Glycemic Control Among Adults With Type 1 Diabetes During Passover: A Pre-Post Single-center Study.

OBJECTIVES: No data are available regarding glycemic control of patients with type 1 diabetes (T1D) during Passover. Our aim in this study was to assess the effect of Passover on diabetes management and glycemic control in adult patients with T1D with nutritional changes during Passover (observant) compared with patients who did not change their dietary habits during Passover (nonobservant). METHODS: Observational pre-post study of adult patients with T1D, followed in a diabetes clinic in Israel. Data were downloaded from insulin pumps and continuous glucose monitoring for 37 days: 2 weeks before Passover; 9 days of Passover; and 2 weeks thereafter. Differences in percentage of time spent above target (>10.0 to >13.9 mmol/L), at target (3.9 to 10.0 mmol/L) and below target (<3.9 to <3.0 mmol/L), were compared using paired t tests or paired signed rank tests. RESULTS: The study cohort included 43 patients (23 observant, 20 nonobservant). The average blood glucose was significantly higher during Passover compared with the period before Passover---in nonobservant patients 8.2±1.5 mmol/L and 7.9±1.3 mmol/L (p=0.043), respectively, and in observant patients 8.7±1.6 mmol/L and 8.4±1.6 mmol/L (p=0.048), respectively. Time above range 10 to 13.9 mmol/L was increased in observant patients during Passover, as compared with the period before Passover, was 24.9±16.2% and 20.6±12.4% (p=0.04), respectively. The dose of bolus insulin had increased significantly in observant patients: 27.4±13.9 units during Passover, as compared with 24.2±11.2 units before Passover (p=0.02). CONCLUSIONS: Passover alters glycemic control and insulin needs in Jewish patients with T1D. It is advisable to make specific adjustments to maintain the recommended glycemic control.

Glucagon-like Peptide 1 Receptor Agonists and Cardiovascular Outcomes in Solid Organ Transplant Recipients With Diabetes Mellitus.

BACKGROUND: Glucagon-like peptide 1 receptor agonists (GLP1-RAs) reduce cardiovascular events and mortality in type 2 diabetes. Limited data are available on diabetes treatment after solid organ transplantation. We aimed to explore the effect of GLP1-RAs on cardiovascular outcomes in transplanted recipients with diabetes. METHODS: We extracted data on adult transplant recipients (kidney, lungs, liver, heart) insured in a large health maintenance organization. Death-censored patients with diabetes treated with GLP1-RAs were matched with nonusers. The primary outcome was a composite of major cardiovascular events (MACEs): a nonfatal cardiac event (myocardial infarction, stable/unstable angina, coronary bypass, and coronary angiography), ischemic stroke and all-cause mortality. Secondary outcomes were MACE or peripheral vascular disease (MACE-PVD), and all-cause mortality. Safety outcomes included biliopancreatic adverse events. RESULTS: We included 318 patients (69% males, average age 58.3 ±â€…11.0 y) with a 3.1-y median follow-up. The incidence of MACE was 101 of 1000 patient-years in GLP1-RAs users compared with 134 of 1000 in controls (hazard ratio [HR] 0.46; 95% confidence interval [CI], 0.27-0.78). GLP1-RAs similarly reduced the risk of MACE-PVD (HR 0.53; 95% CI, 0.33-0.88) and the risk of all-cause mortality (HR 0.39; 95% CI, 0.18-0.84). Biliopancreatic adverse events occurred less in GLP1-RA users. CONCLUSIONS: Transplant recipients with diabetes who used GLP1-RAs had lower risks for MACE and all-cause mortality. These results may profoundly implicate the daily management of posttransplant recipients with diabetes, a population with a high prevalence of cardiometabolic risk factors and cardiovascular death. Transplant patients are usually excluded from randomized controlled trials and, hence might be undertreated with disease-modifying drugs. Larger prospective studies are needed in this unique population.

Clarifying the relationship between mental illness and recidivism using machine learning: A retrospective study.

