The Presence of Anti-TPO Antibodies Increase the Likelihood of Post-I131 Hypothyroidism.

The use of radioactive iodine in the treatment of hyperthyroidism is common practice. However, a standardized treatment protocol with regard to radioactive iodine treatment (RAI) remains subject to discussion. We retrospectively analyzed 100 patient records. Patient diagnosis, age, gender, body mass index (BMI), dose of radioactive iodine, thyroid size, the 24 h radioiodine uptake (24 h RAIU) and protein bound iodine (PBI) were deducted, as well as the use of antithyroid drugs prior to RAI. Biochemical parameters were obtained, such as TSH, fT4, fT3, Anti-TPO, Anti-TG antibodies and thyroid stimulating antibodies. After 5 years of follow-up, 46% of the patients proved to be hypothyroid, whereas 8% of the patients were not cured after one dose of RAI. One year after RAI, a larger proportion of patients with a toxic nodule developed hypothyroidism compared to patients with a multinodular goiter (MNG) (44.2% vs. 21.2%). Radioactive iodine dose, PBI, RAIU, BMI, size of the thyroid gland, diagnosis, age and TPO-antibodies showed statistically significant differences in the development of hypothyroidism. Furthermore, thiamazole pretherapy was shown to be a predictor of hypothyroidism, as well as a high PBI value, exhibiting a positive predictive value of 85.2% when the PBI exceeded 0.16. We suggest a standardized measurement of TPO-Ab's to further determine their role in the development of hypothyroidism after RAI. The empirical dosing regimen was very effective, illustrating a 92% cure rate after 1 dose.

Respiratory Muscle Strength Is Related to Handgrip Performance in Community-Dwelling Persons Aged 80+ from the BUTTERFLY Study.

INTRODUCTION: This study aimed to evaluate the association of respiratory muscle strength with sarcopenia and its indicators in the oldest old. METHODS: Maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), and sarcopenia-related factors (handgrip strength and appendicular lean mass) were evaluated in a cohort of n = 286 (45.5% female) non-frail, community-dwelling persons aged 83.6 ± 3.0 years (age range 80-97 years). RESULTS: The sample presented a sarcopenia prevalence of 32.2%. Sarcopenic subjects showed comparable MIP and MEP as non-sarcopenic ones (female: MIP 43.9 ± 18.9 vs. 50.3 ± 19.5, p = 0.053; MEP 63.0 ± 23.0 vs. 69.2 ± 19.1, p = 0.067; male: MIP, 65.1 ± 24.4 vs. 64.4 ± 23.9, p = 0.433; MEP 87.7 ± 33.3 vs. 93.8 ± 30.9, p = 0.124). Statistically significant but very low associations were found between grip strength and MIP (r = 0.193 for male, p < 0.05 and r = 0.257 for female participants, p < 0.01) and MEP (r = 0.200 for male, p < 0.01 and r = 0.191 for female participants, p < 0.05). Lean mass was significantly correlated to MIP and MEP in female (r = 0.253, p < 0.01 and r = 0.343, p < 0.01, respectively), whereas this association was not found in male participants. Grip strength was the only statistically significant predictor of MEP (r2 = 0.212, p < 0.001), while MIP was independently predicted by age, male sex, and grip strength (r2 = 0.177, p < 0.001). CONCLUSIONS: Peripheral muscle strength is a statistically significant, albeit weak predictor for respiratory muscle strength in well-functioning, community-dwelling persons aged 80+. When confronted to a low grip strength, one should be aware of concomitant respiratory muscle weakness, as this is a known risk factor for atelectasis and pneumonia. Given the relatively low association with handgrip strength, respiratory muscle strength testing might be indicated.

Immunosuppressive therapy management in cancer patients with autoimmune diseases treated with immune checkpoint inhibitors: A case series and systematic literature review.

