Eur Respir Rev. 2023 Feb 7;32(167):220161. doi: 10.1183/16000617.0161-2022. Print 2023 Mar 31.

ABSTRACT

The world of rare interstitial lung diseases (ILDs) is diverse and complex. Diagnosis and therapy usually pose challenges. This review describes a selection of rare and ultrarare ILDs including pulmonary alveolar proteinosis, pulmonary alveolar microlithiasis and pleuroparenchymal fibroelastosis. In addition, monogenic ILDs or ILDs in congenital syndromes and various multiple cystic lung diseases will be discussed. All these conditions are part of the scope of the European Reference Network on rare respiratory diseases (ERN-LUNG). Epidemiology, pathogenesis, diagnostics and treatment of each disease are presented.

PMID:36754433 | DOI:10.1183/16000617.0161-2022

Int J Technol Assess Health Care. 2023 Feb 7;39(1):e10. doi: 10.1017/S0266462323000053.

ABSTRACT

BACKGROUND: Out of 185 orphan medicinal products (OMPs) registered in 2015-2021, a mere 110 (59 percent) were available to Czech patients, and only 54 (29 percent) were officially reimbursed. Moreover, this proportion has steadily decreased over time. After years of public debate induced by this unsatisfactory OMP patient access, the national viewpoint shifted toward creating a special pathway for the reimbursement of OMP. Thus, a rigorous pricing and reimbursement procedure with strict timelines and elaborated methodology has been recently adopted in Czechia.

METHODOLOGY: The innovative legislation follows the recommendations for value assessment and funding processes for rare diseases and incorporates additional elements of value, such as the societal perspective. First, the application with clinical evidence, cost-effectiveness, and budget impact analyses is submitted to the governmental health technology assessment (HTA) agency by the Marketing Authorization Holder or a Health Insurance Fund. Moreover, professional associations and patients' organizations are rightful participants in the proceeding, providing evidence and comments. Then, the HTA agency performs the assessment/appraisal of the evidence. It subsequently publishes the assessment report summarizing available information. The report is then forwarded to the Ministry of Health and its advisory body consisting of patients, clinical experts, health insurance funds, and the State. They critically evaluate the documents and issue a binding opinion following prespecified decision-making criteria. Based on this binding opinion, the decision is issued by the HTA agency. Thus, the role of the advisory body in this process is crucial.

CONCLUSION: We believe that this novel approach may offer satisfactory patient access to orphan drugs. Moreover, it serves as a real-world example of "value-based" decision making.

PMID:36748356 | DOI:10.1017/S0266462323000053

Anatol J Cardiol. 2023 Feb;27(2):106-112. doi: 10.14744/AnatolJCardiol.2022.2235.

ABSTRACT

BACKGROUND: Isolated complete atrioventricular block is a rare disease often associated with maternal autoantibodies. This study aimed to present the midterm data of patients at our clinic diagnosed with isolated complete atrioventricular block.

METHODS: We evaluated 108 patients diagnosed with isolated complete atrioventricular block. Demographic data of the patients, electrocardiography, echocardiography, 24-hour Holter monitoring data, and follow-up and complications of the patients who underwent pacemaker implantation were evaluated retrospectively.

RESULTS: The mean age of the patients at diagnosis was 5.51 ± 5.05 years. At the time of diagnosis, 74.8% of the patients had no symptoms associated with complete atrioventricular block. The most common symptom was fatigue. Pacemaker implantation was needed in 88 (81.4%) patients during follow-up. Significant bradycardia was the most common pacemaker implantation indication. The mean battery life was 5.41 ± 2.65 years. The battery replacement-free period of 68 patients who underwent pacemaker implantation and continued their follow-up was 4.18 ± 2.89 (0.1-10) years. Pacemaker-related complications developed in 8 patients during follow-up. Left ventricular dysfunction developed (dyssynchrony induced) in 3 patients at follow-up, and all were paced from the right ventricular anterior wall. Those patients underwent cardiac resynchronization therapy and their left ventricular dysfunction improved.

CONCLUSION: Isolated complete atrioventricular block is a rare disease requiring careful clinical follow-up. Patients are often asymptomatic and significant bradycardia is the most common indication for pacemaker implantation. Left ventricular dysfunction is an important cause of morbidity, especially in patients with right ventricular anterior wall pacing. Physicians should be aware of left ventricular dysfunction during follow-up. Cardiac resynchronization therapy should be considered as a treatment option for left ventricular dysfunction.