OBJECTIVE: There is currently inconclusive evidence regarding the relationship between recidivism and mental illness. This retrospective study aimed to use rigorous machine learning methods to understand the unique predictive utility of mental illness for recidivism in a general population (i.e.; not only those with mental illness) prison sample in the United States. METHOD: Participants were adult men (n = 322) and women (n = 72) who were recruited from three prisons in the Midwest region of the United States. Three model comparisons using Bayesian correlated t-tests were conducted to understand the incremental predictive utility of mental illness, substance use, and crime and demographic variables for recidivism prediction. Three classification statistical algorithms were considered while evaluating model configurations for the t-tests: elastic net logistic regression (GLMnet), k-nearest neighbors (KNN), and random forests (RF). RESULTS: Rates of substance use disorders were particularly high in our sample (86.29%). Mental illness variables and substance use variables did not add predictive utility for recidivism prediction over and above crime and demographic variables. Exploratory analyses comparing the crime and demographic, substance use, and mental illness feature sets to null models found that only the crime and demographics model had an increased likelihood of improving recidivism prediction accuracy. CONCLUSIONS: Despite not finding a direct relationship between mental illness and recidivism, treatment of mental illness in incarcerated populations is still essential due to the high rates of mental illnesses, the legal imperative, the possibility of decreasing institutional disciplinary burden, the opportunity to increase the effectiveness of rehabilitation programs in prison, and the potential to improve meaningful outcomes beyond recidivism following release.

Drug-Drug Interactions Between Glucagon-Like Peptide 1 Receptor Agonists and Oral Medications: A Systematic Review.

BACKGROUND: Glucagon-like peptide 1 receptor agonists (GLP1RAs) are used in the treatment of diabetes and obesity. Their slowing effect of gastric emptying might change oral drug absorption, potentially affecting pharmacokinetics, particularly in the case of medications with a narrow therapeutic index. PURPOSE: The purpose of this systematic review is to summarize data on drug-drug interactions between GLP1RAs and oral drugs. DATA SOURCES: The PubMed and EMBASE databases were searched up to November, 1st 2023. STUDY SELECTION: We selected pharmacokinetic studies of any injectable GLP1RA given with an oral medication, and product prescribing sheets reporting data without access to the original study. DATA EXTRACTION: Two authors independently extracted the data. DATA SYNTHESIS: Twenty-two reports and six prescribing sheets were included. Treatment with GLP1RAs resulted in unaffected or reduced Cmax and delayed tmax of drugs with high solubility and permeability (warfarin, contraceptive pills, acetaminophen), drugs with high solubility and low permeability (angiotensin converting enzyme inhibitors), drugs with low solubility and high permeability (statins) and drugs with low solubility and permeability (digoxin). However, the use of GLP1RAs did not exert clinically significant changes in the AUC or differences in clinically relevant endpoints. LIMITATIONS: The major limitations of the studies that are included in this systematic review are the enrollment of healthy subjects and insufficient data in conditions that might affect pharmacokinetics (e.g., kidney dysfunction). CONCLUSIONS: To conclude, reduced Cmax and delayed tmax of drugs co-administered with GLP1RAs are consistent with the known delayed gastric output by the latter. Nevertheless, the overall drug exposure was not considered clinically significant. Dose adjustments are probably not required for simultaneous use of GLP1RAs with oral medications. Still, results should be carefully generalized to cases of background kidney dysfunction or when using drugs with narrow therapeutic index. The study is registered in PROSPERO: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022332339 .

The Association Between Hypothyroidism Treatment and Mortality in Patients Hospitalized in Surgical Wards.