INTRODUCTION: Prescribing immune checkpoint inhibitors (ICIs) to cancer patients with an autoimmune disease (AID) is presumed safe when cautious adverse event management is applied. However, guidelines on immunosuppressant (IS) adaptations are limited and real-world evidence is scarce. METHODS: Current practice of IS adaptations is described in a case series of AID patients treated with ICIs in a tertiary university hospital in Belgium (1/1/2016-31/12/2021). Patient, drug and disease-related data were documented using retrospective chart review. A systematic search of the PubMed database was performed to identify similar cases (1/1/2010-30/11/2022). RESULTS: Sixteen patients were described in the case series (62% with active AID). Systemic IS were changed before ICI initiation in 5/9 patients. Four patients continued therapy, of which one achieved partial remission. Patients who had IS (partially) stopped before ICI start (n = 4) had AID flares in two cases; immune-related adverse events in three cases. In the systematic review, 37 cases were identified in 9 articles. Corticosteroids (n = 12) and non-selective IS (n = 27) were continued in, respectively, 66% and 68% of patients. Methotrexate was frequently discontinued (13/21). Biologicals, excluding tocilizumab and vedolizumab, were withheld during ICI treatment. Out of all patients with flares (n = 15), 47% had stopped IS therapy before ICI start and 53% had continued their AID drugs. CONCLUSIONS: A detailed overview of IS management in patients with AID receiving ICI therapy is presented. Expanding the knowledge base germane to IS management with ICI therapy in the diverse population is essential to evaluate their mutual impact, thus advancing responsible patient care.

Impact of COVID-19 on Physical Activity, Fatigue, and Frailty in Community-Dwelling Older Adults: A Cross-Sectional Study.

This study aimed to describe the level of physical activity and its relation to fatigue and frailty during the COVID-19 pandemic in community-dwelling older adults aged 80 years and over. Three hundred and ninety-one older adults (aged 86.5 ± 3.00) completed a survey including physical activity, the Mobility Tiredness scale, and the FRAIL scale. Linear regression analysis was conducted to assess whether the variables age, sex, and physical activity (independent factors) were significantly related to fatigue and frailty. Respectively, 30.5% and 24.7% of the participants reported a decrease in walking and in energy-intensive activities; 25.4% reported increased sedentary behavior. A lower level of physical activity was associated with higher levels of fatigue and increased frailty risk (p < .05), independently from psychological symptoms. These results are important because participants with lower levels of physical activity and more sedentary behavior are more likely to feel fatigued and have higher risk to be frail.

Durvalumab-induced thyroiditis in a patient with non-small cell lung carcinoma: a case report and review of pathogenic mechanisms.

BACKGROUND: Immune checkpoint inhibitors (ICI) targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 and its ligand (PD-1/PD-L1) have become the current standard-of-care for advanced cancers. This novel therapeutic approach comes with its costs in the form of immune-related adverse events (irAE), including endocrinopathy. CASE PRESENTATION: A 63-year-old woman was diagnosed with a non-small cell lung carcinoma of the right superior lobe, cT3N2M0. She developed thyrotoxicosis followed by hypothyroidism induced by consolidation immunotherapy with durvalumab (anti-PD-L1). Analysis of the human leukocyte antigen (HLA) region showed HLA-DR4 (susceptible) and DR13 (protective). The possible mechanisms are subsequently discussed in detail. CONCLUSIONS: The case of a patient with thyroiditis associated with the PD-L1 inhibitor durvalumab is described, highlighting the need for proactive monitoring of thyroid hormone levels. Identifying biomarkers associated with an increased risk of ICI-induced side effects (such as HLA) is of interest for better patient selection, optimal management and improved understanding of the mechanisms involved.

Value of [11C]-Methionine PET/CT in Preoperative Localization of Parathyroid Adenomas.

There are multiple imaging modalities in primary hyperparathyroidism. Ultrasound examination and subtraction scintigraphy are usually the first-line imaging techniques. When these results are negative or inconsistent, additional [11C]-methionine PET/CT (MET-PET/CT) or 4-dimensional computed tomography can be performed. ​This study aims to evaluate MET-PET/CT in comparison with other imaging techniques in primary hyperparathyroidism. This is a retrospective cohort study. Eighty-four patients with primary hyperparathyroidism, who underwent parathyroid surgery, were included. ​Imaging results have been correlated to the perioperative drop in parathyroid hormone level and to the pathological analysis. ​Descriptive statistics are used, supplemented with 95% Clopper-Pearson confidence intervals for sensitivity and specificity and a sub-analysis with the McNemar test on paired data only. The per-lesion sensitivity of MET-PET/CT seems higher than that of [99mTc]-sestamibi or [99mTc]-tetrofosmin and [99mTc]-pertechnetate subtraction scintigraphy. The McNemar test, on paired data only, shows significantly higher sensitivity of MET-PET/CT compared to ultrasound (p=0.039) and significantly higher specificity of ultrasound compared to subtraction scintigraphy (p=0.035).​ MET-PET/CT after inconclusive or negative ultrasound and/or subtraction scintigraphy has an additional value in 70% of the cases.​ Preoperative parathyroid hormone levels were higher in patients in whom MET-PET/CT correctly predicted the pathological parathyroid glands, compared to those where MET-PET/CT missed at least one adenoma. The same trend was seen for 4-dimensional computed tomography. In conclusion, MET-PET/CT seems a valuable imaging modality in primary hyperparathyroidism, at least as second line imaging approach, with a higher per-lesion sensitivity than ultrasound in such setting. Especially when ultrasound and/or subtraction scintigraphy are inconclusive or negative, MET-PET/CT directs the surgeon to the correct localization of the parathyroid adenoma.

