The Prevalence of Hypomagnesemia in Hospitalized Type 2 Diabetic Patients Treated with Diuretics and/or Proton Pump Inhibitors.

BACKGROUND: Hypomagnesemia (serum magnesium level < 1.7 mg/dl) occurs more frequently in patients with type 2 diabetes mellitus (T2DM).Serum magnesium levels are not routinely tested in hospitalized patients, including in hospitalized patients with T2DM. OBJECTIVES: To evaluate the prevalence of hypomagnesemia among hospitalized T2DM patients treated with proton pump inhibitors (PPIs) and/or diuretics. METHODS: A total of 263 T2DM patients hospitalized in general departments were included in the study and were further divided into four groups: group 1 (patients not treated with PPIs or diuretics), group 2 (patients treated with PPIs), group 3 (patients treated with diuretics), and group 4 (patients treated with both PPIs and diuretics).  Blood and urine samples were taken during the first 24 hours of admission. Electrocardiogram was performed on admission. RESULTS: Of the 263 T2DM patients, 58 (22.1%) had hypomagnesemia (serum magnesium level < 1.7 mg/dl). Patients in group 2 had the lowest mean serum magnesium level (1.79 mg/dl ± 0.27). Relatively more patients with hypomagnesemia were found in group 2 compared to the other groups, although a statistically significant difference was not observed. Significantly more patients in group 3 and 4 had chronic renal failure. Patients with hypomagnesemia had significantly lower serum calcium levels. CONCLUSIONS: Hospitalized T2DM patients under PPI therapy are at risk for hypomagnesemia and hypocalcemia.

A 2017 SURVEY OF THE CLINICAL PRACTICE PATTERNS IN THE MANAGEMENT OF RELAPSING GRAVES DISEASE.

OBJECTIVE: Previous surveys from different world regions have demonstrated variations in the clinical management of Graves disease (GD). We aimed to investigate the clinical approach to GD relapse among endocrinologists. METHODS: Electronic questionnaires were e-mailed to all members of the Israeli Endocrine Society. Questionnaires included demographic data and different scenarios regarding treatment and follow-up of patients with GD relapse. RESULTS: The response rate was 49.4% (98/198). For a young male with GD relapse, 68% would restart antithyroid drug (ATD) (98% methimazole), while 32% would refer to radioactive iodine (RAI) treatment. Endocrinologists who treat >10 thyroid patients a week tended to choose ATDs over RAI ( P = .04). In the case of GD relapse with ophthalmopathy, 50% would continue ATDs, whereas 22.4% would recommend RAI treatment and 27.6% surgery. Most endocrinologists (56%) would continue ATDs for 12 to 24 months. Seventy-five percent would monitor complete blood count and liver function (39% for the first month and 36% for 6 months), and 44% would recommend a routine neck ultrasound. In a case of thyrotoxicosis due to a 3-cm hot nodule, most endocrinologists (70%) would refer to RAI ablation, 46.4% without and 23.7% with a previous fine-needle aspiration. No significant differences were found regarding gender, year of board certification, or work environment. CONCLUSION: Our survey demonstrates diverging patterns in the diagnosis and management of GD relapse that correlate well with previous surveys from other countries on GD-naïve patients and a less than optimal adherence to recently published clinical guidelines. ABBREVIATIONS: ATA = American Thyroid Association; ATD = antithyroid drug; CBC = complete blood count; GD = Graves disease; GO = Graves ophthalmopathy; LFT = liver function test; MMI = methimazole; PTU = propylthiouracil; RAI = radioactive iodine; TSI = thyroid-stimulating immunoglobulin.

Effect of pre-gestational weight and gestational weight gain in women with gestational diabetes controlled with medication on pregnancy outcomes - is recommended weight gain too liberal?