Limited data are available regarding the association between pre-admission thyroid-stimulating hormone (TSH) levels and prognosis in hospitalized surgical patients treated for hypothyroidism. We retrospectively evaluated a cohort of 1,451 levothyroxine-treated patients, hospitalized to general surgery wards. The 30-day mortality risk was 2-fold higher for patients with TSH of 5.0-10.0 mIU/L (adjusted OR, 2.3; 95% CI 1.1-5.1), and 3-fold higher for those with TSH > 10.0 mIU/L (3.4; 95% CI 1.3-8.7). Long-term mortality risk was higher in patients with TSH of 5.0-10.0 and above 10.0 mIU/L (adjusted HR, 1.2; 95% CI, 1.0-1.6, and 1.7; 95% CI 1.2-2.4, respectively). We found that in levothyroxine-treated adults hospitalized to surgical wards, increased pre-admission TSH levels are associated with increased short- and long-term mortality.

A combined cell and growth factor delivery for the repair of a critical size tibia defect using biodegradable hydrogel implants.

The ability to repair critical-sized long-bone injuries using growth factor and cell delivery was investigated using hydrogel biomaterials. Physiological doses of the recombinant human bone morphogenic protein-2 (rhBMP2) were delivered in a sustained manner from a biodegradable hydrogel containing peripheral human blood-derived endothelial progenitor cells (hEPCs). The biodegradable implants made from polyethylene glycol (PEG) and denatured fibrinogen (PEG-fibrinogen, PF) were loaded with 7.7 µg/ml of rhBMP2 and 2.5 × 106 cells/ml hEPCs. The safety and efficacy of the implant were tested in a rodent model of a critical-size long-bone defect. The hydrogel implants were formed ex-situ and placed into defects in the tibia of athymic nude rats and analyzed for bone repair after 13 weeks following surgery. The hydrogels containing a combination of 7.7 µg/ml of rhBMP2 and 2.5 × 106 cells/ml hEPCs were compared to control hydrogels containing 7.7 µg/ml of rhBMP2 only, 2.5 × 106 cells/ml hEPCs only, or bare hydrogels. Assessments of bone repair include histological analysis, bone formation at the site of implantation using quantitative microCT, and assessment of implant degradation. New bone formation was detected in all treated animals, with the highest amounts found in the treatments that included animals that combined the PF implant with rhBMP2. Moreover, statistically significant increases in the tissue mineral density (TMD), trabecular number and trabecular thickness were observed in defects treated with rhBMP2 compared to non-rhBMP2 defects. New bone formation was significantly higher in the hEPC-treated defects compared to bare hydrogel defects, but there were no significant differences in new bone formation, trabecular number, trabecular thickness or TMD at 13 weeks when comparing the rhBMP2 + hEPCs-treated defects to rhBMP2-treated defects. The study concludes that the bone regeneration using hydrogel implants containing hEPCs are overshadowed by enhanced osteogenesis associated with sustained delivery of rhBMP2.

Rapamycin prevents the long-term impairing effects of adolescence Δ-9-tetrahydrocannabinol on memory and plasticity in male rats.

Long-lasting cognitive impairment is one of the most central negative consequences related to the exposure to cannabis during adolescence and particularly of Δ-9-tetrahydrocannabinol (THC). The aim of this study was to compare the protracted effects of adolescent versus late-adolescent chronic exposure to THC on short-term memory and plasticity and to examine whether rapamycin, a blocker of the mammalian target of rapamycin (mTOR) pathway, can restore THC-induced deficits in memory and plasticity. Male rats were injected with ascending doses of THC [2.5, 5, 10 mg/kg; intraperitoneally (i.p.)] during adolescence and late-adolescence (post-natal days 30-41 and 45-56, respectively), followed by daily injections of rapamycin (1 mg/kg, i.p.) during the first 10 days of cessation from THC. Thirty days after the last injection, rats were tested for short-term and working memory, anxiety-like behaviour, and plasticity in the pathways projecting from the ventral subiculum (vSub) of the hippocampus to the prefrontal cortex (PFC) and nucleus accumbens (NAc). THC exposure in adolescence, but not late-adolescence, was found to induce long-term deficits in object recognition short-term memory and synaptic plasticity in the hippocampal-accumbens pathway. Importantly, rapamycin rescued these persistent effects of THC administered during adolescence. Our findings show that some forms of memory and plasticity are sensitive to chronic THC administration during adolescence and that rapamycin administered during THC cessation may restore cognitive function and plasticity, thus potentially protecting against the possible long-term harmful effects of THC.

