How effective is peer-to-peer support in cancer patients and survivors? A systematic review.

PURPOSE: Core components of peer-to-peer (PTP) support for cancer survivors include informational, emotional, and psychosocial aspects. Previous literature on peer support in cancer includes both professionally and peer-led support. Our objective was to summarize studies on the effects of non-professionally led PTP support in cancer. METHODS: We performed a systematic research on studies in PTP support of adult cancer survivors with an interventional design, comparing outcomes of PTP support against any control. We included all studies with a precise definition of a PTP support, published from January 2000 up to March 2023 in peer-reviewed journals in English or German. RESULTS: Out of N = 609 identified publications, we were are able to include n = 18 randomized-controlled trials (RCTs) fulfilling our inclusion criteria. Main settings were dyadic support via telephone, face-to-face (FTF), and web-based online support. Most common outcomes were distress, depressive symptoms, anxiety, and quality of life (QoL). Overall, we found only small effects of PTP support on depression/anxiety, coping, or sexual functioning. Beneficial effects associated with the PTP intervention were apparent in particular in BRCA, in FTF settings, and in assessments of cancer-specific QoL outcomes. CONCLUSION: This review shows that there are a few RCT investigating the effect of PTP support with short-term effects. Overall, there is a need for more RCTs with high methodological standards to evaluate the effectiveness of PTP support.

The COVID-19 Pandemic: Implications for Maternal Mental Health and Early Childhood Development.

Women are particularly susceptible to mental health challenges during the perinatal period. With the onset of the COVID-19 pandemic in 2020, much concern was raised about the impact that the associated isolation, uncertainty, grief, loss and economic upheaval would have on mental health. Women experienced a disproportionate amount of environmental strain during this time, including economic stress and challenges associated with being essential workers; stressors were perhaps most prevalent in communities of color and immigrant groups. For women who were pregnant during the height of the pandemic, it is clear that stress, anxiety, and depression were increased due to changes in medical care and decreases in social support. Increased mental health challenges in the perinatal period have been shown to impact social-emotional, cognitive and behavioral health in infants and children, so the potential consequences of the COVID-19 era are great. This paper discusses these potential impacts and describes important pathways for future research.

Discrepancies between tumor genomic profiling and germline genetic testing.

BACKGROUND: Tumor genomic profiling (TGP) often incidentally identifies germline pathogenic variants (PVs) associated with cancer predisposition syndromes. Methods used by somatic testing laboratories, including germline analysis, differ from designated germline laboratories that have optimized the identification of germline PVs. This study evaluated discrepancies between somatic and germline testing results, and their impact on patients. PATIENTS AND METHODS: Chart reviews were carried out at a single institution for patients who had both somatic and designated germline genetic testing. Cases with discrepant results in which germline PVs were not detected by the somatic laboratory or in which variant classification differed are summarized. RESULTS: TGP was carried out on 2811 cancer patients, 600 of whom also underwent designated germline genetic testing. Germline PVs were identified for 109 individuals. Discrepancies between germline genetic testing and tumor profiling reports were identified in 20 cases, including 14 PVs identified by designated germline genetic testing laboratories that were not reported by somatic testing laboratories and six variants with discrepant classifications between the designated germline and somatic testing laboratories. Three PVs identified by designated germline laboratories are targets for poly adenosine diphosphate-ribose polymerase (PARP) inhibitors and resulted in different treatment options. Of the PVs identified by designated germline laboratories, 60% (n = 12) were in genes with established associations to the patients' cancer, and 40% of the PVs were incidental. The majority (90%) of all discrepant findings, both contributory and incidental, changed management recommendations for these patients, highlighting the importance of comprehensive germline assessment. CONCLUSIONS: Methods used by somatic laboratories, regardless of the inclusion of germline analysis, differ from those of designated germline laboratories for identifying germline PVs. Unrecognized germline PVs may harm patients by missing hereditary syndromes and targeted therapy opportunities (e.g. anti-programmed cell death protein 1 immunotherapy, PARP inhibitors). Clinicians should refer patients who meet the criteria for genetic evaluation regardless of somatic testing outcomes.

Feasibility, pitfalls and results of a structured concept-development phase for a randomized controlled phase III trial on radiotherapy in primary prostate cancer patients.