This is a retrospective cohort study of women with GDM treated with glucose-lowering agents that were followed and gave birth between 2005 and 2015 in the Assaf Harofeh medical center, Israel. Classification and regression tree method identified four groups according to adverse outcomes, consisted of 74 women with pre-gestational BMI below 25, 98 women with BMI 25-31, 90 women 31-39 and 18 women above 39. Respectively, median GWG was 12 kg (8-16), 11 kg (8-15), 7.5 kg (3.75-11) and 5 kg (-1.5 to 11.5) (p < .001). The risk for composite adverse outcomes was higher in the groups of BMI 25-31 (73.5%) and 31-39 (83.3%) in comparison to BMI <25 (51.4%) and 39 < (55.6%), p < .001. In women with pre-gestational BMI of <25, GWG of more than the median resulted in odds ratio of 2.75 (1.07-7.08, p = .036) for adverse pregnancy outcomes compared with participants who gained less than the median. Maternal obesity is related to adverse pregnancy outcomes. Women with GDM with normal pre-gestational BMI who gained weight according to IOM recommendations still experienced adverse outcomes.

Adherence to ATA 2015 guidelines in the management of unifocal non-invasive papillary thyroid cancer: a clinical survey among endocrinologists and surgeons.

BACKGROUND: Despite updated guidelines, management of thyroid nodules remains controversial. We aim to check implementation of new guidelines by ear-nose-throat (ENT) surgeons and endocrinologists. METHODS: A questionnaire was e-mailed including demographic data and an index case: a healthy 26-year-old women with a 3-cm Bethesda III (B3) atypia of undetermined significance solitary nodule and eventually papillary thyroid cancer (PTC). RESULTS: Respondent rate was 50.5%, 93 endocrinologists, 55 surgeons. For this case, 77.4% would repeat fine-needle aspiration (FNA), 25.3% order molecular analysis and 22.6% do surgery. If repeated FNA remained B3, 51% would choose surgery, 17.3% molecular analysis and 31.6% follow-up only. If repeated FNA was B6, 58.5% would recommend total (TTx) and 41.5% hemithyroidectomy (HTx). In pathologically confirmed PTC after HTx, 42.4% would recommend completion, 26.8% radioactive iodine (RAI) treatment. For a > = 4-cm tumor, 49.2% would recommend TTx. For a tumor 2-4 cm, 41% would recommend TTx. Variables favoring TTx were family history and radiation exposure. Only 17.4% would prefer TTx when small benign contralateral tumor is present. Reassessment at 1 year with undetectable thyroglobulin (Tg) included stimulated Tg (stTg) (72.5%), neck US only (27.5%) and combined US-stTg (59.4%); only 10.3% would order a diagnostic scan. For recurrence in two (13-9 mm) lymph nodes, 59.3% recommend reoperation, 16.3% RAI and 24.4% active surveillance. There were no major differences between endocrinologists and ENT surgeons. CONCLUSIONS: We report a considerable lack of adherence to new guidelines, with only 50% recommending HTx for a 4-cm unifocal low-risk PTC tumor.

Short-term Adherence with Discharge Recommendation for Insulin Treatment among Patients with Type 2 Diabetes.

BACKGROUND: Basal-bolus (BB) insulin treatment is increasingly used in poorly controlled diabetes patients during hospitalization and is commonly recommended at discharge; however, the extent of adherence with this recommendation is unknown. OBJECTIVES: To determine short-term adherence of type 2 diabetes mellitus (T2DM) patients discharged from internal medicine wards with recommendation for BB insulin treatment. METHODS: Prescription (primary physician adherence) and purchase (patient adherence) of long-acting and short-acting insulins during the first month following discharge from internal medicine wards was determined in 153 T2DM patients. Adherence was defined as full if prescription/purchase of both basal (long-acting) and bolus (short-acting) insulin was completed, and as partial if only one kind of insulin (basal or bolus) was prescribed/purchased. Association between demographic and clinical parameters and adherence was determined. RESULTS: Full adherence with discharge instructions was higher for primary physicians than for patients )79.1% vs. 69.3%, respectively, P = 0.0182). Pre-hospitalization hemoglobin A1C was significantly associated with adherence by both patients and primary physicians (full-adherence group 9.04% ± 2.04%; no-adherence group 7.51% ± 1.35%, P = 0.002). Age was negatively associated with adherence of both primary physicians and patients; however, this association did not reach statistical significance. Patients with certain background diseases such as atrial fibrillation, coronary heart disease, and chronic heart failure had significantly worse adherence (P < 0.05). When the sole cause of admission was diabetes, full adherence (100%) of both primary physicians and patients was found. CONCLUSIONS: Short-term adherence with discharge recommendation for BB insulin treatment is associated with pre-hospitalization patient characteristics.