Abnormal Brain Bioenergetics in First-Episode Psychosis.

BACKGROUND: Converging evidence indicates impaired brain energy metabolism in schizophrenia and other psychotic disorders. Creatine kinase (CK) is pivotal in providing adenosine triphosphate in the cell and maintaining its levels when energy demand is increased. However, the activity of CK has not been investigated in patients with first-episode schizophrenia spectrum disorders. METHODS: Using in vivo phosphorus magnetization transfer spectroscopy, we measured CK first-order forward rate constant (k f ) in the frontal lobe, in patients with first-episode psychosis (FEP; n = 16) and healthy controls (n = 34), at rest. RESULTS: CK k f was significantly reduced in FEP compared to healthy controls. There were no differences in other energy metabolism-related measures, including phosphocreatine (PCr) or ATP, between groups. We also found increase in glycerol-3-phosphorylcholine, a putative membrane breakdown product, in patients. CONCLUSIONS: The results of this study indicate that brain bioenergetic abnormalities are already present early in the course of schizophrenia spectrum disorders. Future research is needed to identify the relationship of reduced CK k f with psychotic symptoms and to test treatment alternatives targeting this pathway. Increased glycerol-3-phosphorylcholine is consistent with earlier studies in medication-naïve patients and later studies in first-episode schizophrenia, and suggest enhanced synaptic pruning.

Denosumab-associated hypocalcemia: Does gender play a role?

OBJECTIVE: It is well recognized that the presentation, treatment, and outcomes of various diseases may differ between men and women. We recently reported a 7.4% rate of denosumab-associated hypocalcemia in community-dwelling osteoporotic patients. This study sought to investigate the role of gender in this complication. STUDY DESIGN: Retrospective community-dwelling cohort. METHOD: The databases of a large health maintenance organization were searched for adult patients treated with denosumab for osteoporosis in 2010-2018. Rates and predictors of denosumab-associated hypocalcemia (serum calcium ≤8.5 mg/mL) were analyzed by gender. RESULTS: The cohort included 1871 women and 134 men. Compared with the women, the men were characterized by older median age (81 vs. 77 years, p = 0.005), higher likelihood to receive denosumab as a first-line treatment (22% vs. 6%, p < 0.001), less treatment with calcium supplements (42% vs. 53%, p = 0.012), and lower median eGFR level (66.1 vs. 79.8 mL/min/1.73m2, p < 0.001). Denosumab-associated hypocalcemia developed in 133 women (7.1%) and 16 men (11.9%) (p = 0.04); the drug was discontinued in 75% and 61%, respectively. The strongest predictors of hypocalcemia in women were levels of pretreatment albumin-adjusted serum calcium (OR 0.08, 95% CI (0.04, 0.14)) and creatinine (OR 2.43, 95% CI (1.45, 4.05)). There were no predictors in men. On propensity matching of 126 men and 126 women, gender was not a predictor of hypocalcemia. CONCLUSION: Denosumab-treated men were significantly older than treated women and had a lower eGFR and more advanced osteoporosis. These findings suggest that selection bias rather than male genderper se underlies the higher rate of denosumab-associated hypocalcemia in men.

White Matter Measures and Cognition in Schizophrenia.