Inverted circadian variation of arterial pressure in a geriatric patient: an indicator of autonomic dysfunction.

BACKGROUND: Orthostatic hypotension (OH) in geriatric patients frequently involves a component of autonomic failure (AF). The combination of OH with nocturnal hypertension (NHT) is indicative of AF, which is described as pure (PAF), when neurologic symptoms are absent, or as multisystem atrophy (MSA), when combined with motor disturbance (Parkinsonism or Parkinson disease). CASE PRESENTATION: An 87-year-old man presented with long-lasting OH. He frequently fell, causing several fractures, and he developed heart failure. Blood pressure (BP) registration revealed a reversal of the day-night rhythm with NHT. An 18-FDG PET brain CT scan showed cerebellar hypometabolism, indicating MSA. CONCLUSIONS: This case demonstrates the use of continuous BP registration in geriatric patients with OH for diagnosing NHT. It illustrates the usefulness of 18-FDG PET brain CT scan to specify the nature of the AF. The case also illustrates the difficulty of managing the combination of OH and NHT.

Hyperprolactinemia in Acromegaly is Related to Prolactin Secretion by Somatolactotroph Tumours.

The aim of this study is to assess differences in patient characteristics, tumour characteristics and hormone levels between acromegalic patients with and without hyperprolactinemia. 44 patients of the University Hospital of Brussels, Belgium with acromegaly who were diagnosed between January 2007 and July 2018 were included in this study. Nineteen patients were classified in the hyperprolactinemia group and 25 patients were classified in the normoprolactinemia group. No significant differences between acromegalic patients with and without hyperprolactinemia were found in age at diagnosis, gender, presence of hyperprolactinemia symptoms, insulin-like growth factor 1, growth hormone and testosterone levels, tumour volume, tumour invasiveness, immunohistochemistry of growth hormone and prolactin, Ki-67 index and mitotic index. However, for a cut-off of 10% of prolactin-positive cells, there was a trend towards a higher percentage of prolactin-positive tumours in hyperprolactinemia patients (p=0.054) and higher mean prolactin level in case of positive prolactin immunostaining (p=0.007)). In our study there were no differences in characteristics between acromegaly patients with hyper- and normoprolactinemia. An association between the serum prolactin level and the positivity of prolactin immunohistochemistry of the adenoma tissue was found. The absence of a difference in tumour volume between patients with hyper- and normoprolactinemia suggests that the hyperprolactinemia is likely to be caused by the co-secretion of growth hormone and prolactin by the tumour. Finally, for the first time, the cut-off of 10% of prolactin cells was validated for the diagnosis of somatolactotroph tumours in acromegaly.

Leptomeningeal metastasis in a marginal zone lymphoma, presenting as a delirium: case report.

