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.

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.

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.

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.

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.

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.

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.

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.

COVID-19 and Cushing's disease in a patient with ACTH-secreting pituitary carcinoma.

SUMMARY: The pandemic caused by severe acute respiratory syndrome coronavirus 2 is of an unprecedented magnitude and has made it challenging to properly treat patients with urgent or rare endocrine disorders. Little is known about the risk of coronavirus disease 2019 (COVID-19) in patients with rare endocrine malignancies, such as pituitary carcinoma. We describe the case of a 43-year-old patient with adrenocorticotrophic hormone-secreting pituitary carcinoma who developed a severe COVID-19 infection. He had stabilized Cushing's disease after multiple lines of treatment and was currently receiving maintenance immunotherapy with nivolumab (240 mg every 2 weeks) and steroidogenesis inhibition with ketoconazole (800 mg daily). On admission, he was urgently intubated for respiratory exhaustion. Supplementation of corticosteroid requirements consisted of high-dose dexamethasone, in analogy with the RECOVERY trial, followed by the reintroduction of ketoconazole under the coverage of a hydrocortisone stress regimen, which was continued at a dose depending on the current level of stress. He had a prolonged and complicated stay at the intensive care unit but was eventually discharged and able to continue his rehabilitation. The case points out that multiple risk factors for severe COVID-19 are present in patients with Cushing's syndrome. 'Block-replacement' therapy with suppression of endogenous steroidogenesis and supplementation of corticosteroid requirements might be preferred in this patient population. LEARNING POINTS: Comorbidities for severe coronavirus disease 2019 (COVID-19) are frequently present in patients with Cushing's syndrome. 'Block-replacement' with suppression of endogenous steroidogenesis and supplementation of corticosteroid requirements might be preferred to reduce the need for biochemical monitoring and avoid adrenal insufficiency. The optimal corticosteroid dose/choice for COVID-19 is unclear, especially in patients with endogenous glucocorticoid excess. First-line surgery vs initial disease control with steroidogenesis inhibitors for Cushing's disease should be discussed depending on the current healthcare situation.

Undetectable thyroglobulin makes 123I whole-body scan and stimulated thyroglobulin obsolete in follow-up care of differentiated thyroid cancer: a retrospective study.

BACKGROUND: Differentiated thyroid cancer (DTC) is a common malignancy with increasing incidence. Follow-up care for DTC includes thyroglobulin (Tg) measurement and ultrasound (US) of the neck, combined with 131I remnant ablation when indicated. Diagnostic precision has evolved with the introduction of the new high-sensitive Tg-assays (sensitivity ≤0.1 ng/mL). The aim of the study was to determine the prognostic utility of high-sensitive Tg and the need for other diagnostic tests in DTC. METHODS: This was a retrospective, observational study. Patients with pathologically confirmed DTC, treated with total thyroidectomy and 131I remnant ablation, who had their complete follow-up care in our institution were selected (October 2013-December 2018). Subjects with possible thyroglobulin autoantibody interference were excluded. Statistical analysis was performed using the IBM SPSS® Statistics 24 software package. RESULTS: Forty patients were eligible for analysis. A total of 24 out of the 40 patients (60%) had an undetectable high-sensitive Tg 6 months after total thyroidectomy. None of these patients had a stimulated Tg above 1 ng/mL, or remnant on the 123I Whole-Body Scan (WBS) after 1 year of follow-up. Ultrasound of the neck, performed between 6 and 12 months postoperative, was negative in 21 out of the 24 patients. CONCLUSIONS: This study shows that an undetectable high-sensitive Tg can change the management of patients with DTC and decrease the use and need of stimulated Tg and 123I WBS.

Corrigendum: Consensus Recommendations for the Diagnosis and Management of X-Linked Hypophosphatemia in Belgium.

[This corrects the article DOI: 10.3389/fendo.2021.641543.].

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.

Consensus Recommendations for the Diagnosis and Management of X-Linked Hypophosphatemia in Belgium.

X-linked hypophosphatemia (XLH) is the most common genetic form of hypophosphatemic rickets and osteomalacia. In this disease, mutations in the PHEX gene lead to elevated levels of the hormone fibroblast growth factor 23 (FGF23), resulting in renal phosphate wasting and impaired skeletal and dental mineralization. Recently, international guidelines for the diagnosis and treatment of this condition have been published. However, more specific recommendations are needed to provide guidance at the national level, considering resource availability and health economic aspects. A national multidisciplinary group of Belgian experts convened to discuss translation of international best available evidence into locally feasible consensus recommendations. Patients with XLH may present to a wide array of primary, secondary and tertiary care physicians, among whom awareness of the disease should be raised. XLH has a very broad differential-diagnosis for which clinical features, biochemical and genetic testing in centers of expertise are recommended. Optimal care requires a multidisciplinary approach, guided by an expert in metabolic bone diseases and involving (according to the individual patient's needs) pediatric and adult medical specialties and paramedical caregivers, including but not limited to general practitioners, dentists, radiologists and orthopedic surgeons. In children with severe or refractory symptoms, FGF23 inhibition using burosumab may provide superior outcomes compared to conventional medical therapy with phosphate supplements and active vitamin D analogues. Burosumab has also demonstrated promising results in adults on certain clinical outcomes such as pseudofractures. In summary, this work outlines recommendations for clinicians and policymakers, with a vision for improving the diagnostic and therapeutic landscape for XLH patients in Belgium.

