as agonists. Platelet aggregation was higher in DM(-)Asp group compared to normoglycemic and DM(+)Asp, and higher, but not significant compared to pre-DM. The entire study population exhibited negative correlation between HbA1c and serum concentration of vitamin D25. Excluding DM(+)Asp, aggregation induced by collagen was significantly higher in patients with insufficient (<76 nmol/L) vitamin D25 compared to sufficient (≥76 nmol/L) vitamin D25. In this cohort, a negative correlation was found between serum concentrations of vitamin D25 and collagen-induced percent maximum (%max) aggregation and area under curve (AUC) aggregation. In the DM(-)Asp group, collagen-induced aggregation was reduced by approximately 25% after calcitriol treatment. Calcitriol decreased ADP-induced aggregation of control and DM(+)Asp groups to approximately 85% of saline treatment. We conclude that glycemic control is inversely associated with high platelet aggregation and low vitamin D25 levels. This elevated aggregation could be regulated by a novel, direct effect of calcitriol, indicating a beneficial effect of vitamin D on vascular complications related to diabetes. We offer a possible non-genomic mechanism for the vitamin D/Vitamin D receptor (VDR) pathway.

VARIATIONS IN CLINICAL AND IMAGING FINDINGS BY TIME OF DIAGNOSIS IN FEMALES WITH HYPOPITUITARISM ATTRIBUTED TO LYMPHOCYTIC HYPOPHYSITIS.

OBJECTIVE: To describe the various patterns of presentation, including assisting analyses, associated with the timing of diagnosis of females with hypopituitarism and suspected clinical diagnosis of lymphocytic hypophysitis. METHODS: A retrospective study of 9 consecutive females with pituitary dysfunction developed during or after pregnancy. All subjects were treated in our clinics between 2008 and 2014. Data were collected on clinical characteristics, pituitary hormone levels, and imaging findings. RESULTS: The study group included 9 patients with a mean age 33.7 ± 7.8 years at delivery. The probable cause of disease was lymphocytic hypophysitis. Headache or specific symptoms/signs of hypopituitarism appeared within 1 year of delivery. Five patients had headache, and 8 had difficulty breastfeeding or amenorrhea. Laboratory findings included central hypocortisolism (8/9 patients), hypogonadotropic hypogonadism (8/9), and central hypothyroidism (6/7). Insulin-like growth factor-1 (IGF-1) levels were low in 8/8 patients. Prolactin levels were low in 3/9 patients, and 1 patient had diabetes insipidus. Seven patients were diagnosed less than 1 year from symptom onset; 4 (57%) complained of headaches, and 5 (71%) had panhypopituitarism. Two patients were diagnosed later. Both had difficulty breastfeeding and amenorrhea, and one also had headaches. Both had panhypopituitarism and reduced pituitary volume. None of the patients fully recovered pituitary function. Normalization of the thyrotroph axis occurred in 3 patients, gonadotroph function in 3, the corticotroph axis in 2, and IGF-1 normalized in 1 subject. CONCLUSION: Hypopituitarism attributed to lymphocytic hypophysitis may present during pregnancy or early postpartum period with a clear clinical picture, or later, with indolent and nonspecific symptoms and signs.

Impaired decline in renal threshold for glucose during pregnancy - a possible novel mechanism for gestational diabetes mellitus.

BACKGROUND: The renal threshold for glucose (RT(G)) is determined by the nephron's reabsorptive capacity. Glucose is reabsorbed through sodium-coupled glucose cotransporters in the proximal tubules. During pregnancy, renal glucose reabsorptive capacity decreases, possibly, due to reduced glucose transporter expression. Our hypothesis is that inadequate decrease in RT(G) during pregnancy will make women more prone to develop gestational diabetes mellitus (GDM). METHODS: Pregnant women (n = 40) who were referred to our center for oral glucose tolerance test (OGTT) were included in the analysis. Plasma glucose levels and urinary glucose excretion were measured for 4 h after 100 g oral glucose load. These data were used to calculate RT(G) . The subjects were divided into two cohorts, GDM and non-GDM, according to the OGTT results. Mean RT(G) was compared between the two groups. RESULTS: Fifteen (37.5%) of the women were diagnosed with GDM. Seventeen participants had only trace amounts of urinary glucose excretion, and no value of RT(G) could be determined; RT(G) was determined in the other 23 subjects. Among these 23 women, 13 were diagnosed as GDM, and 10 had normal OGTT. RT(G) was lower in the non-GDM women (146 ± 14 mg/dL) than in the GDM women (182 ± 18 mg/dL), p < 0.001. CONCLUSIONS: Gestational diabetes mellitus is associated with higher RT(G) during pregnancy compared with non-GDM. These results support our hypothesis that inadequate decrease of the RT(G) may have a pathophysiological role in the development of GDM.