BACKGROUND: Hematologic malignancies can spread to the central nervous system (CNS), either as focal lesions or as leptomeningeal disease. Marginal zone lymphoma (MZL) is a low-grade non-Hodgkin lymphoma and generally presents as an indolent disease. This case report illustrates an unexpected diagnosis of leptomeningeal metastasis in an MZL, presenting as a delirium without B symptoms, pronounced hematologic progression or abnormalities on cerebral imaging. CASE PRESENTATION: An 80-year-old patient with a medical history of monoclonal B-cell lymphocytosis (MBL) with a clone indicative for an MZL, presented to the emergency and the geriatric departments with a recent cognitive deterioration and behavioral changes. MMSE score was 18/30. After excluding the most common etiologies through classical work-up including a normal head magnetic resonance imaging, a lumbar puncture was performed. In the cerebrospinal fluid an elevated protein level and increased lymphocyte count were identified, whereas beta-amyloid and tau protein levels were normal. Immunophenotyping of the lymphocytes confirmed CNS invasion by the MZL clone. Staging revealed mild splenomegaly. Prednisolone, intrathecal and systemic chemotherapy were initiated, leading to quick cognitive improvement with a final MMSE score of 28/30. CONCLUSIONS: To the best of our knowledge a delirium in an older patient due to leptomeningeal disease in MZL has never been described. To date, rare reports of CNS invasion by MZL describe focal intracranial lesions. After exclusion of common etiologies, physicians should remain vigilant when confronted with a patient with history of MBL presenting neurological symptoms. This case illustrates the importance of low threshold for lumbar punctures in this population, also for those patients with normal imaging studies.

Introduction of the orthogeriatric co-management model increases the quality of care : a pilot study.

Traditionally, geriatric patients with musculoskeletal or osteoarticular problems will be admitted to an orthopedic ward and will be treated by sur- geons. However, these patients often suffer from comorbidities requiring geriatric management. In this study, the orthogeriatric co-management (OG- CM) model is compared to traditional orthopedic care model in a retrospective pilot study. In this study, two patients groups were compared during two similar time periods : (1) Group 1 consisted of 119 geriatric patients admitted to an orthopedic (trauma) ward who were treated, with conventional geriatric care on demand (before OG- CM ; October 1-December 31, 2013) and (2) Group 2 consisted of 132 geriatric patients who were admitted after the implementation of the OG-CM model (after OG-CM ; October 1-December 31, 2014). Outcomes measured were : quality of care outcome, mortality and costs. After the introduction of OG-CM, the number of diagnoses increased (P = 0.011) adjusting for sex, age, length of stay (LOS), urgency and getting surgery (yes/ no). However, this did not lead to a significant higher severity of illness (SOI). The number of readmissions within a year were significantly lower after OG-CM (0.31 per patient) compared to before OG-CM (0.89 per patient) (P < 0.001). No significant difference in in-house and reported mortality after 3 months was observed. Costs increased, but no significant differences were found. The OG-CM model demonstrated an increase in quality of care. This was indicated by an increased number of medical diagnoses resulting in having less readmissions, without affecting the mortality rates and the LOS. Future randomized multi-centered studies are required to enable causal relationships.

Long-Term Treatment with Calcitriol in Postsurgical Hypoparathyroidism Leads to Renal Function Decline.

Hypoparathyroidism is a rare endocrine disease with insufficient parathyroid hormone levels. Replacing the missing hormone is not yet a standard therapy. The objective of this retrospective cohort study was to evaluate if the usual therapy regimens of postsurgical hypoparathyroidism with calcitriol have a negative effect on renal function. We performed a chart analysis of patients who were seen in a tertiary care hospital in Brussels, Belgium. A total of 101 subjects were identified as patients with permanent post-surgical hypoparathyroidism, based on the hospital records of patients who underwent a total thyroidectomy between 1996 and 2016, while still being treated with calcitriol. Patients with pre-existing renal insufficiency and/or active malignancy were excluded. The cohort was predominantly female of Caucasian origin. Renal function was evaluated before and after surgery (with a maximum follow-up of 12 years), using the CKD-EPI equation. A multivariate linear regression model was used to correlate renal function decline with the duration of calcitriol therapy, while correcting for the mean calcium phosphate product and age. We found a statistically significant (p=0.027) relationship between the duration of calcitriol treatment and renal function decline at a rate of 1.06 ml/min/1.73 m2 per year of calcitriol therapy. Our study, although being retrospective, is the first one to demonstrate a relationship between the cumulative use of calcitriol therapy and renal function decline.

A Systematic Review and Meta-Analysis of Endocrine-Related Adverse Events Associated with Immune Checkpoint Inhibitors.