Thyroid Disease in Pregnancy: A Clinical Survey among Endocrinologists, Gynecologists, and Obstetricians in Israel.

OBJECTIVES: To study the current practices in the management of subclinical hypothyroidism (SCH) and thyroid nodules during pregnancy of obstetricians/gynecologists (OB/GYNs) and endocrinologists in Israel. METHODS: An electronic questionnaire was sent by email to all members of the Israeli Endocrine Society and the Israel Society of Obstetrics and Gynecology. Questionnaires included demographic data and clinical scenarios with questions regarding the screening and management of pregnant women with SCH, hypothyroxinemia, and a palpable thyroid nodule. The questionnaire for OB/GYNs was slightly modified. RESULTS: We received 90 responses from endocrinologists and 42 responses from OB/GYNs. Among endocrinologists, 39% would repeat a thyroid-stimulating hormone (TSH) test of 2.9 mU/L with normal free thyroxine and treat with thyroxine if the second result was above 2.5 mU/L. Among OB/GYNs, 73% would manage a woman with SCH at the beginning of her pregnancy by themselves and only 22% would start thyroxine after a first TSH result above 2.5 mU/L. Concerning screening, 57% endocrinologists and 71% OB/GYNs recommended screening for thyroid dysfunction in every woman at the beginning of her pregnancy. Among endocrinologists, 54% would order an ultrasound for a palpable thyroid nodule and perform a fine needle aspiration only for suspicious lesions. CONCLUSIONS: The medical approach to thyroid disease in pregnant women remains a matter of controversy. Our results support the need for larger and prospective clinical studies.

[NEW TREATMENTS IN DIABETES MELLITUS - AN UPDATE].

INTRODUCTION: Diabetes is one of the most common chronic diseases. Most patients with type 2 diabetes are obese, and the global epidemic of obesity largely explains the dramatic increase in the incidence and prevalence of type 2 diabetes over the past 20 years. In the last decade intensive research has brought about an enormous change in the clinical approach to diabetes treatment. In this review we briefly discuss the main changes in diabetes treatment, such as new medications, bariatric surgeries and technology innovations. We hope that this short review would urge the reader to expand his knowledge on the subject.

Metformin Does Not Induce Hyperlactatemia in Patients Admitted to Internal Medicine Ward.

BACKGROUND: Concerns about metformin-associated lactic acidosis (MALA) prohibit the use of metformin in a large subset of diabetic patients, mostly in patients with chronic kidney disease. Increasing evidence suggests that the current safety regulations may be overly restrictive. OBJECTIVES: To examine the association between chronic metformin treatment and lactate level in acute illness on the first day of admission to an internal medicine ward. METHODS: We compared diabetic and non-diabetic hospitalized patients treated or not treated with metformin in different sets of kidney function. RESULTS: A total of 140 patients participated in the study, 54 diabetic patients on chronic metformin treatment, 33 diabetic patients without metformin and 53 patients with no diabetes. Most participants were admitted for conditions that prohibit metformin use, such as heart failure, hypoxia and sepsis. Average lactate level was significantly higher in the diabetes + metformin group compared to the diabetes non-metformin group. Metformin treatment was not associated with higher than normal lactate level (hyperlactatemia) or low pH. No patient was hospitalized for lactic acidosis as the main diagnosis. CONCLUSIONS: Chronic metformin treatment mildly increases lactate level, but does not induce hyperlactatemia or lactic acidosis in acute illness on the first day of admission to an internal medicine ward. These data support the expansion of metformin use.

