Longitudinal Muscle Biopsies Reveal Inter- and Intra-Subject Variability in Cancer Cachexia: Paving the Way for Biopsy-Guided Tailored Treatment.

In the rapidly evolving landscape of cancer cachexia research, the development and refinement of diagnostic and predictive biomarkers constitute an ongoing challenge. This study aims to introduce longitudinal muscle biopsies as a potential framework for disease monitoring and treatment. The initial feasibility and safety assessment was performed for healthy mice and rats that received two consecutive muscle biopsies. The assessment was performed by utilizing three different tools. Subsequently, the protocol was also applied in leiomyosarcoma tumor-bearing rats. Longitudinal muscle biopsies proved to be a safe and feasible technique, especially in rat models. The application of this protocol to tumor-bearing rats further affirmed its tolerability and feasibility, while microscopic evaluation of the biopsies demonstrated varying levels of muscle atrophy with or without leukocyte infiltration. In this tumor model, sequential muscle biopsies confirmed the variability of the cancer cachexia evolution among subjects and at different time-points. Despite the abundance of promising cancer cachexia data during the past decade, the full potential of muscle biopsies is not being leveraged. Sequential muscle biopsies throughout the disease course represent a feasible and safe tool that can be utilized to guide precision treatment and monitor the response in cancer cachexia research.

Treatment of acquired transthyretin amyloidosis in domino liver transplantation.

BACKGROUND: Domino liver transplantation (DLT) has been commonly used during the last two decades to partly meet the high need for liver transplants. However, the recipients of grafts from patients with noncirrhotic inherited metabolic disorders may ultimately develop metabolic syndrome, and management is usually intricate, being complicated by the underlying initial disorder, other comorbidities, and post-transplantation conditions. CASE: We report here the management and the outcome in a patient with acquired transthyretin amyloidosis after DLT and significant comorbidities. Final treatment with a transthyretin gene silencing agent, patisiran, was well tolerated and resulted in remission of the aggravating neurological deficits in a follow-up period of 2 years. CONCLUSIONS: The case presented here supports the concept that patisiran can target the hepatocytes producing the mutated transthyretin in acquired transthyretin amyloidosis, as efficiently as in hereditary transthyretin amyloidosis (hATTR), and can be used to treat patients with transthyretin amyloidosis after DLT.

A Novel Mutation of the Membrane Metallo-Endopeptidase Gene Related to Late-Onset Hereditary Polyneuropathy: Case Report and Review of the Literature.

The advent of next generation sequencing has revolutionized diagnostic approaches to hereditary polyneuropathies. Recently, mutations on the membrane metallo-endopeptidase (MME) gene, encoding neprilysin, have been related to the development of late-onset Charcot-Marie-Tooth disease type 2 (CMT2). Here, we report the first Greek patient presenting with a slowly progressive late-onset axonal polyneuropathy and a novel, likely pathogenic, heterozygous variant in the MME gene. In addition, we have performed a systematic review of all published case reports of patients with MME mutations. The results of the studies show that MME variants can be inherited as both fully penetrant autosomal-recessive and incompletely penetrant autosomal-dominant traits. A number of heterozygous variants characterized as incompletely penetrant impose an increased risk of developing a CMT2-like phenotype late in life, identical to the case study described here. Greater mutation numbers in different populations and mutation-specific functional studies will be essential to identify the pathogenicity and inheritance of more MME variants.

Variant transthyretin amyloidosis (ATTRv) polyneuropathy in Greece: a broad overview with a focus on non-endemic unexplored regions of the country.

Comprehensive data on variant transthyretin amyloidosis polyneuropathy (ATTRv-PN) in Greece are lacking. We presently provide an overview of ATTRv-PN in Greece, focusing on unexplored non-endemic regions of the country. In total, we identified 57 cases of ATTRv-PN diagnosed over the past 25 years, including 30 from the island of Crete, an apparent endemic region. Patients carried 10 different TTR mutations (C10R; P24S; V30M; R34G; R34T; I68L; A81T; E89Q; E89K and V94A). Carriers of the common V30M mutation constituted 54.3 % of the cohort. A known founder effect for the V30M mutation was present on the island of Crete. Non-endemic cases identified outside the island of Crete are presently reported in more detail. The age of onset ranged from 25 to 77 years, with a mean of 51.1 years. A mean diagnostic delay of 3.2 years was observed. V30M patients had earlier onset and less cardiac involvement than patients carrying other mutations. Genotype-phenotype correlations were largely consistent with published data. We conclude that, with the exception of the Cretan cluster, ATTRv-PN is not endemic in the Greek population. This makes timely diagnosis more challenging, yet absolutely essential given the availability of therapies that can alter the long-term course of the disease.

Trichinosis Imitating an Inflammatory Systematic Disease.

Trichinellosis (trichinosis) is a parasitic infection caused by nematodes of the genus Trichinella. Pigs are the most common source of human infection. We describe a case of a 47-year-old woman presented with a wide range of intermittent symptoms including prolonged fever, dry cough, diarrhea, rash, myalgias and arthralgias. The patient was attended by physicians with various medical specialties such as dermatologists, rheumatologists and allergiologists, but they did not establish a certain diagnosis because of the gradual onset of symptoms, raising the suspicion of a systematic disease. After extensive work up, the diagnosis of trichinosis was established with femoral muscle biopsy compatible with inflammatory myopathy of parasitic etiology with trichinosis to be the predominant diagnosis. Despite the significant delay of diagnosis for almost three months, patient was treated successfully with no further complications. Trichinellosis is a food-borne treatable infection. Preventive measures include community education especially in zones where parasite prevalence is increased, improvement of farming and cooking techniques.

Sjögren Syndrome Associated with Inflammatory Muscle Diseases.

OBJECTIVES: Sjögren's syndrome (SS) is a chronic autoimmune inflammatory disorder characterized by diminished lacrimal and salivary gland function that may affect multiple organ systems. The association of SS with inflammatory myopathies (IM), a group of diseases characterized by chronic inflammation of striated muscle and skin has been infrequently described. METHODS: We present two cases diagnosed with SS who developed IM. We have also conducted a review of the English literature to depict all available clinical evidence on the clinical association of SS with IM. RESULTS: Two female patients diagnosed with SS developed polymyositis (PM) and inclusion body myositis (IBM) respectively. The literature review identified 24 cases with coexistence of the two autoimmune conditions (SS and IM). Twenty-two patients were females and two males. Eight patients were diagnosed with IBM, 15 were diagnosed with PM and 1 with dermatomyositis. All patients had biopsy proven IM. CONCLUSIONS: There is evidence of clinical association of primary SS and IM especially with IBM and PM. Patients with SS and symptoms of muscle weakness should be investigated for associated IM.

Lumbar nerve root avulsions with secondary ipsilateral hip dysplasia in a child.

We report on an 8-year-old child with avulsions of the left L3, L4 and L5 nerve roots and traumatic meningoceles that were not associated with lumbar spine or pelvic girdle fractures. The patient had a history of a road traffic accident. Plain radiographs of the pelvis revealed left hip dysplasia. The magnetic resonance imaging findings of the lumbar spine are illustrated. The pathogenesis of lumbar nerve root avulsions and their association with ipsilateral hip dysplasia are discussed.