Monoclonal antibodies targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4), programed cell death 1 (PD-1), or its ligand (PD-L1) have become the mainstay for advanced malignancies. The incidence of endocrine adverse events provoked by these immune checkpoint inhibitors (ICI) is based on data from randomized controlled trials, which have their drawbacks. PubMed was searched through August 22nd, 2017, by 2 reviewers independently (J.d.F. and C.E.A.). Early phase I/II, phase III experimental trials, prospective and retrospective observational studies were included. The weighted incidence and risk ratio were estimated for hypophysitis, primary thyroid disease, primary adrenal insufficiency, and diabetes mellitus. Their management is discussed in a systematic review. A total of 101 studies involving 19 922 patients were included. Ipilimumab-treated patients experienced hypophysitis in 5.6% (95% CI, 3.9-8.1), which was higher than nivolumab (0.5%; 95% CI, 0.2-1.2) and pembrolizumab (1.1%; 95% CI, 0.5-2.6). PD-1/PD-L1 inhibitors had a higher incidence of thyroid dysfunction - particularly hypothyroidism (nivolumab, 8.0%; 95% CI, 6.4-9.8; pembrolizumab, 8.5%; 95% CI, 7.5-9.7; PD-L1, 5.5%; 95% CI, 4.4-6.8; ipilimumab, 3.8%; 95% CI, 2.6-5.5). Combination therapy was associated with a high incidence of hypothyroidism (10.2-16.4%), hyperthyroidism (9.4-10.4%), hypophysitis (8.8-10.5%), and primary adrenal insufficiency (5.2-7.6%). Diabetes mellitus and primary adrenal insufficiency were less frequent findings on monotherapy. Our meta-analysis shows a high incidence of endocrine adverse events provoked by single agent checkpoint blockade, further reinforced by combined treatment.

Normocalcemic Primary Hyperparathyroidism: A Comparison with the Hypercalcemic Form in a Tertiary Referral Population.

Normocalcemic primary hyperparathyroidism (NPHPT) is a formally recognized variant of primary hyperparathyroidism (PHPT), characterized by normal total and ionized serum calcium concentrations and elevated parathyroid hormone (PTH) levels, in the absence of secondary causes for hyperparathyroidism. NPHPT has been studied previously, but data are limited and confounded. We aimed to compare the clinical and biochemical data of normocalcemic and hypercalcemic subjects in a hospital-based population.We retrospectively analysed the medical records of 131 subjects diagnosed with PHPT at the university hospital Brussels (UZ Brussel) between January 1st 2007 and December 31st 2016, including 25 normocalcemic and 106 hypercalcemic subjects.The mean values of age, BMI, sex, serum 25-OH vitamin D levels and urinary phosphate excretion were comparable between both groups. Subjects diagnosed with NPHPT had significantly lower plasma PTH levels, lower urinary calcium excretion and lower serum creatinine levels compared to the hypercalcemic subjects with PHPT. Corresponding eGFR values were higher in the normocalcemic group. Normocalcemic subjects (NPHPT) presented with a high prevalence of nephrolithiasis (36%), fragility fractures (12%) and osteoporosis (25%). Clinical manifestations and BMD measurements revealed no statistically significant differences between both groups.Our data show a relative prevalence of 19% NPHPT in PHPT. NPHPT may present the earliest form of PHPT with an extension in time, but is not an indolent disease state. Normocalcemic subjects should be managed as hypercalcemic subjects with PHPT. Further research regarding the pathophysiology and natural course of NPHPT is required.

Epileptic seizures and abnormal tooth development as primary presentation of pseudohypoparathyroidism type 1B.

Pseudohypoparathyroidism (PHP) is a rare genetic disorder characterised by a non-functioning PTH. Usually, the diagnosis is made following (symptomatic) hypocalcaemia. We describe a case in which epileptic seizures and abnormalities in dental development were the main clinical manifestation of PHP type 1B. This case demonstrates the importance of screening for hypocalcaemia in patients with de novo epileptic seizures. In addition, antiepileptic medications themselves may interfere with calcium-phosphate metabolism, causing or aggravating a hypocalcaemia as well. By correcting the calcium level, a resolution of these symptoms could be obtained.

Activated complement factor 3 is associated with liver fat and liver enzymes: the CODAM study.