The role of mouse Akt2 in insulin-dependent suppression of adipocyte lipolysis in vivo.

AIM/HYPOTHESIS: The release of fatty acids from adipocytes, i.e. lipolysis, is maintained under tight control, primarily by the opposing actions of catecholamines and insulin. A widely accepted model is that insulin antagonises catecholamine-dependent lipolysis through phosphorylation and activation of cAMP phosphodiesterase 3B (PDE3B) by the serine-threonine protein kinase Akt (protein kinase B). Recently, this hypothesis has been challenged, as in cultured adipocytes insulin appears, under some conditions, to suppress lipolysis independently of Akt. METHODS: To address the requirement for Akt2, the predominant isoform expressed in classic insulin target tissues, in the suppression of fatty acid release in vivo, we assessed lipolysis in mice lacking Akt2. RESULTS: In the fed state and following an oral glucose challenge, Akt2 null mice were glucose intolerant and hyperinsulinaemic, but nonetheless exhibited normal serum NEFA and glycerol levels, suggestive of normal suppression of lipolysis. Furthermore, insulin partially inhibited lipolysis in Akt2 null mice during an insulin tolerance test (ITT) and hyperinsulinaemic-euglycaemic clamp, respectively. In support of these in vivo observations, insulin antagonised catecholamine-induced lipolysis in primary brown fat adipocytes from Akt2-deficient mice. CONCLUSIONS/INTERPRETATION: These data suggest that suppression of lipolysis by insulin in hyperinsulinaemic states can take place in the absence of Akt2.

Aiming for better glucose control: is HbA(1c) of 7% the 'holy grail'? The clinical approach or seven clinical questions about 7.

The diabetes epidemic imposes a substantial burden on health systems and economy all over the world. Over the last two decades, many health systems adopted health care quality and performance measures for diabetes mellitus, most notably haemoglobin A(1c). This article raises concerns regarding the significance of HbA(1c) as a performance measure and emphasizes the need for individualized therapy.

Interpreting the results of the Semmes-Weinstein monofilament test: accounting for false-positive answers in the international consensus on the diabetic foot protocol by a new model.

AIMS: The Semmes-Weinstein monofilament is the most widely used test to diagnose the loss of protective sensation. The commonly used protocol of the International Consensus on the Diabetic Foot includes a 'sham' application that allows for false-positive answers. We sought to study the heretofore unexamined significance of false-positive answers. METHODS: Forty-five patients with diabetes and a history of pedal ulceration (Group I) and 81 patients with diabetes but no history of ulceration (Group II) were studied. The three original sites of the International Consensus on the Diabetic Foot at the hallux, 1st metatarsal and 5th metatarsal areas were used. At each location, the test was performed three times: 2 actual and 1 "sham" applications. Scores were graded from 0 to 3 based upon correct responses. Determination of loss of protective sensation was performed with and without calculating a false-positive answer as a minus 1 score. RESULTS: False-positive responses were found in a significant percentage of patients with and without history of ulceration. Introducing false-positive results as minus 1 into the test outcome significantly increased the number of patients diagnosed with loss of protective sensation in both groups. CONCLUSIONS: False-positive answers can significantly affect Semmes-Weinstein monofilament test results and the diagnosis of LOPS. A model that accounts for false-positive answers is offered.

Pilot study on the significance of random intrasite placement of the Semmes-Weinstein monofilament.