White matter (WM) abnormalities are commonly reported in schizophrenia but whether these arise from the axon or myelin compartments or both is not known. In addition, the relationship between WM abnormalities and cognitive function is not fully explored in this condition. We recruited 39 individuals with schizophrenia spectrum disorders and 37 healthy comparison subjects. All participants underwent MRI scanning at 4 Tesla to collect data in the prefrontal white matter on magnetization transfer ratio (MTR) and diffusion tensor spectroscopy (DTS) which provide information on myelin and axon compartments, respectively. We also collected Matrics Composite Cognitive Battery (MCCB) and Stroop cognitive data. We found an elevated N-acetylaspartate (NAA) apparent diffusion coefficient in schizophrenia in this cohort as in our previous work; we also observed poorer performance on both the MCCB composite and the Stroop in schizophrenia patients compared to controls. The MTR measure was correlated with the MCCB composite (r = 0.363, p = 0.032) and Stroop scores (r = 0.387, p = 0.029) in healthy individuals but not in schizophrenia. Since this is the first exploration of the relationship between these WM and cognitive measures, we consider our analyses exploratory and did not adjust for multiple comparisons; the findings are not statistically significant if adjusted for multiple comparisons. These findings indicate that WM integrity is associated with cognitive function in healthy individuals but this relationship breaks down in patients with schizophrenia.

Mental Health Units in Correctional Facilities in the United States.

BACKGROUND: The prevalence of severe mental illness (SMI) in correctional settings is alarmingly high. Some correctional facilities have developed mental health units (MHUs) to treat incarcerated individuals with SMI. OBJECTIVE: To identify existing MHUs in the United States and collate information on these units. DATA SOURCES: A systematic review using Criminal Justice Abstracts, ERIC, PsycINFO, PubMed, and SocINDEX, plus an exploratory review using the Google search engine were conducted. MHUs were included if they were located within an adult correctional facility in the United States, specifically catered to SMI populations, and were in active operation as of June 2019. RESULTS: Eleven articles were identified through the peer-reviewed literature, but there were still major gaps in the information on MHUs. The Google search identified 317 MHUs. The majority of units were located within prisons (79.5%) and served only men (76%). The Google search found information indicating that 169 (53.3%) offered groups or programming to inmates; 104 (32.8%) offered individual therapy; and 89 (23%) offered both. One hundred sixty-six units (52.4%) had dedicated mental health staff, and 75 (23.7%) provided mental health training to correctional officers. Information on funding and outcomes of the MHUs is presented. LIMITATIONS: Use of the Google search engine and sources that have not been peer reviewed limits the robustness of conclusions about the MHUs. CONCLUSIONS: Standards for developing and implementing MHUs are not widespread. The shortcomings of current MHUs are discussed in the context of desired criteria for size, staffing, and programming.

Hyperparathyroidism in patients over 75: Clinical characteristics and outcome. Is conservative treatment a safe alternative?

OBJECTIVE: With the current aging of the world's population, primary hyperparathyroidism (PHPT) is increasingly detected in the elderly. Yet data on the presentation and outcome of PHPT in this group are scarce. The objective was to describe a cohort of patients aged 75 years or more with PHPT observed in our endocrine clinic. STUDY DESIGN: A retrospective analysis of medical records in an endocrine clinic at a tertiary hospital. We evaluated 182 patients with PHPT, aged 75 years or more at their last follow-up, all diagnosed at age 65 or more. Laboratory data were compared at diagnosis and last follow-up. RESULTS: Mean age at diagnosis was 73 ± 4 years, last follow-up was at 83 ± 4 years, and mean follow-up was 11.3 ± 5.5 years. Osteoporosis, fractures, and nephrolithiasis were diagnosed in 114(63 %), 84(46 %), and 43(24 %) patients, respectively. Overall, 150 patients had an indication for surgery; of them, the 29 who underwent parathyroidectomy were younger than the non-operated patients and had higher rates of hypercalciuria. During the follow-up of the 141 patients who did not undergo operation, serum and urinary calcium levels significantly had decreased, and vitamin D level had increased at last visit (10.4 ± 0.5 mg/dl, 161 ± 70 mg/24 h, 69 ± 17 nmol/l, p < 0.01 respectively) compared with levels at diagnosis (10.6 ± 0.2 mg/dl, 223 ± 95 mg/24 h, 53 ± 15 nmol/l, respectively, p = 0.001). Overall, 38 of the 182 patients (20 %) died during follow-up; these patients were significantly older at diagnosis (76 ± 5 vs. 72 ± 4 years) but there were no differences in laboratory variables. CONCLUSIONS: While most patients had a formal indication for surgery, few underwent parathyroidectomy. Serum and urinary calcium significantly decreased during follow-up in patients who did not undergo surgery. Our data are reassuring and support at least the consideration of conservative treatment for these patients.