BACKGROUND: The complement system may be involved in the pathogenesis of alcoholic and nonalcoholic liver disease, although studies in humans are scarce. For this reason, we investigated whether circulating levels of activated complement factor 3 (C3a) were associated with hepatic steatosis and hepatocellular damage. MATERIALS AND METHODS: Plasma C3a, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) were determined in 523 individuals (61% men, age 59 ± 7 years). Liver enzymes (LEs) were standardized and compiled into a LE score. Liver fat content was estimated using a predictive equation that has recently been validated with magnetic resonance spectrometry. Cross-sectional associations between C3a and liver fat or LE s were investigated with multiple linear regression analyses, stratified in no-to-moderate vs. heavy alcohol consumers (men: > 30 g/day; women: > 20 g/day). RESULTS: C3a was associated with liver fat percentage both in the no-to-moderate (ß = 0.223; 95%CI 0.036; 0.409) and in the heavy alcohol consumers (ß = 0.632; 95%CI 0.259-1.004; P-interaction = 0.047). C3a was also associated with the LE score in heavy alcohol consumers (ß = 0.917; 95%CI 0.443-1.392), but not in no-to-moderate alcohol consumers (ß = 0.042; 95%CI -0.198 to 0.281; P-interaction = 0.001). CONCLUSIONS: C3a levels, as a marker of complement activation, were associated with liver fat content and hepatocellular injury, at least in subjects who consume considerable amounts of alcohol daily.

Diabetes mellitus at the time of diagnosis of cirrhosis is associated with higher incidence of spontaneous bacterial peritonitis, but not with increased mortality.

DM (diabetes mellitus) is present in 20-40% of patients with liver cirrhosis, but its prognostic impact is unclear. Therefore, in the present study, we investigated whether the presence of DM in patients with cirrhosis was associated with increased mortality, and/or with increased incidence of SBP (spontaneous bacterial peritonitis). We reviewed medical and laboratory data of 230 patients with cirrhosis from the period 2001-2011, for whom data were complete in n=226. Follow-up for the outcomes mortality and SBP was performed until May 2012, with only 13 patients lost to follow-up. DM was present at baseline in 78 patients (35%). Median follow-up was 6.2 (interquartile range, 3.1-9.3) years, during which 118 patients died [47 out of 78 with DM (60%), and 71 out of 148 without DM (48%)]. The presence of DM at baseline was not associated with increased mortality after adjustment for age {HR (hazard ratio), 1.00 [95% CI (confidence interval), 0.67-1.50]}. Further adjustment for sex, aetiology of cirrhosis, platelet count and the Child-Pugh or MELD (model for end-stage liver disease) score did not change this finding. During follow-up, 37 patients developed incident SBP (19 with DM and 18 without DM). DM at baseline was associated with incident SBP, even after adjustment for age, sex, aetiology, platelet count and the Child-Pugh [HR, 2.39 (95% CI, 1.10-5.18)] or MELD score [HR, 2.50 (95% CI, 1.16-5.40)]. In conclusion, the presence of DM at baseline in patients with cirrhosis was associated with an increased risk of SBP, which may represent an increased susceptibility to infections. On the other hand, DM was not clearly associated with increased mortality in these patients.

Muscle Endurance and Self-Perceived Fatigue Predict Decline in Gait Speed and Activities of Daily Living After 1-Year Follow-Up: Results From the BUTTERFLY Study.

BACKGROUND: Fatigue might influence the losses in activities of daily living (ADL). When fatigue parameters are present before the experience of losses in ADL and gait speed, they can be used as early warning signals. This study aimed to explore the predictive value of muscle endurance and fatigue on changes in ADL and gait speed in community-dwelling older adults aged 80 and older. METHODS: Three hundred twenty four community-dwelling older adults aged 80 and older of the BUTTERFLY study were assessed after 1 year for muscle endurance, self-perceived fatigue, ADL, and gait speed. Exploratory factor analysis (EFA) was performed to explore, whether there is an underlying arrangement of the fatigue parameters. Mediating logistic regression analyses were used to investigate whether muscle endurance mediated by self-perceived fatigue predicts the decline in gait speed and ADL after 1-year follow-up. RESULTS: EFA indicated a 2-factor model (muscle endurance factor and self-perceived fatigue factor) and had a moderate fit (X2: 374.81, df: 2, comparative fit index; 0.710, Tucker-Lewis index (TLI): 0.961, root mean square error of approximation [90%]: 0.048 [0.00-0.90]). Muscle endurance mediated by self-perceived fatigue had an indirect effect on the prediction of decline in Basal-ADL (-0.27), Instrumental-ADL (-0.25), and gait speed (-0.28) after 1-year follow-up. CONCLUSION: This study showed that low muscle endurance combined with high self-perceived fatigue can predict changes in ADL after 1-year follow-up. These parameters might be very suitable for use in evaluating intrinsic capacity and can help to reduce the limitations in clinical usage of the vitality domain in the framework of intrinsic capacity.