BACKGROUND: The possible effect of random intrasite placement on the outcome of the Semmes-Weinstein monofilament (SWF) test is not known. We sought to determine the significance of this variable in the diagnosis of loss of protective sensation (LOPS) in patients with diabetes. METHODS: Forty-five patients with diabetes with history of pedal ulceration (group 1), 81 patients with diabetes without history of ulceration (group 2) and 21 non-diabetic controls (group 3) were studied. The three original sites of the International Consensus on the Diabetic Foot at the hallux, first and fifth sub-metatarsal areas were divided into peripheral and interior zones resulting in a total of six zones. RESULTS: Mean total scores of monofilament test were significantly lower in peripheral zones as compared with interior zones of both feet in all three groups and affected the resulting percentage of loss of protective sensation. CONCLUSIONS: Intrasite monofilament placement can significantly affect monofilament test results and the diagnosis of loss of protective sensation. A model that corrects the effect of random intrasite placement is needed.

The effect of over- and undertreatment of hypothyroidism on hospitalization outcomes of patients with decompensated heart failure.

The effect of over- and undertreatment of hypothyroidism on hospitalization outcomes of patients with acute decompensated heart failure (HF) has not been evaluated yet. We conducted retrospective cohort analyses of outcomes among 231 consecutive patients with treated hypothyroidism who were admitted to internal medicine departments of Shamir Medical Center with HF (2011-2019). Patients were divided into three groups according to their thyroid-stimulating hormone (TSH) levels: well treated (TSH: 0.4-4 mIU/L), overtreated (TSH: <0.4 mIU/L), and undertreated (TSH: >4 mIU/L). The main outcomes were mortality and recurrent hospitalization within 3 months. Among 231 patients, 106 were euthyroid, 14 were overtreated, and 111 undertreated. Patients' mean age was 79.8 ± 9.4 years. In-hospital mortality occurred in 4.7% in euthyroid patients, 14.3% in the overtreated group, and 10.7% in the undertreated group (p = 0.183). Differences in 30-day (p = 0.287) and 90-day (p = 0.2) mortality or recurrent hospitalization (p = 0.438) were not significantly different as well. However, in patients who were markedly undertreated and overtreated (TSH: >10 mIU/L or below 0.4 mIU/L) compared with 0.4-10 mIU/L, a significant increase in 90-day mortality was observed (33.3% vs 15.1% p = 0.016). Treatment status was independently associated with 90-day mortality after controlling for confounders with an adjusted odds ratio of 3.55 (95% confidence interval: 1.39-9.06). Although mild under- or overtreatment of hypothyroidism does not have a significant detrimental effect on hospitalization outcomes of patients with acute decompensated HF, markedly under- and overtreatment are independently associated with rehospitalizations and 90-day mortality. Larger cohorts are needed to establish the relationship between treatment targets and hospitalization outcomes of patients at risk for HF hospitalization.

Insulin treatment of patients with gestational diabetes: does dosage play a role?