PMID:36747457 | DOI:10.14744/AnatolJCardiol.2022.2235

BMC Med Educ. 2023 Feb 6;23(1):93. doi: 10.1186/s12909-023-04079-6.

ABSTRACT

BACKGROUND: The nature of student learning in problem-based learning (PBL) largely depends on the quality of the case scenarios presented to them. The effect of case scenarios with higher challenge degree, especially common disease with atypical symptoms (CDAS)- and rare disease (RD)-based case scenarios, on undergraduate medical students remains unclear. This study compared the impact of all scenarios pertaining to common disease with typical symptoms (CDTS) case scenarios, CDTS interspersed with CDAS case scenarios, and CDTS interspersed with RD case scenarios on perceptions of undergraduate students studying organ/system integration curriculum via PBL.

METHODS: After finishing four CDTS case scenarios, 294 third-year medical students were randomly allocated into three groups: CDTS, CDAS and RD, studying via CDTS, CDAS and RD case scenarios, respectively. A questionnaire with 15 items was conducted to evaluate the students' perceptions. The students' responses were scored using a 4-point rating scale. The data were analysed using the Kruskal-Wallis test.

RESULTS: Among the three PBL conditions, the ones with a higher degree of challenge were rated higher by the students, which included the quality of the case scenarios and the overall performances of the students. The CDAS and RD cases were more effective in developing students' self-directed learning skills, stimulating them to acquire more knowledge required for future work. The satisfaction percentage of RD case scenario sessions was higher.

CONCLUSIONS: Of all the three kinds of case scenarios, both CDTS interspersed with CDAS and RD case scenarios had more positive effects on the self-evaluated performance of students. Increasing the challenge and variety of case scenarios by the inclusion of CDAS and RD especially RD might be an effective stimulus in improving students' performance in PBL sessions.

PMID:36747223 | DOI:10.1186/s12909-023-04079-6

Proc Natl Acad Sci U S A. 2023 Feb 14;120(7):e2217831120. doi: 10.1073/pnas.2217831120. Epub 2023 Feb 6.

ABSTRACT

Myopathy is the main adverse effect of the widely prescribed statin drug class. Statins exert their beneficial effect by inhibiting HMG CoA-reductase, the rate-controlling enzyme of the mevalonate pathway. The mechanism of statin myopathy is yet to be resolved, and its treatment is insufficient. Through homozygosity mapping and whole exome sequencing, followed by functional analysis using confocal microscopy and biochemical and biophysical methods, we demonstrate that a distinct form of human limb girdle muscular disease is caused by a pathogenic homozygous loss-of-function missense mutation in HMG CoA reductase (HMGCR), encoding HMG CoA-reductase. We biochemically synthesized and purified mevalonolactone, never administered to human patients before, and establish the safety of its oral administration in mice. We then show that its oral administration is effective in treating a human patient with no significant adverse effects. Furthermore, we demonstrate that oral mevalonolactone resolved statin-induced myopathy in mice. We conclude that HMGCR mutation causes a late-onset severe progressive muscular disease, which shows similar features to statin-induced myopathy. Our findings indicate that mevalonolactone is effective both in the treatment of hereditary HMGCR myopathy and in a murine model of statin myopathy. Further large clinical trials are in place to enable the clinical use of mevalonolactone both in the rare orphan disease and in the more common statin myopathy.

PMID:36745799 | DOI:10.1073/pnas.2217831120

Am J Physiol Cell Physiol. 2023 Feb 6. doi: 10.1152/ajpcell.00002.2023. Online ahead of print.

