A Learning Health System Approach to Long COVID Care.

Background: Global initiatives to mitigate COVID-19 transmission have shifted health system priorities to management of patients with prolonged long COVID symptoms. To better meet the needs of patients, clinicians, and systems, a learning health system approach can use rapid-cycle methods to integrate data and real-world experience to iteratively evaluate and adapt models of long COVID care. Observations: Employees in the Veterans Health Administration formed a multidisciplinary workgroup. We sought to develop processes to learn more about this novel long COVID syndrome and innovative long COVID care models that can be applied within and outside of our health care system. We describe our workgroup processes and goals to create a mechanism for cross-facility communication, identify gaps in care and research, and cocreate knowledge on best practices for long COVID care delivery. Conclusions: The learning health system approach will be critical in reimagining health care service delivery after the COVID-19 pandemic.

Cardiopulmonary Telerehabilitation.

Cardiopulmonary telerehabilitation is a safe and effective alternative to traditional center-based rehabilitation. It offers a sustainable solution to more conveniently meet the needs of patients with acute or chronic, preexisting or newly acquired, cardiopulmonary diseases. To maximize success, programs should prioritize basic, safe, and timely care options over comprehensive or complex approaches. The future should incorporate new strategies learned during a global pandemic and harness the power of information and communication technology to provide evidence-based patient-centered care. This review highlights clinical considerations, current evidence, recommendations, and future directions of cardiopulmonary telerehabilitation.

Novel GNE mutations in autosomal recessive hereditary inclusion body myopathy patients.

Hereditary Inclusion Body Myopathy (HIBM, IBM2, MIM:600737) is an autosomal recessive adult onset progressive muscle wasting disorder. It is associated with the degeneration of distal and proximal muscles, while often sparing the quadriceps. The bifunctional enzyme UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE/MNK), encoded by the GNE gene, catalyzes the first two committed, rate-limiting steps in the biosynthesis of N-acetylneunaminic acid (sialic acid). Affected individuals have been identified with mutations in the GNE gene. In the present study, the GNE coding region of 136 symptomatic patients were sequenced. A total of 41 patients were found to have GNE mutations. Eight novel mutations were discovered among seven patients. Of the eight novel mutations, seven were missense (p.I150V, p.Y186C, p.M265T, p.V315T, p.N317D, p.G669R, and p.S699L) and one was nonsense (p.W495X), all of which span the epimerase, kinase, and allosteric domains of GNE. In one patient, one novel mutation was found in the allosteric region and kinase domain of the GNE gene. Mutations in the allosteric region lead to a different disease, sialuria; however, this particular mutation has not been described in patients with sialuria. The pathological significance of this variation with GNE function remains unknown and further studies are needed to identify its connection with HIBM. These findings further expand the clinical and genetic spectrum of HIBM.

Serum neural cell adhesion molecule is hyposialylated in hereditary inclusion body myopathy.

Hereditary inclusion body myopathy (HIBM) is a young-adult onset autosomal recessive disorder caused by a hypomorphic rate limiting enzyme of sialic acid biosynthesis. The enzyme is UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, and is encoded by the GNE gene. HIBM causes slowly progressive muscle weakness and atrophy. Patients are typically diagnosed at 20-30 years of age, and most patients are incapacitated and wheelchair-confined by 30-50 years of age. Some sialic acid containing glycoproteins, including neural cell adhesion molecule (NCAM), are hyposialylated in HIBM muscle biopsy samples. We developed a method to allow detection of serum NCAM sialylation using Western blot, and tested serum samples from several patients and a HIBM mouse model. Preliminary results showed a clear difference in polysialylated and hyposialylated forms of NCAM extracted from serum, and showed NCAM is hyposialylated in HIBM serum samples. This initial finding may prove useful in reducing the need for serial muscle biopsies in HIBM treatment trials. Additional studies are underway to further validate this finding and to evaluate the specificity, reliability, and robustness of this potential serum biomarker for HIBM.