Clinical and pathologic characteristics of appendiceal neuroendocrine neoplasms diagnosed during pregnancy.

Introduction: Although appendicitis occurs in approximately 1:1000 pregnancies, appendiceal neuroendocrine neoplasm (ANEN) diagnosis during pregnancy is very rare. Data on presentation, treatment and prognosis is scarce. Aim: To describe ANEN cases diagnosed during pregnancy. Materials and methods: A retrospective appraisal of 7 consecutive ANEN patients diagnosed during pregnancy from four Israeli tertiary medical centers and comparison with 17 cases described in the literature from 1965-2021. Results: Age at ANEN diagnosis was 26.4 ± 3.5 years (range 21-33). Patients were diagnosed between gestational weeks 6-40, most frequently in the third trimester (53%). The most common presenting symptom was abdominal pain. Tumor size was 14.3 ± 8.9mm (range 3-45mm). In patients from our series appendiceal base involvement was reported in 2/7; mesoappendiceal invasion in 5/7; lympho-vascular invasion in 2/7. Ki67 staining was reported in 6/7 cases and ranged from 1-10%. Pathology details were lacking in most of the previously published cases. All 7 pregnancies in our series resulted in term delivery with no complications, whereas in historical cases there were one first trimester abortion, one ectopic pregnancy, and one stillbirth. Right hemicolectomy was performed in 5/7 patients in our series and reported in 2/17 historical cases. All hemicolectomies were performed after delivery, 3-16 months after appendectomy. Local metastases were reported in two cases. Follow-up duration was 7-98 months for our patients and 3-48 months in 5 historical cases. No disease recurrence, distant metastases or mortality were noted. Conclusions: To the best of our knowledge, this is the largest series describing the extremely rare diagnosis of ANEN during pregnancy. Although pathologic characteristics varied, pregnancy outcomes were usually favorable and long-term prognosis was excellent. This data may suggest that a conservative approach to patients with ANEN diagnosis during pregnancy can be considered.

Clinical characteristics of a large familial cohort with Medullary thyroid cancer and germline Cys618Arg RET mutation in an Israeli multicenter study.

Objective: To determine genealogical, clinical and pathological characteristics of a cohort with Cys618Arg mutation from an Israeli multicenter MTC study. Methods: Retrospective database analysis examining RET mutations and comparing Cys618Arg and Cys634Arg/Thr/Tyr subgroups. Results: Genetic testing was performed in 131/275 MTC patients (47.6%). RET mutations were found in 50/131 (38.2%), including Cys618Arg (28/50 cases,56%), and Cys634Arg/Thr/Tyr (15/50,30%). Through genealogical study, 31 MTC patients were found descendants of one family of Jewish Moroccan descent, accounting for 27/28 patients with documented Cys618Arg mutation and 4 patients without available genetic testing. Familial Cys618Arg cases (n=31) and Cys634Arg/Thr/Tyr cases (n=15, from 6 families) were compared. Although surgical age was similar (25.7 vs 31.3 years, p=0.19), the Cys618Arg group had smaller tumors (8.9mm vs 18.5mm, p=0.004) and lower calcitonin levels (33.9 vs 84.5 X/ULN, p=0.03). Youngest ages at MTC diagnosis were 8 and 3 years in Cys618Arg and Cys634Arg/Thr/Tyr cohorts, respectively. Long-term outcome was similar between groups. The Cys618Arg cohort had lower rates of pheochromocytoma (6.5% vs 53.3%, p=0.001) and primary hyperparathyroidism (3.2% vs 33.3%, p=0.01). Conclusion: This is the first description of RET mutation distribution in Israel. Of 131 tested MTC patients, Cys618Arg was the predominant mutation. To the best of our knowledge, this is the largest cohort of Cys618Arg mutation described. For Cys618Arg and Cys634Arg/Thr/Tyr cohorts, MTC was diagnosed earlier than expected, likely due to familial genetic screening, and MTC outcomes were similar between groups. International studies are necessary to further characterize the clinical features of Cys618 mutations due to their relative rarity.