ABSTRACT

Congenital myopathies are a vast group of genetic muscle diseases. Among the causes are mutations in the MYH2 gene resulting in truncated type IIa myosin heavy chains (MyHCs). The precise cellular and molecular mechanisms by which these mutations induce skeletal muscle symptoms remain obscure. Hence, in the present study, we aimed to explore whether such genetic defects would alter the presence as well as the post-translational modifications of MyHCs and the functionality of myosin molecules. For this, we dissected muscle fibres from four myopathic patients with MYH2 truncating mutations and from five human healthy controls. We then assessed MyHCs presence/post-translational modifications using LC/MS; relaxed myosin conformation and concomitant ATP consumption with a loaded Mant-ATP chase set-up; and myosin activation with an unloaded in vitro motility assay. Interestingly, the type IIa MyHC with one additional acetylated lysine (Lys35-Ac) was present in the patients. This was accompanied by a higher ATP demand of myosin heads in the disordered-relaxed conformation as well as by faster actomyosin kinetics. Overall, our findings indicate that MYH2 truncating mutations impact myosin presence/functionality in human adult mature myofibres by disrupting the ATPase activity and actomyosin complex. These are likely important molecular pathological disturbances leading to the myopathic phenotype in patients.

PMID:36745529 | DOI:10.1152/ajpcell.00002.2023

EMBO Rep. 2023 Feb 6:e55571. doi: 10.15252/embr.202255571. Online ahead of print.

ABSTRACT

Bardet-Biedl syndrome (BBS) is a ciliopathy characterized by retinal degeneration, obesity, renal abnormalities, postaxial polydactyly, and developmental defects. Genes mutated in BBS encode for components and regulators of the BBSome, an octameric complex that controls the trafficking of cargos and receptors within the primary cilium. Although both structure and function of the BBSome have been extensively studied, the impact of ubiquitin signaling on BBSome is largely unknown. We identify the E3 ubiquitin ligase PJA2 as a novel resident of the ciliary compartment and regulator of the BBSome. Upon GPCR-cAMP stimulation, PJA2 ubiquitylates BBSome subunits. We demonstrate that ubiquitylation of BBS1 at lysine 143 increases the stability of the BBSome and promotes its binding to BBS3, an Arf-like GTPase protein controlling the targeting of the BBSome to the ciliary membrane. Downregulation of PJA2 or expression of a ubiquitylation-defective BBS1 mutant (BBS1K143R ) affects the trafficking of G-protein-coupled receptors (GPCRs) and Shh-dependent gene transcription. Expression of BBS1K143R in vivo impairs cilium formation, embryonic development, and photoreceptors' morphogenesis, thus recapitulating the BBS phenotype in the medaka fish model.

PMID:36744302 | DOI:10.15252/embr.202255571

G Ital Cardiol (Rome). 2023 Feb;24(2):127-135. doi: 10.1714/3963.39421.

ABSTRACT

Cardiac amyloidosis, in the three forms of immunoglobulin light chain (AL), transthyretin (ATTR) wild type (ATTRwt) and mutated (ATTRv) amyloidosis, is an increasingly known and recognized disease in the cardiovascular setting. The first stage of the patient's journey is the clinical suspicion of the disease, which is placed, in presence of a hypertrophic phenotype, by the identification of red flags, both extracardiac and cardiac clues whose presence increase the probability of being faced with a patient with this disease. The second stage is represented by diagnosis, which occurs with certainty through the identification of amyloid substance in cardiac tissue. This stage is spotted in wo parts, i.e. disease confirmation and disease etiology definition (AL vs ATTRwt vs ATTRv). However, it is possible in some selected cases to make a diagnosis of ATTR without the need for tissue assessment, in presence of a positive grade 2-3 bisphosphonate scintigraphy and absence of monoclonal component. Once the diagnosis has been made, the third stage is the assessment of prognosis, the fourth is the patient therapy pathway and fifth is the follow-up plan. Prognosis evaluation is based on different staging systems at the onset of the disease, whose applicability in the era of new effective therapies is still to be defined. To date, the transthyretin tetramer stabilizer tafamidis is the only approved treatment for both wild-type and mutant ATTR cardiomyopathy without polyneuropathy, while ATTRv with associated neuropathy can benefit from treatment with patisiran, an inhibitor of hepatic protein synthesis. Therapies for complications and comorbidities, must be addressed individually, due to the lack of specific clinical trials on this category of patients. In fact, it is important to take into consideration the risks linked to the use of some drugs due to the infiltration of the conduction tissue by the amyloid substance, which increases the risk of bradycardia and heart blocks, the tendency towards hypotension and the increased thromboembolic risk. It is also essential to follow the course of the disease and the efficacy of the treatment in affected patients with a standardized follow-up, and to identify early the signs/symptoms of the disease in asymptomatic TTR mutation carriers.This ANMCO position paper on amyloidosis aims to provide the clinical cardiologist with a practical summary of the disease, to accompany the patient with amyloidosis in the various stages of his journey.