Improved resistance to ischemia and reperfusion, but impaired protection by ischemic preconditioning in patients with type 1 diabetes mellitus: a pilot study.

BACKGROUND: In patients with type 1 diabetes mellitus (T1DM), cardiovascular events are more common, and the outcome following a myocardial infarction is worse than in nondiabetic subjects. Ischemic or pharmacological preconditioning are powerful interventions to reduce ischemia reperfusion (IR)-injury. However, animal studies have shown that the presence of T1DM can limit these protective effects. Therefore, we aimed to study the protective effect of ischemic preconditioning in patients with T1DM, and to explore the role of plasma insulin and glucose on this effect. METHODS: 99mTechnetium-annexin A5 scintigraphy was used to detect IR-injury. IR-injury was induced by unilateral forearm ischemic exercise. At reperfusion, Tc-annexin A5 was administered, and IR-injury was expressed as the percentage difference in radioactivity in the thenar muscle between the experimental and control arm 4 hours after reperfusion. 15 patients with T1DM were compared to 21 nondiabetic controls. The patients were studied twice, with or without ischemic preconditioning (10 minutes of forearm ischemia and reperfusion). Patients were studied in either normoglycemic hyperinsulinemic conditions (n=8) or during hyperglycemic normoinsulinemia (n=7). The controls were studied once either with (n=8) or without (n=13) ischemic preconditioning. RESULTS: Patients with diabetes were less vulnerable to IR-injury than nondiabetic healthy controls (12.8 ± 2.4 and 11.0 ± 5.1% versus 27.5 ± 4.5% in controls; p<0.05). The efficacy of ischemic preconditioning to reduce IR-injury, however, was lower in the patients and was even completely abolished during hyperglycemia. CONCLUSIONS: Patients with T1DM are more tolerant to forearm IR than healthy controls in our experimental model. The efficacy of ischemic preconditioning to limit IR-injury, however, is reduced by acute hyperglycemia. TRIAL REGISTRATION: The study is registered at www.clinicaltrials.gov (NCT00184821).

Lymphadenopathy after COVID-19 vaccination in patients with endocrine cancer: two case reports.

Summary: The Covid-19 vaccination has been rapidly implemented among patients with cancer. We present two cases of patients with endocrine tumours who developed lymphadenopathy following a Covid-19 vaccination. In the case of a patient with multiple endocrine neoplasia (MEN) 1 syndrome, an 18-fluorodeoxyglucose (18FDG)-PET/CT showed positive axillary lymph nodes. Further work-up with fine needle aspiration showed a reactive pattern following a Covid-19 vaccination in the ipsilateral arm shortly before the 18FDG-PET/CT. A second patient, in follow-up for thyroid cancer, developed clinical supraclavicular lymphadenopathy after a Covid-19 vaccination. Follow-up ultrasound proved the lesion to be transient. These cases demonstrate lymphadenopathy in response to a Covid-19 vaccination in two patients susceptible to endocrine tumours and metastatic disease. With growing evidence about the pattern and occurrence of lymphadenopathy after mRNA Covid-19 vaccination, recommendations for scheduling and interpretation of imaging among cancer patients should be implemented to reduce equivocal findings, overdiagnosis, and overtreatment, while maintaining a good standard of care in oncological follow-up. Learning points: Reactive lymphadenopathy is very common after an mRNA vaccination against Covid-19 and should be part of the differential diagnosis in patients with endocrine tumours who recently received a Covid-19 mRNA vaccination and present with an ipsilateral lymphadenopathy. A good vaccine history is essential in assessing the risk for lymphadenopathy and if possible, screening imaging in patients with endocrine tumours should be postponed at least 6 weeks after the previous vaccination. For now, a multidisciplinary care approach is recommended to determine the necessary steps in the diagnostic evaluation of lymphadenopathy in the proximity of a Covid-19 vaccination.