OBJECTIVE: Failure rate in randomized controlled trials (RCTs) is > 50%, includes safety-problems, underpowered statistics, lack of efficacy, lack of funding or insufficient patient recruitment and is even more pronounced in oncology trials. We present results of a structured concept-development phase (CDP) for a phase III RCT on personalized radiotherapy (RT) in primary prostate cancer (PCa) patients implementing prostate specific membrane antigen targeting positron emission tomography (PSMA-PET). MATERIALS AND METHODS: The 1 yr process of the CDP contained five main working packages: (i) literature search and scoping review, (ii) involvement of individual patients, patients' representatives and patients' self-help groups addressing the patients' willingness to participate in the preparation process and the conduct of RCTs as well as the patient informed consent (PIC), (iii) involvement of national and international experts and expert panels (iv) a phase II pilot study investigating the safety of implementation of PSMA-PET for focal dose escalation RT and (v) in-silico RT planning studies assessing feasibility of envisaged dose regimens and effects of urethral sparing in focal dose escalation. RESULTS: (i) Systematic literature searches confirmed the high clinical relevance for more evidence on advanced RT approaches, in particular stereotactic body RT, in high-risk PCa patients. (ii) Involvement of patients, patient representatives and randomly selected males relevantly changed the PIC and initiated a patient empowerment project for training of bladder preparation. (iii) Discussion with national and international experts led to adaptions of inclusion and exclusion criteria. (iv) Fifty patients were treated in the pilot trial and in- and exclusion criteria as well as enrollment calculations were adapted accordingly. Parallel conduction of the pilot trial revealed pitfalls on practicability and broadened the horizon for translational projects. (v) In-silico planning studies confirmed feasibility of envisaged dose prescription. Despite large prostate- and boost-volumes of up to 66% of the prostate, adherence to stringent anorectal dose constraints was feasible. Urethral sparing increased the therapeutic ratio. CONCLUSION: The dynamic framework of interdisciplinary working programs in CDPs enhances robustness of RCT protocols and may be associated with decreased failure rates. Structured recommendations are warranted to further define the process of such CDPs in radiation oncology trials.

Pilot study of peer modeling with psychological inoculation to promote coronavirus vaccination.

Promoting coronavirus vaccination is deterred by misinformation, ranging from elaborate conspiracy theories about sinister purposes to exaggeration of side effects, largely promulgated by social media. In this pilot study, we tested the effects of different messages on actions leading to vaccination. Two theory-based advertisements were produced for Facebook, which provided video testimonials from peer role models recommending vaccination and its benefits while providing psychological inoculation through the models' acknowledging misinformation, rejecting it and receiving the vaccine. These ads were paid to appear on Facebook users' feeds in rural counties in South Texas, along with a generic vaccine promotion ad from the CDC without peer models or psychological inoculation. Ad viewers could click a link to 'find a vaccine near you'; these responses served as the outcome variable for assessing experimental effects. Ads featuring peer modeling with psychological inoculation yielded a significantly higher rate of positive responses than CDC ads (30.5 versus14.9/1000 people reached in English and 49.7 versus 31.5/1000 in Spanish; P < 0.001 for both English and Spanish rate comparisons). This provides useful pilot data supporting the hypothesis that theory-based communication, i.e. peer modeling with psychological inoculation, may be more effective than more traditional forms of advertising for promoting coronavirus vaccination.

Complete response of advanced cutaneous squamous cell and basal cell carcinomas with sequential cemiplimab and sonidegib therapy.

A 78-year-old woman was referred to our skin cancer centre with three previous incomplete resections in the left cavum conchae of a deep-infiltrating locally advanced, but still asymptomatic basal cell carcinoma (BCC). The patient noted furthermore two rapidly growing exophytic lesions in the left preauricular and cervical area in the last weeks. The clinical and histological distinction of locally advanced from metastatic cutaneous squamous cell carcinoma (CSCC) lesions was challenging. Imaging analysis with CT scans showed, however, an involvement of the parotid gland as well as multiple small lymph node metastases. The interdisciplinary tumour board decision at our institution recommended a systemic treatment with the PD1-antibody cemiplimab. After 13 cycles with cemiplimab at a dose of 350 mg intravenously every 3-weeks, the patient showed a complete response of the two CSCC lesions with histological confirmation. However, the BCC of the left ear appeared to be unchanged and still asymptomatic. The interdisciplinary tumour board considered this tumour to be no candidate for a curative resection or irradiation. Therefore, the patient was exposed to the hedgehog inhibitor sonidegib with a conventional dose of 200 mg orally per day. After 3 months of treatment, the tumour showed a markable regression and a complete response was confirmed by 3-punch biopsies from this preoperated lesion. Both cemiplimab and sonidegib were excellently tolerated with almost no adverse events apart from a mild fatigue (CTC grade 1) over the first 3 weeks of the cemiplimab therapy. There were no laboratory abnormalities found.