Cognitive and clinical predictors of community functioning across the psychoses.

Schizophrenia, bipolar disorder, and related psychotic illnesses are common, serious mental disorders that are often associated with functional impairments and poor quality of life, even after clinical recovery. Cognitive dysfunction is a strong predictor of functional impairment; however, findings regarding relative impairments in functioning and cognition across diagnoses have been mixed, as have reports of the contribution of clinical symptoms and other illness features to functioning across diagnostic boundaries. We assessed 211 patients with psychotic disorders and 87 healthy controls using the MATRICS Consensus Cognitive Battery, clinical measures of state mood and psychotic symptoms, and an interview measure of community functioning. Diagnostic groups were compared on MATRICS composite and domain scores, and clinical and functional measures. We then examined cognitive, clinical, and demographic predictors of community functioning using stepwise hierarchical linear regression. All three patient groups exhibited deficits in most cognitive domains relative to controls, and significantly poorer community functioning. While scores on most cognitive domains did not differ by diagnosis, when groups did differ patients with schizophrenia performed worse than patients with bipolar disorder. Cognition was correlated with functioning across the sample. The final regression model included negative symptoms, mania, social cognition, and processing speed, and explained 47% of the variance in community functioning scores across patient groups. Residual negative symptoms, residual mania, and social cognition significantly and independently predicted community functioning. These findings indicate that, while all cognitive domains are associated with community outcomes, when considered together and with clinical symptoms, negative symptoms, mania, and social cognition are the strongest predictors across diagnoses. Development of interventions targeting negative symptoms and social cognition may be effective in improving community functioning for patients across diagnoses.

Detecting Recurrence Following Lobectomy for Thyroid Cancer: Role of Thyroglobulin and Thyroglobulin Antibodies.

BACKGROUND: The use of thyroglobulin (Tg) and thyroglobulin antibodies (TgAb) for detecting disease recurrence is well validated following total thyroidectomy and radioiodine ablation. However, limited data are available for patients treated with thyroid lobectomy. METHODS: Patients who had lobectomy for papillary thyroid cancer followed for >1 year, with sufficient data on Tg and TgAb, including subgroup analysis for Hashimoto's thyroiditis and contralateral nodules. RESULTS: One-hundred sixty-seven patients met the inclusion criteria. Average tumor size was 9.5 ±â€…6 mm. Following lobectomy, Tg was 12.1 ±â€…14.8 ng/mL. Of 52 patients with Hashimoto's thyroiditis, 38% had positive TgAb with titers of 438 ±â€…528 IU/mL, and in patients without TgAb the mean Tg level was 14.7 ±â€…19.0 ng/mL. In 34 patients with contralateral nodules ≥1 cm, Tg was 15.3 ±â€…17 ng/mL. During the first 2 years of follow-up, Tg declined ≥1 ng/mL in 42% of patients (by 5.1 ±â€…3.7 ng/mL), remained stable in 22%, and increased in 36% (by 4.9 ±â€…5.7 ng/mL). During a mean follow-up of 6.5 years (78 ±â€…43.5 months), 18 patients had completion thyroidectomy and 12 were diagnosed with contralateral cancer (n = 8) or lymph node metastases (n = 4). In patients with recurrence followed for >2 years, there was a rise in Tg in 3 cases, Tg was stable in 2 cases, and in 1 TgAb decreased from 1534 to 276 IU/mL despite metastatic lymph nodes. Basal Tg and Tg dynamics did not predict disease recurrence. CONCLUSIONS: Serum thyroglobulin used independently is of limited value for predicting or detecting disease recurrence following thyroid lobectomy. Other potential roles of Tg, such as detecting distant metastases following lobectomy, should be further studied.

