IMPORTANCE: Little is known about long-term sequelae of COVID-19. OBJECTIVE: To describe the consequences at 4 months in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS: In a ...prospective uncontrolled cohort study, survivors of COVID-19 who had been hospitalized in a university hospital in France between March 1 and May 29, 2020, underwent a telephone assessment 4 months after discharge, between July 15 and September 18, 2020. Patients with relevant symptoms and all patients hospitalized in an intensive care unit (ICU) were invited for further assessment at an ambulatory care visit. EXPOSURES: Survival of hospitalization for COVID-19. MAIN OUTCOMES AND MEASURES: Respiratory, cognitive, and functional symptoms were assessed by telephone with the Q3PC cognitive screening questionnaire and a checklist of symptoms. At the ambulatory care visit, patients underwent pulmonary function tests, lung computed tomographic scan, psychometric and cognitive tests (including the 36-Item Short-Form Health Survey and 20-item Multidimensional Fatigue Inventory), and, for patients who had been hospitalized in the ICU or reported ongoing symptoms, echocardiography. RESULTS: Among 834 eligible patients, 478 were evaluated by telephone (mean age, 61 years SD, 16 years; 201 men, 277 women). During the telephone interview, 244 patients (51%) declared at least 1 symptom that did not exist before COVID-19: fatigue in 31%, cognitive symptoms in 21%, and new-onset dyspnea in 16%. There was further evaluation in 177 patients (37%), including 97 of 142 former ICU patients. The median 20-item Multidimensional Fatigue Inventory score (n = 130) was 4.5 (interquartile range, 3.0-5.0) for reduced motivation and 3.7 (interquartile range, 3.0-4.5) for mental fatigue (possible range, 1 best to 5 worst). The median 36-Item Short-Form Health Survey score (n = 145) was 25 (interquartile range, 25.0-75.0) for the subscale “role limited owing to physical problems” (possible range, 0 best to 100 worst). Computed tomographic lung-scan abnormalities were found in 108 of 171 patients (63%), mainly subtle ground-glass opacities. Fibrotic lesions were observed in 33 of 171 patients (19%), involving less than 25% of parenchyma in all but 1 patient. Fibrotic lesions were observed in 19 of 49 survivors (39%) with acute respiratory distress syndrome. Among 94 former ICU patients, anxiety, depression, and posttraumatic symptoms were observed in 23%, 18%, and 7%, respectively. The left ventricular ejection fraction was less than 50% in 8 of 83 ICU patients (10%). New-onset chronic kidney disease was observed in 2 ICU patients. Serology was positive in 172 of 177 outpatients (97%). CONCLUSIONS AND RELEVANCE: Four months after hospitalization for COVID-19, a cohort of patients frequently reported symptoms not previously present, and lung-scan abnormalities were common among those who were tested. These findings are limited by the absence of a control group and of pre-COVID assessments in this cohort. Further research is needed to understand longer-term outcomes and whether these findings reflect associations with the disease.
Post-acute COVID-19 syndrome Montani, David; Savale, Laurent; Noel, Nicolas ...
European respiratory review,
03/2022, Letnik:
31, Številka:
163
Journal Article
Recenzirano
Odprti dostop
Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) pandemic that has resulted in millions of deaths and a major ...strain on health systems worldwide. Medical treatments for COVID-19 (anticoagulants, corticosteroids, anti-inflammatory drugs, oxygenation therapy and ventilation) and vaccination have improved patient outcomes. The majority of patients will recover spontaneously or after acute-phase management, but clinicians are now faced with long-term complications of COVID-19 including a large variety of symptoms, defined as "post-acute COVID-19 syndrome". Most studies have focused on patients hospitalised for severe COVID-19, but acute COVID-19 syndrome is not restricted to these patients and exists in outpatients. Given the diversity of symptoms and the high prevalence of persistent symptoms, the management of these patients requires a multidisciplinary team approach, which will result in the consumption of large amounts of health resources in the coming months. In this review, we discuss the presentation, prevalence, pathophysiology and evolution of respiratory complications and other organ-related injuries associated with post-acute COVID-19 syndrome.
Pituitary adenomas are benign intracranial neoplasms that can result in morbidity owing to local invasion and/or excessive or deficient hormone production. The prevalence of symptomatic pituitary ...adenomas is approximately 1:1,000 in the general population. The vast majority of these tumours occur sporadically and are not part of syndromic disorders. However, germline mutations in genes known to predispose individuals to familial pituitary adenomas are found in a few patients with sporadic pituitary adenomas. Mutations in AIP (encoding aryl-hydrocarbon receptor-interacting protein) are the most frequently observed germline mutations. The prevalence of these mutations in patients with sporadic pituitary adenomas is ∼4%, but can increase to 8-20% in young adults with macroadenomas or gigantism, and also in children. Germline mutations in MEN1 (encoding menin) result in multiple endocrine neoplasia type 1 and are found in very young patients with isolated sporadic pituitary adenomas, which highlights the importance of the chromosome 11q13 locus in pituitary tumorigenesis. In this Review, we describe the clinical features of patients with sporadic pituitary adenomas that are associated with AIP or MEN1 mutations, and discuss the molecular mechanisms that might be involved in pituitary adenoma tumorigenesis. We also discuss genetic screening of patients with sporadic pituitary adenomas and investigations of relatives of these patients who also have the same genetic mutations.