[COVID-19 and the central and peripheral nervous system]. / COVID-19: Auswirkungen auf das zentrale und periphere Nervensystem.

The health effects of coronavirus disease 2019 (COVID-19) caused by the infection of SARS-CoV­2 (severe acute respiratory syndrome coronavirus 2) are becoming increasingly clear as the pandemic spreads. In addition to the lungs, other organs are also affected, which can significantly influence morbidity and mortality. In particular, neurological symptoms involving the central nervous system can lead to acute or long-term consequences. The mechanisms of this neuropathogenesis of SARS-CoV­2 infection and its relation to acute and chronic neurological symptoms are the subject of current studies investigating a potential direct and indirect viral infection of the nervous system. The following review summarizes the current status of neuropathological manifestations, molecular pathogenesis, possible infection pathways in the nervous system, and systemic effects. In addition, an overview of the Germany-wide CNS-COVID19 registry and collaborations is presented, which should contribute to a better understanding of the neurological symptoms of COVID-19.

An international update of the EORTC questionnaire for assessing quality of life in breast cancer patients: EORTC QLQ-BR45.

BACKGROUND: The European Organization for Research and Treatment of Cancer (EORTC) QLQ-BR23 was one of the first disease-specific questionnaires developed in 1996 to assess quality of life (QoL) in patients with breast cancer (BC). However, since 1996 major changes in BC treatment have occurred, requiring an update of the EORTC BC module. This study presents the results of the phase I-III update of the QLQ-BR23 questionnaire. PATIENTS AND METHODS: The update of the EORTC QLQ-BR23 module followed standard EORTC guidelines. A systematic literature review revealed 83 potential relevant QoL issues during phases I and II. After shortening the issues list and following interviews with patients and health care providers, 15 relevant issues were transformed into 27 items. The preliminary module was pretested in an international, multicentre phase III study to identify and solve potential problems with wording comprehensibility and acceptability of the items. Descriptive statistics are provided. Analyses were qualitative and quantitative. We provide a psychometric structure of the items. RESULTS: The phase I and II results indicated the need to supplement the original QLQ-BR23 with additional items related to newer therapeutic options. The phase III study recruited a total of 250 patients (from 12 countries). The final updated phase III module contains a total of 45 items: 23 items from the QLQ-BR23 and 22 new items. The new items contain two multi-item scales: a target symptom scale and a satisfaction scale. The target symptom scale can be divided into three subscales: endocrine therapy, endocrine sexual and skin/mucosa scale. CONCLUSION: Our work has led to the development of a new EORTC QLQ-BR45 module that provides a more accurate and comprehensive assessment of the impact of new and scalable treatments on patients' QoL. The final version of the EORTC QLQ-BR45 is currently available for use in clinical practice. The final phase IV study is underway to confirm psychometric properties of the module.

An integrative correlation of myopathology, phenotype and genotype in late onset Pompe disease.

AIMS: Pompe disease is caused by pathogenic mutations in the alpha 1,4-glucosidase (GAA) gene and in patients with late onset Pome disease (LOPD), genotype-phenotype correlations are unpredictable. Skeletal muscle pathology includes glycogen accumulation and altered autophagy of various degrees. A correlation of the muscle morphology with clinical features and the genetic background in GAA may contribute to the understanding of the phenotypic variability. METHODS: Muscle biopsies taken before enzyme replacement therapy were analysed from 53 patients with LOPD. On resin sections, glycogen accumulation, fibrosis, autophagic vacuoles and the degree of muscle damage (morphology-score) were analysed and the results were compared with clinical findings. Additional autophagy markers microtubule-associated protein 1A/1B-light chain 3, p62 and Bcl2-associated athanogene 3 were analysed on cryosections from 22 LOPD biopsies. RESULTS: The myopathology showed a high variability with, in most patients, a moderate glycogen accumulation and a low morphology-score. High morphology-scores were associated with increased fibrosis and autophagy highlighting the role of autophagy in severe stages of skeletal muscle damage. The morphology-score did not correlate with the patient's age at biopsy, disease duration, nor with the residual GAA enzyme activity or creatine-kinase levels. In 37 patients with LOPD, genetic analysis identified the most frequent mutation, c.-32-13T>G, in 95%, most commonly in combination with c.525delT (19%). No significant correlation was found between the different GAA genotypes and muscle morphology type. CONCLUSIONS: Muscle morphology in LOPD patients shows a high variability with, in most cases, moderate pathology. Increased pathology is associated with more fibrosis and autophagy.