Risk for Infections During Treatment With Denosumab for Osteoporosis: A Systematic Review and Meta-analysis.

CONTEXT: Denosumab inhibits the receptor activator of nuclear factor κ-Β ligand, an immune system modulator. Safety endpoints including risk for infections were assessed as secondary outcomes in randomized controlled trials (RCTs) of the drug. OBJECTIVE: To assess the risk of serious adverse events of infections (SAEI) in denosumab-treated patients. DATA SOURCES: PubMed and Cochrane Central Register of Controlled Trials were searched up to May 27, 2019. STUDY SELECTION: All RCTs of denosumab (60 mg every 6 months) versus any comparator were included. We excluded trials in cancer patients for prevention of skeletal-related events. DATA EXTRACTION: Two reviewers independently applied selection criteria and extracted the data. Risk ratios (RR) with 95% confidence intervals (CI) were pooled using a fixed effect model. Sensitivity analysis was based on risk of bias. DATA SYNTHESIS: Thirty-three studies (22 253 patients) were included. There was a higher incidence of SAEI during denosumab treatment versus any comparator (RR, 1.21; 95% CI, 1.04-1.40; I2 = 0%), mainly of ear, nose, and throat (RR, 2.66; 95% CI, 1.20-5.91) and gastrointestinal origin (RR, 1.43; 95% CI, 1.02-2.01). RR was similar in a sensitivity analysis based on adequate allocation concealment. The RR of any infection (RR, 1.03; 95% CI, 0.99-1.06) and infection-related mortality (RR, 0.50; 95% CI, 0.20-1.23) was comparable between groups. CONCLUSIONS: A higher incidence of SAEI is demonstrated during treatment with denosumab in an osteoporosis dose. Nevertheless, the overall risk for any infection or related mortality is similar to comparator groups. These findings merit consideration before therapy initiation.

Response to Therapy Assessment in Intermediate-Risk Thyroid Cancer Patients: Is Thyroglobulin Stimulation Required?

Introduction: The 2015 American Thyroid Association (ATA) guidelines recommend response to therapy (RTT) assessment 1-2 years after initial treatment in differentiated thyroid cancer (DTC) patients to guide thyrotropin (TSH) goals and long-term follow-up. We hypothesized that data collected during the first 2 years of follow-up may be sufficient to determine RTT without thyroglobulin (Tg) stimulation. Materials and Methods: Patients treated with total thyroidectomy and radioiodine for intermediate-risk DTC, followed for >2 years, and had sufficient follow-up data were included. Data on Tg, ultrasound, scans, and long-term outcomes were collected. Results: One-hundred twenty patients met inclusion criteria, with 68% women and mean age 55 ± 15 years. Intermediate risk was due to lymph-node involvement (72%), extrathyroidal extension (51%), vascular invasion (12%), and high-risk histology (9%). At the end of follow-up of 7 ± 4 years, 26% had persistent disease (14% biochemical, 12% structural). According to the ATA RTT system (using stimulated-Tg), 56% had excellent RTT, of whom only 2% had disease at the end of follow-up. In the "nonstimulated" system (which includes basal Tg, post-131I therapy whole-body scan (TxWBS) for assessment of residual lymph-node metastases after surgery, and structural imaging studies), 57% had excellent response, of whom none had disease at the end of follow-up. Only eight patients (7%) were classified differently due to recombinant human thyrotropin stimulation (as either excellent or indeterminate response), with no difference in predictive value, with a receiver-operator characteristic area under the curve of 0.903 with Tg-stimulation and of 0.918 without. Conclusions: In patients with no evidence of disease during the first 2 years of follow-up, the addition of stimulated-Tg adds little prognostic information. We suggest the use of excellent RTT based on basal Tg together with TxWBS and structural imaging studies.