PMID:36735312 | DOI:10.1714/3963.39421

Curr Opin Allergy Clin Immunol. 2023 Apr 1;23(2):158-163. doi: 10.1097/ACI.0000000000000869. Epub 2022 Nov 2.

ABSTRACT

PURPOSE OF REVIEW: Paediatric mastocytosis is a rare clonal disorder characterized by the overproduction and organ infiltration of mast cells. Symptoms are due to mast cell mediator release. Cutaneous mastocytosis is the most common presentation in children with systemic disease being rare. Our aim is to provide a practical guideline in differentiating subtypes of paediatric mastocytosis while providing actionable recommendations on diagnosis, clinical management, follow-up and prognosis.

RECENT FINDINGS: Longitudinal cohort studies of paediatric cutaneous mastocytosis have shown spontaneous remission with favourable prognosis. Hereditary alpha-tryptasemia may coexist with mastocytosis; thus, screening for this disorder is recommended. There is an emerging role for serum tryptase in asthma endotyping and potential for using therapeutic tryptase inhibitors.

SUMMARY: Morbidity in paediatric mastocytosis typically arises from symptoms secondary to mast cell mediator release. Prognosis for nonaggressive disease is typically favourable; however, risks for anaphylaxis and psychosocial morbidity may be underestimated. Symptomatic management and anticipatory guidance may help support patients and families throughout the disease course.

PMID:36730855 | DOI:10.1097/ACI.0000000000000869

Drugs. 2023 Feb;83(2):117-134. doi: 10.1007/s40265-022-01824-x. Epub 2023 Feb 2.

ABSTRACT

Systemic lupus erythematosus (SLE) is characterized by an aberrant immune response, leading to an extremely heterogeneous clinical presentation, potentially affecting different systems and organs. Despite the fact that SLE mortality has greatly decreased since the introduction of steroids, some forms of refractory/severe SLE still have the potential to result in permanent organ damage as well as increased mortality and morbidity. Furthermore, SLE patients with multiple comorbidities may face a clinical conundrum and have a bad prognosis. An improved prognosis for severe refractory SLE depends on prompt and appropriate treatment. Due to the scarcity of solid data from a well-characterized group of patients with refractory/severe SLE coming from randomized controlled studies, this review aims to shed light on this with real-world evidence from clinical research performed at our Unit, the University Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases with Nephrology and Dialysis Unit and Center of Immuno-Rheumatology and Rare Diseases (CMID) (Turin, Italy). In order to determine the key clinical and prognostic features, and therapeutic approaches for severe and/or refractory SLE, our experience will be described together with existing literature, primarily focused on dermatological, neuropsychiatric, and renal symptoms.

PMID:36729344 | DOI:10.1007/s40265-022-01824-x

Clin Nucl Med. 2023 Mar 1;48(3):273-275. doi: 10.1097/RLU.0000000000004479. Epub 2022 Dec 24.

ABSTRACT

Intracranial syphilitic gumma is a rare neurological disease. We present 68Ga-DOTA-FAPI-04 and 18F-FDG PET/CT findings of intracranial syphilitic gumma in a 46-year-old man with HIV. In this case, 68Ga-DOTA-FAPI-04 PET/CT outperforms 18F-FDG in helping to visualizing syphilitic gumma. Syphilitic gumma can also cause increase FAPI activity. Our findings suggest the potential value of 68Ga-DOTA-FAPI-04 in the diagnosis of syphilis.

PMID:36723888 | DOI:10.1097/RLU.0000000000004479

J Med Case Rep. 2023 Feb 1;17(1):31. doi: 10.1186/s13256-022-03746-4.

ABSTRACT

BACKGROUND: Presacral myelolipomas form a rare disease and are often found incidentally in imaging diagnostics.

CASE PRESENTATION: In this study, we report the case of a 71-year-old caucasian female with an incidental finding of a retroperitoneal tumor on magnetic resonance imaging scan. This report aimed at presenting the clinical course of this patient with emphasis on analysis of pathological, clinical, and epidemiological features in a meta-analysis of reported cases.

CONCLUSION: Presacral myelolipomas are rare and its etiology remains unclear. Surgical resection is indicated in symptomatic lesions and lesions > 4 cm. More clinical and pathological research on this rare entity is warranted.