X-linked hypophosphatemia (XLH) is caused by mutations in the PHEX gene which result in Fibroblast Growth Factor-23 (FG-F23) excess and phosphate wasting. Clinically, XLH children present with ...rickets, bone deformities and short stature. In adulthood, patients may still be symptomatic with bone and joint pain, osteomalacia-related fractures or pseudofractures, precocious osteoarthrosis, enthesopathy, muscle weakness and severe dental anomalies. Besides these musculoskeletal and dental manifestations, adult XLH patients are also prone to secondary and tertiary hyperparathyroidism, cardiovascular and metabolic disorders. Pathophysiology of hyperparathyroidism is only partially understood but FGF23 excess and deficient production of calcitriol likely contributes to its development. Similarly, the pathophysiological mechanisms of potential cardiovascular and metabolic involvements are not clear, but FGF-23 excess may play an essential role. Treatment should be considered in symptomatic patients, patients undergoing orthopedic or dental surgery and women during pregnancy and lactation. Treatment with oral phosphate salts and active vitamin D analogs has incomplete efficacy and potential risks. Burosumab, a recombinant human monoclonal antibody against FGF-23, has proven its efficacy in phase 2 and phase 3 clinical trials in adult patients with XLH, but currently its position as first line or second line treatment differ among the countries.
•X-linked hypophosphatemia patients may have various symptoms in adulthood and require a multidisciplinary medical care.•Endocrine complications in adult XLH patients frequently include hyperparathyroidism and obesity.•Oral phosphate salts and active vitamin D should be proposed to symptomatic patients and patients with planed surgery.•Burosumab, a recombinant human antibody against FGF‑23, is a novel and effective therapeutic option for adult XLH patients.
Drug-Related Hypercalcemia Lecoq, Anne-Lise; Livrozet, Marine; Blanchard, Anne ...
Endocrinology and metabolism clinics of North America,
12/2021, Letnik:
50, Številka:
4
Journal Article
Recenzirano
Odprti dostop
This review focuses on the commonly prescribed medicaments that can be responsible for hypercalcemia, considering the prevalence, the predominant pathophysiological mechanisms, and the optimal ...medical management of each drug-induced hypercalcemia. Vitamin D supplements and 1α-hydroxylated vitamin D analogues increase intestinal calcium absorption, renal calcium reabsorption as well as bone resorption. In patients with hypoparathyroidism receiving recombinant human PTH, transient hypercalcemia can occur because of overtreatment, usually during acute illness. Thiazide-induced hypercalcemia is mainly explained by enhanced renal proximal calcium reabsorption, changing preexistent asymptomatic normocalcemic or intermittently hypercalcemic hyperparathyroidism into the classic hypercalcemic hyperparathyroidism. Lithium causes hypercalcemia mainly by drug-induced hyperparathyroidism.
Objectives
Whether COVID-19 leads to long-term pulmonary sequelae or not remains unknown. The aim of this study was to assess the prevalence of persisting radiological pulmonary fibrotic lesions in ...patients hospitalized for COVID-19.
Materials and methods
We conducted a prospective single-center study among patients hospitalized for COVID-19 between March and May 2020. Patients with residual symptoms or admitted into intensive care units were investigated 4 months after discharge by a chest CT (CCT) and pulmonary function tests (PFTs). The primary endpoint was the rate of persistent radiological fibrotic lesions after 4 months. Secondary endpoints included further CCT evaluation at 9 and 16 months, correlation of fibrotic lesions with clinical and PFT evaluation, and assessment of predictive factors.
Results
Among the 1151 patients hospitalized for COVID-19, 169 patients performed a CCT at 4 months. CCTs showed pulmonary fibrotic lesions in 19% of the patients (32/169). These lesions were persistent at 9 months and 16 months in 97% (29/30) and 95% of patients (18/19) respectively. There was no significant clinical difference based on dyspnea scale in patients with pulmonary fibrosis. However, PFT evaluation showed significantly decreased diffusing lung capacity for carbon monoxide (
p
< 0.001) and total lung capacity (
p
< 0.001) in patients with radiological lesions. In multivariate analysis, the predictive factors of radiological pulmonary fibrotic lesions were pulmonary embolism (OR = 9.0), high-flow oxygen (OR = 6.37), and mechanical ventilation (OR = 3.49).
Conclusion
At 4 months, 19% of patients investigated after hospitalization for COVID-19 had radiological pulmonary fibrotic lesions; they persisted up to 16 months.