Outcomes and outcome measures used in evaluation of communication training in oncology - a systematic literature review, an expert workshop, and recommendations for future research.

BACKGROUND: Communication between health care provider and patients in oncology presents challenges. Communication skills training have been frequently developed to address those. Given the complexity of communication training, the choice of outcomes and outcome measures to assess its effectiveness is important. The aim of this paper is to 1) perform a systematic review on outcomes and outcome measures used in evaluations of communication training, 2) discuss specific challenges and 3) provide recommendations for the selection of outcomes in future studies. METHODS: To identify studies and reviews reporting on the evaluation of communication training for health care professionals in oncology, we searched seven databases (Ovid MEDLINE, CENTRAL, CINAHL, EMBASE, PsychINFO, PsychARTICLES and Web of Science). We extracted outcomes assessed and the respective assessment methods. We held a two-day workshop with experts (n = 16) in communication theory, development and evaluation of generic or cancer-specific communication training and/or outcome measure development to identify and address challenges in the evaluation of communication training in oncology. After the workshop, participants contributed to the development of recommendations addressing those challenges. RESULTS: Out of 2181 references, we included 96 publications (33 RCTs, 2 RCT protocols, 4 controlled trials, 36 uncontrolled studies, 21 reviews) in the review. Most frequently used outcomes were participants' training evaluation, their communication confidence, observed communication skills and patients' overall satisfaction and anxiety. Outcomes were assessed using questionnaires for participants (57.3%), patients (36.0%) and observations of real (34.7%) and simulated (30.7%) patient encounters. Outcomes and outcome measures varied widely across studies. Experts agreed that outcomes need to be precisely defined and linked with explicit learning objectives of the training. Furthermore, outcomes should be assessed as broadly as possible on different levels (health care professional, patient and interaction level). CONCLUSIONS: Measuring the effects of training programmes aimed at improving health care professionals' communication skills presents considerable challenges. Outcomes as well as outcome measures differ widely across studies. We recommended to link outcome assessment to specific learning objectives and to assess outcomes as broadly as possible.

Mesh migration following abdominal hernia repair: a comprehensive review.

PURPOSE: This study reviewed the literature regarding mesh migration in abdominal hernia repair. The aim of this study is to interrogate incidence, common type of abdominal hernia repair leading to migration, patterns of mesh migration, and materials associated with migration. METHODS: A comprehensive literature review was conducted. PubMed and MEDLINE were searched for relevant articles in the English literature. We employed Ovid syntax from 1949 to January 2010, the Cochrane Library, Google and Google Scholar. The clinical trial database Clinicaltrials.gov was reviewed. Letters to the editor were reviewed to extract cross-references. Multiple keywords were used alone and in combination to extract all relevant articles. RESULTS: In total, 287 unique English citations were reviewed. Of these, 84 articles were selected and consisted of 3 case series, 77 case reports, 2 literature reviews, 1 retrospective study, and 1 prospective, observational study. In an analysis of available cases, the average age was 59.8 ± 13.8 years with a male predominance (76.2%). The index hernia repair was inguinal in 62.9%, incisional/ventral in 28.1%, umbilical in 6.7%, and other in 2.2%. Within the inguinal hernia group, 51.8% were open repairs, 42.9% were laparoscopic, and 1.8% were robotic. Implicated mesh materials included polypropylene, PTFE, and composite mesh. Migration commonly affected multiple organs (31.5%). CONCLUSIONS: It is likely that more cases of mesh migration will appear in the literature. Reports are heterogeneous and highlight the diversity of this complication. A standardized method of reporting is needed to develop guidelines and recommendations for this presentation.