PMID:36721209 | DOI:10.1186/s13256-022-03746-4

Orphanet J Rare Dis. 2023 Jan 31;18(1):20. doi: 10.1186/s13023-023-02619-3.

ABSTRACT

Pre-clinical research and development relies heavily upon translationally valid models of disease. A major difficulty in understanding the biology of, and developing treatments for, rare disease is the lack of animal models. It is important that these models not only recapitulate the presentation of the disease in humans, but also that they share functionally equivalent underlying genetic causes. Nonhuman primates share physiological, anatomical, and behavioral similarities with humans resulting from close evolutionary relationships and high genetic homology. As the post-genomic era develops and next generation sequencing allows for the resequencing and screening of large populations of research animals, naturally occurring genetic variation in nonhuman primates with clinically relevant phenotypes is regularly emerging. Here we review nonhuman primate models of multiple rare genetic diseases with a focus on the similarities and differences in manifestation and etiologies across species. We discuss how these models are being developed and how they can offer new tools and opportunities for researchers interested in exploring novel therapeutics for these and other genetic diseases. Modeling human genetic diseases in translationally relevant nonhuman primates presents new prospects for development of therapeutics and a better understanding of rare diseases. The post-genomic era offers the opportunity for the discovery and further development of more models like those discussed here.

PMID:36721163 | DOI:10.1186/s13023-023-02619-3

Am J Med Genet A. 2023 Feb 1. doi: 10.1002/ajmg.a.63128. Online ahead of print.

ABSTRACT

Tethered cord syndrome (TCS) is characterized by leg pain and weakness, bladder and bowel dysfunction, orthopedic malformations such as scoliosis, and motor deficits caused by the fixation of the spinal cord to surrounding tissues. TCS is surgically treatable and often found in conjunction with other syndromic conditions. KBG syndrome is caused by variants in the ANKRD11 gene and is characterized by short stature, developmental delay, macrodontia, and a triangular face. The current study explores the prevalence of TCS in pediatric KBG patients and their associated signs and symptoms. Patients with KBG were surveyed for signs and symptoms associated with TCS and asked if they had been diagnosed with the syndrome. We found a high proportion of patients diagnosed with (11%) or being investigated for TCS (24%), emphasizing the need to further characterize the comorbid syndromes. No signs or symptoms clearly emerged as indicative of TCS in KBG patients, but some the prevalence of some signs and symptoms varied by sex. Male KBG patients with diagnosed TCS were more likely to have coordination issues and global delay/brain fog than their female counterparts. Understanding the presentation of TCS in KBG patients is critical for timely diagnosis and treatment.

PMID:36722669 | DOI:10.1002/ajmg.a.63128

J Inherit Metab Dis. 2023 Jan 31. doi: 10.1002/jimd.12595. Online ahead of print.

ABSTRACT

Congenital disorders of glycosylation (CDG) and Niemann-Pick type C (NPC) disease are inborn errors of metabolism that can both present with infantile-onset severe liver disease and other multisystemic manifestations. Plasma bile acid and N-palmitoyl-O-phosphocholineserine (PPCS) are screening biomarkers with proposed improved sensitivity and specificity for NPC. We report an infant with ATP6AP1-CDG who presented with cholestatic liver failure and elevated plasma oxysterols and bile acid, mimicking NPC clinically and biochemically. On further investigation, PPCS, but not the bile acid derivative N-(3β,5α,6β-trihydroxy-cholan-24-oyl) glycine (TCG), were elevated in plasma samples from individuals with ATP6AP1-, ALG1-, ALG8-, and PMM2-CDG. These findings highlight the importance of keeping CDG within the diagnostic differential when evaluating children with early onset severe liver disease and elevated bile acid or PPCS to prevent delayed diagnosis and treatment.

PMID:36719165 | DOI:10.1002/jimd.12595

Front Immunol. 2023 Jan 13;13:1099918. doi: 10.3389/fimmu.2022.1099918. eCollection 2022.