Clinical relevance statement
Whether COVID-19 leads to long-term pulmonary sequelae or not remains unknown. The aim of this study was to assess the prevalence of persisting radiological pulmonary fibrotic lesions in patients hospitalized for COVID-19. The prevalence of persisting lesions after COVID-19 remains unclear. We assessed this prevalence and predictive factors leading to fibrotic lesions in a large cohort. The respiratory clinical impact of these lesions was also assessed.
Key Points
• Nineteen percent of patients hospitalized for COVID-19 had radiological fibrotic lesions at 4 months, remaining stable at 16 months.
• COVID-19 fibrotic lesions did not match any infiltrative lung disease pattern.
• COVID-19 fibrotic lesions were associated with pulmonary function test abnormalities but did not lead to clinical respiratory manifestation.
Abstract
Context
In patients with acromegaly on long-term treatment with long-acting somatostatin receptor ligands (SRLs), the time of blood collection for IGF-I measurement after injection is not ...well defined.
Objective
We aimed to assess serum IGF-I dynamics and variability in SRL-treated patients compared with surgically cured patients and healthy controls.
Methods
Thirty patients under SRLs considered controlled based on a normal previous IGF-I level, 10 patients cured by pituitary surgery, and 7 healthy subjects underwent 4 weekly IGF-I determinations.
Results
In SRL-treated patients, the IGF-I SDS (mean ± SD) was higher just before injection (0.34 ± 0.66) than at Day 7 (−0.33 ± 0.61; P = 0.0041) and Day 14 (−0.23 ± 0.60; P = 0.047) after injection, but it did not significantly vary in cured patients and healthy controls. The IGF-I CV was higher in SRL-treated patients than in cured patients or healthy controls (14.4 ± 7.6% vs 7.9 ± 4.4% and 8.3 ± 3.2%, respectively; P < 0.05 for both). Among SRL-treated patients, IGF-I CV was higher in “nonoptimally controlled patients”—i.e., patients with at least one elevated IGF-I value out of 4 (n = 9) compared with “optimally controlled” patients for whom all 4 IGF-I SDS values were < 2.0 (21.3 ± 9.3 vs 11.6 ± 6.0%; P = 0.0019). The latter did not differ from surgically cured patients and healthy controls. The measurement at the farthest distance from the SRL injection was the most predictive of patients with nonoptimally controlled disease.
Conclusion
In patients treated with long-acting SRLs, IGF-I sampling at the farthest distance from SRL injection is the most informative and best predictor of optimal disease control.
Organic Anion-Transporting Polypeptides (OATPs) are known to control the liver uptake of many drugs. Non-hepatic expression of OATPs has been reported although functional importance for whole-body ...pharmacokinetics (WBPK) remains unknown. Glyburide is a well described substrate of several hepatic and non-hepatic OATPs. Dynamic whole-body positron emission tomography (DWB-PET) with 11Cglyburide was performed in humans for determination of the importance of OATPs for liver uptake and WBPK. Seven healthy male subjects (24.7 ± 3.2 years) underwent 11Cglyburide PET scan with concomitant blood sampling. All subjects underwent baseline 11Cglyburide PET scan. Five subjects underwent a subsequent 11Cglyburide PET scan after infusion of the potent OATP inhibitor rifampicin (9 mg/kg i.v.). The transfer constant (kuptake) of 11Cglyburide from blood to the liver was estimated using the integration plot method. The tissue exposure of 11Cglyburide was described by the area under the time-activity curve (AUC) and corresponding tissue/blood ratio (AUCR). 11Cglyburide was barely metabolized in both the baseline and rifampicin conditions. Parent (unmetabolized) 11Cglyburide accounted for > 90 % of the plasma radioactivity. Excellent correlation was found between radioactive counting in arterial blood samples and in the image-derived input function, in both the baseline and rifampicin conditions (R2 = 97.9 %, p < 0.01). 11Cglyburide predominantly accumulated in the liver. Rifampicin decreased liver kuptake by 77.3 ± 7.3 %, which increased exposure in blood, kidneys, spleen, myocardium and brain (p < 0.05). No significant change in AUCR was observed except in the liver (p < 0.01). 11Cglyburide benefits from metabolic stability and high sensitivity to OATP inhibition which enables quantitative determination of OATP function. DWB-PET suggests negligible role for non-hepatic OATPs in controlling the tissue distribution of 11Cglyburide.
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•Organic Anion-Transporting Polypeptides (OATP) form a family of influx transporters.•Importance of hepatic and non-hepatic OATP on drug delivery in humans is not known.•Whole-body PET imaging using the OATP substrate 11C-glyburide was performed in humans.•11C-glyburide benefits from unmet imaging properties to explore OATP function in humans.•PET data suggest a liver-selective importance of OATP in controlling drug delivery.
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![[11C]glyburide PET imaging ...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0753-3322/small "[11C]glyburide PET imaging for quantitative determination of the importance of Organic Anion-Transporting Polypeptide transporter function in the human liver and whole-body")