A Comparison of Outcomes in Medullary Thyroid Carcinoma Patients With and Without a Preoperative Diagnosis: A Multicenter Retrospective Cohort Study.

Background: Cytological limitations pose a challenge to preoperative diagnosis of medullary thyroid carcinoma (MTC) and therefore, a significant subset of patients is only diagnosed postoperatively. The objective of this study was to investigate the impact of knowledge of a preoperative MTC diagnosis on disease management and outcomes. Methods: Multicenter, retrospective, cohort study of MTC patients treated in Israel from January 2000 to June 2021. We compared cohorts of patients according to the presence or absence of a preoperative MTC diagnosis. Results: Ninety-four patients with histologically confirmed MTC were included (mean age 56.2 ± 14.3 years, 43% males). Fifty-three patients (56%) had a preoperative MTC diagnosis (preop-Dx group), and 41 (44%) were confirmed only postoperatively (no-Dx group). The extent of surgical resection, including completion procedures, was as follows: total thyroidectomy in 83% versus 100% (p = 0.002), central lymph node dissection (LND) in 46% versus 98% (p < 0.001), ipsilateral lateral LND in 36% versus 79% (p < 0.001), and contralateral lateral LND in 17% versus 28% (NS), in the no-Dx versus the preop-Dx group, respectively. Pathology confirmed a smaller median tumor size of 16 ± 17.4 mm versus 23 ± 14.0 mm (p = 0.09), a higher proportion of micro-MTC (size ≤10 mm) 32% versus 15% (p = 0.03), and a higher rate of co-occurrence of follicular cell-derived carcinoma 24% versus 4% (p = 0.003), in the no-Dx compared to the preop-Dx group, respectively. The rates of extrathyroidal and extranodal tumor extension were not significantly different between the groups. At the last follow-up, the biochemical cure was attained in 55% [CI 0.38-0.71] compared to 64% [CI 0.50-0.77] of the no-Dx and the preop-Dx group, respectively (p = 0.41). After the exclusion of patients with micro-MTC, biochemical cure was more commonly achieved in the preop-Dx group (33% [CI 0.14-0.52] vs. 62% [CI 0.46-0.77], p = 0.04). Preop-Dx patients had improved overall survival compared to the no-Dx group (log-rank p = 0.04) over a median follow-up of 82 months (interquartile range [IQR] 30-153). Conclusions: Preoperatively, the diagnosis of MTC is often missed. An accurate preoperative diagnosis of MTC may enable guideline-concordant surgical treatment and ultimately contribute to an overall survival benefit in MTC patients.

Is there an added value for whole body scan combined with stimulated thyroglobulin testing for follow-up of differentiated thyroid cancer patients?

AIM: The aim of this study was to evaluate the incidence of positive WBS in patients with negative stimulated thyroglobulin (sTg), to define the clinical characteristics of this group, and the association with disease outcome. METHODS: DTC patients who underwent surveillance with simultaneous sTg and WBS were included. RESULTS: Two hundred seventy-two patients were included. Age at diagnosis was 46.5 ± 15.2 years, 79% were female. Mean duration of follow-up was 11.6 ± 6.8 years. Patients were categorised according to stimulation test results: sTg(-)/WBS(-) in 192/272 (70.6%); sTg(+) regardless of WBS results in 33/272 (12.1%); and sTg(-)/WBS(+) in 47/272 (17.3%) subjects. sTg > 10 mg/dl was considered positive. The three groups had similar demographic and pathologic characteristics. During follow-up, additional treatment was given in 77 patients (28.3%). Twelve (4.4%) developed distant metastases; 16 patients (5.8%) died. No deaths were disease-related. There was no difference in mortality rate between categories (P = 0.182). On multivariate analysis, additional treatment was associated with male gender (P = 0.046) and positive stimulation test results, either sTg (P < 0.001) or WBS (P < 0.001). Of the 47 WBS(+)/sTg(-) patients, 7(15%) were treated due to positive WBS results, including two who underwent additional surgery. CONCLUSION: A substantial proportion of stimulation test results were discordant. There was a significant association between WBS results and administration of additional treatment. Routine WBS had additional value for a small proportion of patients with no other evidence for disease and no indication for WBS.