ABSTRACT

Scleromyxedema is a rare idiopathic fibromucinous disorder characterized by a generalized papular and sclerodermoid cutaneous eruption. Patients often have praraproteinemia and extracutaneous, even lethal, manifestations. Yet the prognostic and therapeutic features of scleromyxedema are poorly documented. High-dose intravenous immunoglobulin (IVIG), used either alone or in conjunction with systemic steroids and/or thalidomide, has been suggested as a first-line treatment. We report the case of a 45-year-old woman diagnosed with scleromyxedema with paraproteinemia that initially did not respond to systemic steroids, retinoids, and thalidomide but greatly improvement in terms of systemic and cutaneous symptoms after treatment with IVIG.

PMID:36713453 | PMC:PMC9880447 | DOI:10.3389/fimmu.2022.1099918

J Indian Assoc Pediatr Surg. 2022 Nov-Dec;27(6):747-750. doi: 10.4103/jiaps.jiaps_4_22. Epub 2022 Nov 14.

ABSTRACT

Pancreatoblastoma, an orphan disease, is the most common malignant epithelial neoplasm of the pancreas in children. With vague clinical features, diagnosis is made by radiological suggestions and histopathology. The presence of metastatic disease and inoperable/incomplete excision remains the poor prognostic markers. We present a rare instance of an adolescent who has survived metastatic pancreatoblastoma after neoadjuvant chemoreduction/complete surgical excision.

PMID:36714488 | PMC:PMC9878534 | DOI:10.4103/jiaps.jiaps_4_22

Annu Rev Med. 2023 Jan 27;74:489-502. doi: 10.1146/annurev-med-042921-110721.

ABSTRACT

Exome sequencing (ES) and genome sequencing (GS) have radically transformed the diagnostic approach to undiagnosed rare/ultrarare Mendelian diseases. Next-generation sequencing (NGS), the technology integral for ES, GS, and most large (100+) gene panels, has enabled previously unimaginable diagnoses, changes in medical management, new treatments, and accurate reproductive risk assessments for patients, as well as new disease gene discoveries. Yet, challenges remain, as most individuals remain undiagnosed with current NGS. Improved NGS technology has resulted in long-read sequencing, which may resolve diagnoses in some patients who do not obtain a diagnosis with current short-read ES and GS, but its effectiveness is unclear, and it is expensive. Other challenges that persist include the resolution of variants of uncertain significance, the urgent need for patients with ultrarare disorders to have access to therapeutics, the need for equity in patient access to NGS-based testing, and the study of ethical concerns. However, the outlook for undiagnosed disease resolution is bright, due to continual advancements in the field.

PMID:36706750 | DOI:10.1146/annurev-med-042921-110721

Comput Biol Med. 2023 Mar;154:106555. doi: 10.1016/j.compbiomed.2023.106555. Epub 2023 Jan 13.

ABSTRACT

Hypopharyngeal cancer (HPC) is a rare disease. Therefore, it is a challenge to automatically segment HPC tumors and metastatic lymph nodes (HPC risk areas) from medical images with the small-scale dataset. Combining low-level details and high-level semantics from feature maps in different scales can improve the accuracy of segmentation. Herein, we propose a Multi-Modality Transfer Learning Network with Hybrid Bilateral Encoder (Twist-Net) for Hypopharyngeal Cancer Segmentation. Specifically, we propose a Bilateral Transition (BT) block and a Bilateral Gather (BG) block to twist (fuse) high-level semantic feature maps and low-level detailed feature maps. We design a block with multi-receptive field extraction capabilities, M Block, to capture multi-scale information. To avoid overfitting caused by the small scale of the dataset, we propose a transfer learning method that can transfer priors experience from large computer vision datasets to multi-modality medical imaging datasets. Compared with other methods, our method outperforms other methods on HPC dataset, achieving the highest Dice of 82.98%. Our method is also superior to other methods on two public medical segmentation datasets, i.e., the CHASE_DB1 dataset and BraTS2018 dataset. On these two datasets, the Dice of our method is 79.83% and 84.87%, respectively. The code is available at: https://github.com/zhongqiu1245/TwistNet.

PMID:36701967 | DOI:10.1016/j.compbiomed.2023.106555

Nursing. 2023 Feb 1;53(2):24-30. doi: 10.1097/01.NURSE.0000905700.44849.f4.

ABSTRACT

Amyotrophic lateral sclerosis (ALS) is a rare and serious disease affecting approximately 20,000 people in the US. This article details the signs, symptoms, and diagnosis of ALS and important management considerations.

PMID:36700810 | DOI:10.1097/01.NURSE.0000905700.44849.f4