BACKGROUND AND OBJECTIVE: In nonpregnant patients high insulin requirements are associated with hypoglycemia and weight gain but not with improvement in glucose control. The effect of insulin requirement on maternal and neonatal outcomes in gestational diabetes mellitus (GDM) is yet unknown. METHODS: We conducted a retrospective cohort study of maternal and neonatal outcomes of pregnancy according to insulin requirements in women with GDM who were followed and delivered at the Yitzhak Shamir Medical Center between 2006 and 2016. The daily insulin dose in units per body weight was divided into quartiles and analyses were performed to compare the lowest, highest, and two middle quartiles. The primary outcome was a composite of any of the following: cesarean-section (CS), preeclampsia, macrosomia and large for gestational age (LGA) birth weight, neonatal intensive care unit admission, need for phototherapy, and neonatal hypoglycemia. RESULTS: Women were divided according to their insulin requirements as follows: 79 (24.8%) women who needed <0.13 IU/kg/day of insulin (insulin-sensitive group), 160 (50%) women who needed 0.14-0.42 IU/kg/day of insulin (comparison-group), and the rest who needed >0.43 IU/kg/day of insulin (insulin resistant group). There were no differences in the composite outcome between the groups (64.6, 61.3, and 69.6% for the insulin sensitive-, comparison- and resistant- groups, respectively, p = .44). Women in the insulin-resistant group had higher fasting glucose levels in the first trimester (91, 98 and 102 mg/dL for women in the insulin sensitive-, comparison- and insulin-resistant groups, respectively; p = .01). Women in the insulin-sensitive group had significantly better glycemic control (fasting glucose levels ≤90 mg/dL and 1-hour and 2-hour postprandial glucose levels ≤140 mg/dL and ≤120 mg/dL for more than 80% of measurements) than those in the insulin-resistant group (70.3 versus 29.9%; p < .001). The rate of CS was significantly higher in the insulin-resistant group (42.3 versus 24.1%; p = .03), but the rate of LGA birth weight was surprisingly higher in the insulin-sensitive group (29.5 versus 16.7%, p = .04). After controlling for confounders, women in the insulin-sensitive group had a decreased risk for CS in relation to the comparison group (OR = 0.46, 95%CI 0.23-0.9, p = .025). CONCLUSION: We found no association between insulin requirements and adverse composite outcome in women with GDM. However, those with higher insulin requirements have poorer glucose control and higher rates of CS than those with lower insulin requirements. Larger studies are needed to inquire short- and long-term outcomes of insulin requirements on fetal and maternal outcomes.

The risk of small and large for gestational age newborns in women with gestational diabetes according to pre-gestational body mass index and weight gain.

AIM: To explore the effects of pregestational body mass index (BMI) and gestational weight gain (GWG) on maternal and neonatal outcomes of women with gestational diabetes mellitus (GDM). METHODS: We conducted retrospective cohort analyses of outcomes among women with GDM who delivered at Shamir Medical Center, Israel (2017-2018). RESULTS: We included 673 women with GDM in our analysis, 217 (32.24%) with appropriate GWG (aGWG), 247 (36.7%) with excessive GWG (eGWG), and 209 (31%) with insufficient GWG (iGWG). Cesarean section (CS) was less prevalent among women with iGWG (19.6%), compared with women with eGWG (31.2%) and aGWG (31.1%) (p = .008). Small for gestational weight (SGA) newborns were more prevalent in women with iGWG 9.1%, compared with 2% and 0.9% for women with eGWG and aGWG, respectively (p<.001). Large for gestational age (LGA) newborns were significantly more prevalent in women with eGWG 17.4% compared with 4.8% and 9.7% in patients with iGWG and aGWG women, respectively (p<.001). SGA and LGA newborns were more prevalent in women with iGWG and e-GWG across all pre-gestational BMI groups >18.5 kg/m2. CONCLUSIONS: A complex interplay exists between pregestational weight, GWG, and GDM and pregnancy outcomes, specifically SGA and LGA newborns. A strict follow-up considering the pregestational BMI, GWG, blood glucose levels, treatment modality, and fetal abdominal circumference could assist in managing the complex interplay of patients with GDM for better neonatal outcomes.

Prediction of Personal Glycemic Responses to Food for Individuals With Type 1 Diabetes Through Integration of Clinical and Microbial Data.