Post-hip fracture rehabilitation outcomes of diabetic and non-diabetic elderly patients.

BACKGROUND: Although patients with diabetes mellitus (DM) are at higher risk of hip fracture, data regarding the effect of DM on rehabilitation outcomes are limited. METHODS: A retrospective single-centre study was conducted comparing elderly diabetic and non-diabetic patients with recent hip fracture, admitted to geriatric rehabilitation, 2014-2019. The functional independence measure (FIM) was used to assess physical and cognitive function. Delta-FIM was calculated by subtracting admission FIM from discharge FIM. One-year mortality, hospitalizations and fractures were assessed. RESULTS: Six-hundred-thirty elderly patients, post-hip fracture were included, mean age 83 ± 7 years, 70.5% (444) women. Among them, 193 (30.6%) had type 2 DM, HbA1c 6.6 ± 1.25%. They were younger (81.4 vs. 84.3 years, p < .01) and had more co-morbidities including hypertension, chronic kidney disease, ischaemic heart disease and cerebrovascular disease. Baseline cognitive and motor scores were similar between groups. Delta motor-FIM was similar between diabetics and non-diabetics (15.56 ± 8.95 and 14.78 ± 8.79, respectively, p = .35). Multivariate regression analysis showed motor-FIM improvement was associated with higher BMI, male sex, and younger age, but not with DM. Cognitive FIM did not change significantly during rehabilitation in either group. Similar rates of patients were discharged to nursing care facilities. There was no difference in 1-year hospitalization or fracture rates. One-year, all-cause mortality was higher among diabetic patients (10.9 vs. 6.6%, respectively, p = .07). After adjusting for covariates, DM was associated with higher mortality risk (odds ratio = 2.78, 95% CI [1.28, 6.04], p = .01). CONCLUSIONS: Patients with well-controlled DM have similar post-hip fracture rehabilitation potential compared with non-diabetics, despite more co-morbidities. These results support resource allocation for post-hip fracture rehabilitation among patients with DM. The higher 1-year all-cause mortality in patients with DM reinforces the need for close follow-up and control of co-morbidities in this population.

Efficacy and Safety of Intravenous Pamidronate for Parathyroid Hormone-dependent Hypercalcemia in Hospitalized Patients.