Endothelial Progenitor Cells inhibit jaw osteonecrosis in a rat model: A major adverse effect of bisphosphonate therapy.

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse effect of antiresorptive and antiangiogenic therapies. MRONJ is identified by chronic wounds in the oral mucosa associated with exposed necrotic bone. We hypothesized that zoledronic acid (ZOL) impairs keratinocyte and fibroblast function and reduces soft tissue vascularization; therefore, treating MRONJ with proangiogenic cells may benefit MRONJ patients. The effect of ZOL and dexamethasone (DEX) on gingival fibroblasts and keratinocytes was investigated. In-vitro, ZOL inhibited fibroblast and keratinocyte proliferation, delaying scratch healing. In-vivo, exposed bone was detected at tooth extraction sites, mainly in ZOL(+)/DEX(+) rats; and was associated with significantly decreased soft tissue vascularization, serum-VEGF, and tissue-VEGF. Local injection of early and late endothelial progenitor cells (EPCs) healed 13 of 14 MRONJ lesions compared with 2/7 lesions in the mesenchymal stem cells, and 2/6, in culture-medium group. The EPCs reduced necrotic bone area, increased serum and tissue VEGF levels. EPCs engraftment was minimal, suggesting their paracrine role in MRONJ healing. The EPC-conditioned medium improved scratch healing of keratinocytes and fibroblasts via VEGF pathway and elevated mRNA of VEGFA and collagen1A1. In conclusion, a novel MRONJ treatment with EPCs, increased vascularization and improved epithelial and fibroblast functions as well as cured the lesion.

Bone-Marrow Suppression in Elderly Patients Following Empiric Radioiodine Therapy: Real-Life Data.

Background: Elderly patients with differentiated thyroid cancer (DTC) tend to have more advanced disease at presentation, for which high activities of radioiodine (RAI) are often recommended. However, the 2015 American Thyroid Association guidelines recommend that empirically administered activities of RAI >150 mCi should be avoided in patients >70 years of age, based on calculated bone-marrow exposure according to two dosimetry-based studies. This study aimed to evaluate the effect of RAI treatment on bone-marrow function in elderly DTC patients. Methods: DTC patients ≥70 years of age who received RAI treatment and on whom a complete blood count was performed before and after treatment were included. Blood counts within one year before RAI and one year following treatment were compared in order to assess for marrow suppression. The impact of demographic, clinical, and laboratory variables on complete blood count were assessed. Results: One hundred fifty-three treatments in 122 patients met inclusion criteria, with a mean patient age of 76 ± 4.3 years, and 75% were women. High-risk features at presentation included T4 disease in 17%, lymph node metastases in 34%, and distant metastases in 14%. Mean RAI activity was 136.8 ± 48 mCi (82% ≥ 100 mCi, 66% ≥ 150 mCi). Of 153 RAI treatments analyzed, 114 (74%) were first treatments, 28 (18%) second treatments, seven (5%) third treatments, and four (3%) fourth treatments. At 0-3 months after RAI treatment, there was a statistically significant decrease in platelets (238 ± 66 vs. 216 ± 69 × 109/L, 10% decrease; p < 0.001), white blood cells (WBC; 6.9 ± 2 vs. 6.1 ± 1.9 × 109/L, 13% decrease; p < 0.001), and hemoglobin (Hb) in women (12.8 ± 1.1 vs. 12.4 ± 1.1 g/dL, 3% decrease; p = 0.01). Mean platelets, WBC, Hb in women, and lymphocytes remained decreased (but within the reference range) one year after treatment. Subgroup analysis demonstrated platelet suppression only with activities ≥100 mCi, and WBC and Hb suppression only with activities ≥150 mCi, with mean values within the reference ranges. There were no clinically significant cytopenia events during follow-up. Conclusions: Empiric RAI treatment in elderly patients causes mild bone-marrow suppression, with little clinical significance. Activities of 150-200 mCi can be safely used when indicated.