Targeting myelin lipid metabolism as a potential therapeutic strategy in a model of CMT1A neuropathy.

In patients with Charcot-Marie-Tooth disease 1A (CMT1A), peripheral nerves display aberrant myelination during postnatal development, followed by slowly progressive demyelination and axonal loss during adult life. Here, we show that myelinating Schwann cells in a rat model of CMT1A exhibit a developmental defect that includes reduced transcription of genes required for myelin lipid biosynthesis. Consequently, lipid incorporation into myelin is reduced, leading to an overall distorted stoichiometry of myelin proteins and lipids with ultrastructural changes of the myelin sheath. Substitution of phosphatidylcholine and phosphatidylethanolamine in the diet is sufficient to overcome the myelination deficit of affected Schwann cells in vivo. This treatment rescues the number of myelinated axons in the peripheral nerves of the CMT rats and leads to a marked amelioration of neuropathic symptoms. We propose that lipid supplementation is an easily translatable potential therapeutic approach in CMT1A and possibly other dysmyelinating neuropathies.

Novel SBF2 mutations and clinical spectrum of Charcot-Marie-Tooth neuropathy type 4B2.

Biallelic SBF2 mutations cause Charcot-Marie-Tooth disease type 4B2 (CMT4B2), a sensorimotor neuropathy with autosomal recessive inheritance and association with glaucoma. Since the discovery of the gene mutation, only few additional patients have been reported. We identified seven CMT4B2 families with nine different SBF2 mutations. Revisiting genetic and clinical data from our cohort and the literature, SBF2 variants were private mutations, including exon-deletion and de novo variants. The neuropathy typically started in the first decade after normal early motor development, was predominantly motor and had a rather moderate course. Electrophysiology and nerve biopsies indicated demyelination and excess myelin outfoldings constituted a characteristic feature. While neuropathy was >90% penetrant at age 10 years, glaucoma was absent in ~40% of cases but sometimes developed with age. Consequently, SBF2 mutation analysis should not be restricted to individuals with coincident neuropathy and glaucoma, and CMT4B2 patients without glaucoma should be followed for increased intraocular pressure. The presence of exon-deletion and de novo mutations demands comprehensive mutation scanning and family studies to ensure appropriate diagnostic approaches and genetic counseling.

Expression profile of pattern recognition receptors in skeletal muscle of SOD1(G93A) amyotrophic lateral sclerosis (ALS) mice and sporadic ALS patients.

AIMS: Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motoneurons and progressive muscle wasting. Inflammatory processes, mediated by non-neuronal cells, such as glial cells, are known to contribute to disease progression. Inflammasomes consist of pattern recognition receptors (PRRs), apoptosis-associated speck-like protein (ASC) and caspase 1 and are essential for interleukin (IL) processing and a rapid immune response after tissue damage. Recently, we described inflammasome activation in the spinal cord of ALS patients and in SOD1(G93A) ALS mice. Since pathological changes in the skeletal muscle are early events in ALS, we hypothesized that PRRs might be abnormally expressed in muscle fibre degeneration. METHODS: Western blot analysis, real-time PCR and immunohistochemistry were performed with muscle tissue from presymptomatic and early-symptomatic male SOD1(G93A) mice and with muscle biopsies of control and sporadic ALS (sALS) patients. Analysed PRRs include nucleotide-binding oligomerization domain-like (NOD-like) receptor protein 1 (NLRP1), NLR protein 3 (NLRP3), NLR family CARD domain-containing 4 (NLRC4) and absent in melanoma 2. Additionally, expression levels of ASC, caspase 1, interleukin 1 beta (IL1ß) and interleukin 18 (IL18) were evaluated. RESULTS: Expression of PRRs and ASC was detected in murine and human tissue. The PRR NLRC4, caspase 1 and IL1ß were significantly elevated in denervated muscle of SOD1(G93A) mice and sALS patients. Furthermore, levels of caspase 1 and IL1ß were already increased in presymptomatic animals. CONCLUSION: Our findings suggest that increased inflammasome activation may be involved in skeletal muscle pathology in ALS. Furthermore, elevated levels of NLRC4, caspase 1 and IL1ß reflect early changes in the skeletal muscle and may contribute to the denervation process.

One in two cancer patients is significantly distressed: Prevalence and indicators of distress.