CONTEXT: Bisphosphonates are effective for hypercalcemia of malignancy (HOM). Efficacy and safety data for bisphosphonates in parathyroid hormone-related hypercalcemia (PTHRH) are rare, including pamidronate (Pam), which is not indicated for this condition. OBJECTIVE: This work aims to evaluate the efficacy and safety of Pam for moderate-to-severe PTHRH. METHODS: This retrospective case-control study was conducted at a tertiary care medical center. Patients included adults hospitalized with serum calcium levels greater than 12 mg/dL, from October 29, 2013 to December 17, 2019. Etiology was categorized as PTHRH or PTH-independent. Clinical and laboratory data of PTHRH patients treated with Pam (PTHRH-Pam+) were compared to Pam-untreated counterparts (PTHRH-Pam-). RESULTS: Thirty-four patients with 37 hospitalizations for PTHRH (Pam-treated and -untreated) met the inclusion criteria. Pam was given in 24 of 37 cases (64.8%). Admission serum calcium levels for the PTHRH-Pam+ group were higher than for PTHRH-Pam- group (14.4 mg/dL vs 13.0 mg/dL, P = .005). Median total Pam dose was 60 mg (range, 30-180 mg) in the treated group. Serum calcium decreased 3.5 mg/dL for PTHRH-Pam+ vs 1.6 mg/dL for PTHRH-Pam- (P = .003). No PTHRH-Pam+ patients developed hypocalcemia or acute kidney injury. Nadir serum phosphorus levels were lower in the PTHRH-Pam+ vs PTHRH-Pam- group (1.7 mg/dL vs 2.4 mg/dL, respectively, P = .004). Three PTHRH-Pam+ patients developed severe hypophosphatemia; all resolved with intravenous and oral supplementation. Seventeen patients underwent parathyroidectomy, of whom 10 received Pam within 28 days preoperatively. Postoperatively, 4 developed hypocalcemia and 3 hypophosphatemia. CONCLUSION: This study demonstrates that Pam is effective and safe for treating PTHRH, while ensuring close laboratory monitoring of calcium and phosphorus metabolism. Larger, prospective studies are needed to establish the role of Pam and other potent bisphosphonates in moderate-to-severe PTHRH.

Temporal trends in incidence, evaluation and management of neuroendocrine neoplasms of the appendix: 14 years' experience.

BACKGROUND: Information regarding temporal trends in appendiceal neuroendocrine neoplasms (ANEN) is limited. This retrospective study evaluated temporal trends in ANEN incidence and management over a 14-year period. METHODS: Appendectomy pathology reports from a single tertiary center were reviewed. RESULTS: During 2005-2018, 8327 appendectomies were performed and 57 ANENs were diagnosed (average age 31.7 ± 17 years; 70.2% women; 17.5% Arab ethnicity; and 22.8% < 18 years of age). The cohort was divided according to year of diagnosis (Period A 2005-2011; Period B 2012-2018). No differences were found in ANEN incidence (0.75% and 0.62%, respectively, p = 0.104), epidemiologic or pathologic characteristics between periods. In period B, pathology reports were more comprehensive and use of specific imaging and biochemical studies was more prevalent. Hemicolectomy rates and results were similar (8 in Period A, 7 in Period B, p = 0.925). All patients remained alive for the duration of follow-up. CONCLUSIONS: No temporal changes in epidemiological, clinical or pathological features of ANENs were noted. Although clinico-pathological evaluation was more detailed after 2011, there was no change in rates of hemicolectomy or disease prognosis.

Appendiceal tumor incidence and an in-depth look at appendiceal neuroendocrine neoplasm in a cohort of 8,162 appendectomies: Full dataset.

Data describing appendiceal tumor incidence and epidemiology is limited. We collated data from appendectomy pathology reports between 2005 and 2018 in our institution and examined patient epidemiological and appendectomy pathological features [1]. Overall, 8,328 appendectomies were performed at our institution over the pre-specified time period and 8,162 patients had sufficient epidemiological data to be included in the analysis. A total of 153 patients (1.9%) were diagnosed with appendiceal tumors, of which 57 (37.3%) were Appendiceal Neuroendocrine Neoplasm (ANEN), 35 (22.9%) were mucinous cystadenoma and 34 (22.2%) ovarian cancer metastases. We further examined the ANEN cases in order to characterize initial patient and tumor characteristics, to evaluate the performance of further investigations and interventions, and ultimately to study the behavior of these tumors over time.

The prognostic value of lymph node ratio in Medullary thyroid carcinoma: A multi-center study.