OBJECTIVE: Despite technological advances, results from various clinical trials have repeatedly shown that many individuals with type 1 diabetes (T1D) do not achieve their glycemic goals. One of the major challenges in disease management is the administration of an accurate amount of insulin for each meal that will match the expected postprandial glycemic response (PPGR). The objective of this study was to develop a prediction model for PPGR in individuals with T1D. RESEARCH DESIGN AND METHODS: We recruited individuals with T1D who were using continuous glucose monitoring and continuous subcutaneous insulin infusion devices simultaneously to a prospective cohort and profiled them for 2 weeks. Participants were asked to report real-time dietary intake using a designated mobile app. We measured their PPGRs and devised machine learning algorithms for PPGR prediction, which integrate glucose measurements, insulin dosages, dietary habits, blood parameters, anthropometrics, exercise, and gut microbiota. Data of the PPGR of 900 healthy individuals to 41,371 meals were also integrated into the model. The performance of the models was evaluated with 10-fold cross validation. RESULTS: A total of 121 individuals with T1D, 75 adults and 46 children, were included in the study. PPGR to 6,377 meals was measured. Our PPGR prediction model substantially outperforms a baseline model with emulation of standard of care (correlation of R = 0.59 compared with R = 0.40 for predicted and observed PPGR respectively; P < 10-10). The model was robust across different subpopulations. Feature attribution analysis revealed that glucose levels at meal initiation, glucose trend 30 min prior to meal, meal carbohydrate content, and meal's carbohydrate-to-fat ratio were the most influential features for the model. CONCLUSIONS: Our model enables a more accurate prediction of PPGR and therefore may allow a better adjustment of the required insulin dosage for meals. It can be further implemented in closed loop systems and may lead to rationally designed nutritional interventions personally tailored for individuals with T1D on the basis of meals with expected low glycemic response.

The Gut Microbiome of Adults With Type 1 Diabetes and Its Association With the Host Glycemic Control.

OBJECTIVE: Previous studies have demonstrated an association between gut microbiota composition and type 1 diabetes (T1D) pathogenesis. However, little is known about the composition and function of the gut microbiome in adults with longstanding T1D or its association with host glycemic control. RESEARCH DESIGN AND METHODS: We performed a metagenomic analysis of the gut microbiome obtained from fecal samples of 74 adults with T1D, 14.6 ± 9.6 years following diagnosis, and compared their microbial composition and function to 296 age-matched healthy control subjects (1:4 ratio). We further analyzed the association between microbial taxa and indices of glycemic control derived from continuous glucose monitoring measurements and blood tests and constructed a prediction model that solely takes microbiome features as input to evaluate the discriminative power of microbial composition for distinguishing individuals with T1D from control subjects. RESULTS: Adults with T1D had a distinct microbial signature that separated them from control subjects when using prediction algorithms on held-out subjects (area under the receiver operating characteristic curve = 0.89 ± 0.03). Linear discriminant analysis showed several bacterial species with significantly higher scores in T1D, including Prevotella copri and Eubacterium siraeum, and species with higher scores in control subjects, including Firmicutes bacterium and Faecalibacterium prausnitzii (P < 0.05, false discovery rate corrected for all). On the functional level, several metabolic pathways were significantly lower in adults with T1D. Several bacterial taxa and metabolic pathways were associated with the host's glycemic control. CONCLUSIONS: We identified a distinct gut microbial signature in adults with longstanding T1D and associations between microbial taxa, metabolic pathways, and glycemic control indices. Additional mechanistic studies are needed to identify the role of these bacteria for potential therapeutic strategies.

Ovarian adrenal rest tumor in congenital adrenal hyperplasia: Is medical treatment the first line option?

Ovarian adrenal rest tumors (OARTs) are very rare. We describe a case of a young woman with uncontrolled classical congenital adrenal hyperplasia (CCAH), presenting with bilateral OARTs, successfully treated with steroid replacement. A 20-year-old woman, known to have 21OH-CCAH, presented with severe abdominal pain, vomiting, diarrhea, and fever. As a result of poor compliance, 6 months before her admission hirsutism worsened and amenorrhea, hyperpigmentation, and weakness developed. ACTH levels were 278 < pmol/L and 17OHP 91.3 nmol/L. She was admitted for parenteral antibiotics and high-dose hydrocortisone treatment. CT revealed bilateral juxta-ovarian masses (6.2 × 3.6 × 7.4 cm left and 5 × 2.2 × 3.2 cm right) that on MRI were iso-intense in T1 and hypointense in T2, with early enhancement and rapid washout. One week of high-dose hydrocortisone resulted in significant clinical and laboratory improvement and the patient was discharged with 2 mg dexamethasone/day. One month later US revealed shrinkage of the masses and dexamethasone dose was decreased. At three months from discharge, she has resumed regular menses, and a repeated MRI revealed the para-ovarian masses have shrunk. One year after the diagnosis, the para-ovarian masses have shrunk more to 2.8 × 1.9 × 4.3 on the left and 2.1 × 0.9 × 1.2 on the right with less contrast enhancement in comparison to previous test possibly due to fibrotic changes of the tissue. OARTs are rare tumors with a poorly known natural history, and surgery has been the first option in the few reported cases. We demonstrate that medical treatment is a good alternative, leading to significant tumor shrinkage over a short period.