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.

Effect of Antihypertensive and Statin Medication Use on Muscle Performance in Community-Dwelling Older Adults Performing Strength Training.

OBJECTIVES: Antihypertensive drugs (AHTD) and statins have been shown to have effects beyond their primarily designed purpose; here we investigate their possible effect on muscle performance and strength in older adults following a physical exercise programme. DESIGN: The Senior PRoject INtensive Training (SPRINT) study is a randomised, controlled clinical trial designed to evaluate the effects of physical exercise on the immune system and muscle performance in older adults. PARTICIPANTS: In this secondary analysis, we included 179 independent participants (aged 65 years and above). We applied further categorisation based on medication use: AHTD (including, angiotensin-converting enzyme inhibitors [ACEI], angiotensin II receptor blockers [ARB], ß-blockers, and other AHTD) and statins. INTERVENTION: Participants were allocated randomly to one of the three exercise protocols: intensive strength training 3 times/week (3 × 10 repetitions at 80% of one-repetition maximum), strength endurance training (2 × 30 repetitions at 40% of one-repetition maximum), or control (passive stretching exercise) for 6 weeks. MEASUREMENTS: The change in maximal hand grip strength (GS), muscle fatigue resistance (FR), Muscle Strength Index (MSI), the 6-min walk test (6MWT), and Timed Up and Go Test (TUG) were assessed before and after 6 weeks of training. RESULTS: After 6 weeks, muscle strength (MSI and TUG) improved significantly in all training groups compared to baseline, independently of AHTD use. Moreover, AHTD had no effect on exercise improvements, with no significant differences between medication groups, except for TUG in ARB users, which exhibited a significantly lower performance. On the other hand, statin users presented a significantly longer FR time, indicating better performance compared to non-users. Finally, medication did not affect the participants' commitment to the training programme. CONCLUSION: Our study showed that statins and ARB usage might affect participant's response to strength training. Nevertheless, 6 weeks of training significantly improved muscle strength and performance irrespective of AHTD or statin use.

Pharmacologic Treatment for Hypoactive Delirium in Adult Patients: A Brief Report of the Literature.

OBJECTIVES: The purpose of this report was to identify medications that can be used to treat hypoactive delirium. DESIGN: A systematic search of PubMed and Web of Science from inception through September 20, 2020. SETTING AND PARTICIPANTS: Reports evaluating different pharmacologic treatments for hypoactive delirium in adults (age 18 years and older) and geriatric patients were included. METHODS: Three independent investigators reviewed the abstracts, using the Rayyan QCRI review tool to decide which articles were eligible for inclusion. Hereafter, articles were read completely for final inclusion. Study quality was assessed using the guidelines from the National Institute for Health and Care Excellence for cohort studies and randomized control trials. RESULTS: Of the 52 relevant articles, only 4 (8%) met the selection criteria. Two were cohort studies whereas the other 2 were randomized control trials. After further review, one of the reports was excluded because the same data were used as in one of the randomized control trials. In total, 4 different pharmacologic therapies were used in the selected studies: haloperidol, ziprasidone, aripiprazole, and methylphenidate. Aripiprazole showed a complete resolution of hypoactive delirium (P < .001), and methylphenidate showed a significant amelioration in cognitive function (P < .001). Ziprasidone and haloperidol did not show significant differences compared with placebo. CONCLUSIONS AND IMPLICATIONS: A limited number of clinical studies on the treatment of hypoactive delirium are available. Aripiprazole and methylphenidate showed promising results in the treatment of hypoactive delirium.

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.

Immune checkpoint inhibitors and type 1 diabetes mellitus: a case report and systematic review.

OBJECTIVE: To better define the rare adverse event (AE) of diabetes mellitus associated with immune checkpoint inhibitors (ICIs). DESIGN AND METHODS: We report the case of a lung cancer patient with diabetic ketoacidosis (DKA) and autoimmune thyroiditis during pembrolizumab treatment. We provide a systematic review of all published cases (PubMed/Web of Science/Cochrane, through November 2018) of autoimmune diabetes mellitus related to blockade of the cytotoxic T-lymphocyte antigen 4 (CTLA-4)-, programmed cell death 1 (PD-1) receptor or its ligand (PD-L1) or combination (ICI) therapy. RESULTS: Our literature search identified 90 patient cases (our case excluded). Most patients were treated with anti-PD-1 or anti-PD-L1 as monotherapy (79%) or in combination with CTLA-4 blockade (15%). On average, diabetes mellitus was diagnosed after 4.5 cycles; earlier for combination ICI at 2.7 cycles. Early-onset diabetes mellitus (after one or two cycles) was observed during all treatment regimens. Diabetic ketoacidosis was present in 71%, while elevated lipase levels were detected in 52% (13/25). Islet autoantibodies were positive in 53% of patients with a predominance of glutamic acid decarboxylase antibodies. Susceptible HLA genotypes were present in 65% (mostly DR4). Thyroid dysfunction was the most frequent other endocrine AE at 24% incidence in this patient population. CONCLUSION: ICI-related diabetes mellitus is a rare but often life-threatening metabolic urgency of which health-care professionals and patients should be aware. Close monitoring of blood glucose and prompt endocrine investigation in case of hyperglycemia is advisable. Predisposing factors such as HLA genotype might explain why some individuals are at risk.