INTRODUCTION: The lymph node ratio (LNR), which represents the proportion of metastatic lymph nodes resected, has been found to be a prognostic variable in several cancers, but data for Medullary thyroid carcinoma (MTC) are sparse. The aim of this study was to determine the value of the LNR in predicting outcome in patients with MTC. MATERIALS AND METHODS: A retrospective multicenter study design of 107 patients with MTC who underwent total thyroidectomy with neck dissection between 1984 and 2016. The association of LNR with patient and tumor characteristics and prognostic factors was evaluated. RESULTS: Study population consisted of 53.3% female, mean age at diagnosis was 50.3 ± 18.4 years; 16.8% had inherited MTC. LNR was positively correlated with tumor size (p = 0.018) and inversely correlated with age at diagnosis (p = 0.024). A higher LNR was associated with extrathyroidal extension (p < 0.001), multifocality (p = 0.001), bilateral tumor (p = 0.002), distant metastases (p < 0.001), and tumor recurrence (OR = 14.7, p < 0.001). LNR was also correlated to postoperative calcitonin levels (p < 0.001) and carcinoembryonic antigen (p = 0.011). LNR >0.1 was associated with shorter disease-specific survival in patients at risk: tumor larger than 20 mm at diagnosis (p = 0.013), sporadic MTC (p = 0.01), and age above 40 years at diagnosis (p = 0.004). Cox multivariate survival analysis revealed LNR as the only significant independent factor for disease free survival (p = 0.005). CONCLUSIONS: This study showed that LNR correlates well with patient and tumor characteristics and prognostic variables. We suggest that LNR should be considered an important parameter for predicting outcome in MTC.

Management of Asymptomatic Sporadic Nonfunctioning Pancreatic Neuroendocrine Neoplasms (ASPEN) ≤2 cm: Study Protocol for a Prospective Observational Study.

Introduction: The optimal treatment for small, asymptomatic, nonfunctioning pancreatic neuroendocrine neoplasms (NF-PanNEN) is still controversial. European Neuroendocrine Tumor Society (ENETS) guidelines recommend a watchful strategy for asymptomatic NF-PanNEN <2 cm of diameter. Several retrospective series demonstrated that a non-operative management is safe and feasible, but no prospective studies are available. Aim of the ASPEN study is to evaluate the optimal management of asymptomatic NF-PanNEN ≤2 cm comparing active surveillance and surgery. Methods: ASPEN is a prospective international observational multicentric cohort study supported by ENETS. The study is registered in ClinicalTrials.gov with the identification code NCT03084770. Based on the incidence of NF-PanNEN the number of expected patients to be enrolled in the ASPEN study is 1,000 during the study period (2017-2022). Primary endpoint is disease/progression-free survival, defined as the time from study enrolment to the first evidence of progression (active surveillance group) or recurrence of disease (surgery group) or death from disease. Inclusion criteria are: age >18 years, the presence of asymptomatic sporadic NF-PanNEN ≤2 cm proven by a positive fine-needle aspiration (FNA) or by the presence of a measurable nodule on high-quality imaging techniques that is positive at 68Gallium DOTATOC-PET scan. Conclusion: The ASPEN study is designed to investigate if an active surveillance of asymptomatic NF-PanNEN ≤2 cm is safe as compared to surgical approach.

The "combined team" transition clinic model in endocrinology results in high adherence rates and patient satisfaction.

Background A structured transition process for young adults with chronic medical conditions from pediatric to adult clinics is strongly promoted. However, the most appropriate transition model has not yet been determined. This study evaluated the effect of a "combined team" Endocrinology Transition Clinic model, including a joint meeting with the patient and pediatric and adult endocrinologists, regarding medical treatment, adherence to follow-up and patient satisfaction with the process. Methods Clinical and demographic data of patients admitted to the Endocrinology Transition Clinic were collected. The clinical impact of the transition meeting was evaluated based on treatment modifications and patient adherence to follow-up. Patient satisfaction was evaluated using a questionnaire. Results From September 2014 through November 2018, 107 patients attended the Endocrinology Transition Clinic, 85.0% were females, mean age 19.7 ± 2.2 years (range 16-29), 97.2% were unmarried. The most common endocrine disorders were obesity (41.1%), Hashimoto's thyroiditis (41.1%) and ovarian hyperandrogenism (38.3%). The Transition Clinic visit modified treatment and/or evaluation for 48 (44.8%) patients. Adherence to follow-up in the adult clinic was 82.9% and was not associated with gender (p = 0.366), ethnicity (p = 0.725), age at transition (p = 0.479) or obesity (p = 0.375). Overall satisfaction reported by 65/85 patients was high (86.8%), although higher among patients who were adherent to follow-up (89.4% vs. 65.6%, p = 0.006). Conclusions The "combined team" transition model in endocrinology requires relatively few resources and has considerable clinical impact, high adherence to follow-up and high patient satisfaction rate. Implementing this model at the interface of pediatric and adult endocrinology units, and possibly in other medical fields, is feasible and efficient.