Differentiated Thyroid Cancer with Biochemical Incomplete Response: Clinico-Pathological Characteristics and Long Term Disease Outcomes.

Although most patients with differentiated thyroid cancer (DTC) and biochemical incomplete response (BIR) follow a good clinical outcome, progression to structural disease may occur in 8-17% of patients. We aimed to identify factors that could predict the long-term outcomes of BIR patients. To this end, we conducted a retrospective review study of 1049 charts from our Differential Thyroid Cancer registry of patients who were initially treated with total thyroidectomy between 1962 and 2019. BIR was defined as suppressed thyroglobulin (Tg) > 1 ng/mL, stimulated Tg > 10 ng/mL or rising anti-Tg antibodies, who did not have structural evidence of disease, and who were assessed 12-24 months after initial treatment. We found 83 patients (7.9%) matching the definition of BIR. During a mean follow-up of 12 ± 6.6 years, 49 (59%) patients remained in a state of BIR or reverted to no evidence of disease, while 34 (41%) progressed to structural disease. At the last follow-up, three cases (3.6%) were recorded as disease-related death. The American Thyroid Association (ATA) Initial Risk Stratification system and/or AJCC/TNM (8th ed.) staging system at diagnosis predicted the shift from BIR to structural disease, irrespective of their postoperative Tg levels. We conclude that albeit 41% of BIR patients may shift to structural disease, and most have a rather indolent disease. Specific new individual data enable the Response to Therapy reclassification to become a dynamic system to allow for the better management of BIR patients in the long term.

Effect of Mini-invasive Floating Metatarsal Osteotomy on Plantar Pressure in Patients With Diabetic Plantar Metatarsal Head Ulcers.

BACKGROUND: Distal metatarsal osteotomy has been used to alleviate plantar pressure caused by anatomic deformities. This study's purpose was to examine the effect of minimally invasive floating metatarsal osteotomy on plantar pressure in patients with diabetic metatarsal head ulcers. METHODS: We performed a retrospective case series of prospectively collected data on 32 patients with diabetes complicated by plantar metatarsal head ulcers without ischemia. Peak plantar pressure and pressure time integrals were examined using the Tekscan MatScan prior to surgery and 6 months following minimally invasive floating metatarsal osteotomy. Patients were followed for complications for at least 1 year. RESULTS: Peak plantar pressure at the level of the osteotomized metatarsal head decreased from 338.1 to 225.4 kPa (P < .0001). The pressure time integral decreased from 82.4 to 65.0 kPa·s (P < .0001). All ulcers healed within a mean of 3.7 ± 4.2 weeks. There was 1 recurrence (under a hypertrophic callus of the osteotomy) during a median follow-up of 18.3 months (range, 12.2-27). Following surgery, adjacent sites showed increased plantar pressure and 4 patients developed transfer lesions (under an adjacent metatarsal head); all were managed successfully. There was 1 serious adverse event related to surgery (operative site infection) that resolved with antibiotics. CONCLUSION: This study showed that the minimally invasive floating metatarsal osteotomy successfully reduced local plantar pressure and that the method was safe and effective, both in treatment and prevention of recurrence. LEVEL OF EVIDENCE: Level III, retrospective case series of prospectively collected data.