OBJECTIVE: Psychological distress is common in cancer patients, and awareness of its indicators is essential. We aimed to assess the prevalence of psychological distress and to identify problems indicative of high distress. METHODS: We used the distress thermometer (DT) and its 34-item problem list to measure psychological distress in 3724 cancer patients (mean age 58 years; 57% women) across major tumor entities, enrolled in an epidemiological multicenter study. To identify distress-related problems, we conducted monothetic analyses. RESULTS: We found high levels of psychological distress (DT ≥ 5) in 52% of patients. The most prevalent problems were fatigue (56%), sleep problems (51%), and problems getting around (47%). Sadness, fatigue, and sleep problems were most strongly associated with the presence of other problems. High distress was present in 81.4% of patients reporting all 3 of these problems (DT M = 6.4). When analyzing only the subset of physical problems, fatigue, problems getting around, and indigestion showed the strongest association with the remaining problems and 76.3% of patients with all 3 problems were highly distressed (DT M = 6.1). CONCLUSIONS: Our results show a high prevalence of psychological distress in cancer patients, as well as a set of problems that indicate the likely presence of other problems and high distress and can help clinicians identify distressed patients even if no routine distress screening is available.

[The Development of Quality Standards for the Psychosocial Outpatient Care of Cancer Patients - Results of a Delphi Survey]. / Die Entwicklung von Qualitätsstandards für die ambulante psychosoziale Krebsberatung ­ Ergebnisse einer Delphibefragung.

BACKGROUND: The psychosocial outpatient care of cancer patients and their families is a central element of oncological care. To date, the provision of care to this group is very heterogeneous in terms of the spectrum of services offered and quality of care. The aim of this study was to develop a multidimensional classification of quality standards for psychosocial outpatient cancer counseling. METHOD: We conducted a study using the Delphi method. 97 experts from more than 10 different fields of action or institutional contexts (e. g. mental health care professionals, cancer societies, self-help groups) were included in 3 rounds of Delphi assessment. Finally, 134 single criteria within 9 quality areas (e. g. staff, range of services, documentation) were generated and evaluated for their relevance, clarity, comprehensiveness and level of obligation. RESULT: A total of 119 individual criteria (88.8%) achieved consensus within the 3 Delphi rounds. Hereof, 94 were basic criteria (79%) and 25 optional criteria (21%). The highest number of individual criteria referred to the service spectrum (26 individual criteria), documentation (21) as well as staff and accessibility (16 each). Fifteen criteria (11.2%) achieved no consensus and were removed. CONCLUSION: For the first time, criteria for assessing the quality of psychosocial outpatient cancer counseling with expert consensus are available, facilitating the evaluation of psychosocial outpatient cancer counseling.

ALS-Associated Endoplasmic Reticulum Proteins in Denervated Skeletal Muscle: Implications for Motor Neuron Disease Pathology.

Alpha-motoneurons and muscle fibres are structurally and functionally interdependent. Both cell types particularly rely on endoplasmic reticulum (ER/SR) functions. Mutations of the ER proteins VAPB, SigR1 and HSP27 lead to hereditary motor neuron diseases (MNDs). Here, we determined the expression profile and localization of these ER proteins/chaperons by immunohistochemistry and immunoblotting in biopsy and autopsy muscle tissue of patients with amyotrophic lateral sclerosis (ALS) and other neurogenic muscular atrophies (NMAs) and compared these patterns to mouse models of neurogenic muscular atrophy. Postsynaptic neuromuscular junction staining for VAPB was intense in normal human and mouse muscle and decreased in denervated Nmd2J mouse muscle fibres. In contrast, VAPB levels together with other chaperones and autophagy markers were increased in extrasynaptic regions of denervated muscle fibres of patients with MNDs and other NMAs, especially at sites of focal myofibrillar disintegration (targets). These findings did not differ between NMAs due to ALS and other causes. G93A-SOD1 mouse muscle fibres showed a similar pattern of protein level increases in denervated muscle fibres. In addition, they showed globular VAPB-immunoreactive structures together with misfolded SOD1 protein accumulations, suggesting a primary myopathic change. Our findings indicate that altered expression and localization of these ER proteins and autophagy markers are part of the dynamic response of muscle fibres to denervation. The ER is particularly prominent and vulnerable in both muscle fibres and alpha-motoneurons. Thus, ER pathology could contribute to the selective build-up of degenerative changes in the neuromuscular axis in MNDs.