Patients' knowledge and opinions regarding osteoporosis, osteoporosis treatment, and oral health care.

BACKGROUND: In this study, the authors assessed the knowledge and opinions of patients regarding osteoporosis and the associations among osteoporosis, osteoporosis treatments, and oral health care use. METHODS: Outpatients with osteopenia or osteoporosis completed a questionnaire, including sociodemographic data, internet use, osteoporosis status, oral health care use status, and knowledge regarding the effect of osteoporosis pharmacotherapy on dental procedures. RESULTS: Among 258 patients (mean [standard deviation] age, 68.5 [9.3] years; 93% female), 83.9% had osteoporosis, one-third had previous osteoporotic fracture, and 74.4% took osteoporosis medication, mostly antiresorptive agents. In addition, 66.3% had more than 12 years of education, and 53.9% used the internet daily. A total of 79.9% visited a dentist during the past year, and 29.0% had undergone an invasive procedure. Yet 46.5% estimated that their dentist did not know that they had osteoporosis. Approximately one-half of the participants responded that they did not know the answers to knowledge questions regarding associations between osteoporosis, its pharmacotherapy, and oral health care. Of the patients who answered questions about associations between osteoporosis and oral health care, 70% incorrectly believed osteoporosis increased gingival disease, and 30% incorrectly thought medications should be discontinued before caries restoration. CONCLUSIONS: Outpatients with osteoporosis or osteopenia who responded to a questionnaire had limited knowledge about associations among osteoporosis, osteoporotic treatment, and oral health care. PRACTICE IMPLICATIONS: Dentists should review previous and current medical treatments with their patients, including osteoporosis diagnoses. The medical community should make more efforts to provide balanced, accurate information to help patients prioritize health care treatment and avoid unnecessary interruptions in osteoporosis treatment.

A RETROPERITONEAL SEMINOMA WITH ENTRAPPED NERVE GANGLION MASQUERADING AS A PARAGANGLIOMA.

OBJECTIVE: The differential diagnosis of retroperito-neal tumors includes lymphoid, germ cell, and neurogenic tumors such as paraganglioma. Paragangliomas are rare neuroendocrine tumors of the autonomic nervous system, which may secrete catecholamines and their metabolites. Clinical features include sustained or paroxysmal hypertension, headaches, sweating, and palpitations. Here we present an unusual case of a retroperitoneal tumor entrapping a sympathetic nerve ganglion and mimicking paraganglioma. METHODS: A 57-year-old man with a history of controlled hypertension presented with paroxysms of tachycardia, flushing, high blood pressure, and headache. Ambulatory blood pressure monitoring showed uncontrolled labile hypertension with a normal nocturnal dip. Abdominal computed tomography (CT) demonstrated a 6.1 cm mass in the right retroperitoneum with adjacent lymphadenopathy. Paraganglioma was suspected and 24-hour urine demonstrated elevated normetanephrines (575 mcg/24 hours; normal, 5 to 290 mcg/24 hours) and vanillylmandelic acid (8.3 mg/24 hours; normal, 0.5 to 6.6 mg/24 hours). 68-Gallium DOTATATE positron emission tomography/CT showed weak uptake in the retroperitoneal mass and no other mass lesions. RESULTS: Following preparation with alpha-adrenergic blockers, surgical excision was performed with diagnostic and curative intent. Postoperatively, hypertension and paroxysmal symptoms resolved completely. The histopathology report described seminoma with an entrapped large ganglion within the tumor. CONCLUSION: We describe a retroperitoneal seminoma with an entrapped ganglion causing hypertension and paroxysmal symptoms, with laboratory and imaging features compatible with paraganglioma. Awareness of the rare possibility of mechanical pressure on a ganglion, within the differential diagnosis of retroperitoneal mass and sympathetic symptoms may aid in clinical decision making in atypical cases.