Beriberi following sleeve gastrectomy.

Bariatric surgery is being undertaken more frequently in response to rising levels of obesity but is increasingly also requested as a cosmetic choice. Nutritional deficiencies are a recognised consequence of gastrectomy, with potentially severe and permanent neurological sequelae. We present two cases of acute, severe polyneuropathy following sleeve gastrectomy. Severe thiamine deficiency was considered in both cases but with delayed proof and a significant initial differential diagnosis. Neurologists must have a high index of suspicion for the peripheral as well as central presentations of thiamine deficiency to avoid permanent disability. We also call for explicit information resources warning of the risk and signs of thiamine deficiency to be provided routinely to patients after gastrectomy.

Towards smart and sustainable development of modern berry cultivars in Europe.

Fresh berries are a popular and important component of the human diet. The demand for high-quality berries and sustainable production methods is increasing globally, challenging breeders to develop modern berry cultivars that fulfill all desired characteristics. Since 1994, research projects have characterized genetic resources, developed modern tools for high-throughput screening, and published data in publicly available repositories. However, the key findings of different disciplines are rarely linked together, and only a limited range of traits and genotypes has been investigated. The Horizon2020 project BreedingValue will address these challenges by studying a broader panel of strawberry, raspberry and blueberry genotypes in detail, in order to recover the lost genetic diversity that has limited the aroma and flavor intensity of recent cultivars. We will combine metabolic analysis with sensory panel tests and surveys to identify the key components of taste, flavor and aroma in berries across Europe, leading to a high-resolution map of quality requirements for future berry cultivars. Traits linked to berry yields and the effect of environmental stress will be investigated using modern image analysis methods and modeling. We will also use genetic analysis to determine the genetic basis of complex traits for the development and optimization of modern breeding technologies, such as molecular marker arrays, genomic selection and genome-wide association studies. Finally, the results, raw data and metadata will be made publicly available on the open platform Germinate in order to meet FAIR data principles and provide the basis for sustainable research in the future.

Autophagy in non-immune-mediated rhabdomyolysis: Assessment of p62 immunohistochemistry.

INTRODUCTION/AIMS: p62 immunochemistry (IHC) has been shown to aid diagnosis with distinct patterns of muscle fiber staining observed in some inflammatory, hereditary, and degenerative myopathies, such as immune-mediated necrotizing myopathy (IMNM). The pattern of p62 staining may help narrow the pathological differential diagnosis of rhabdomyolysis. However, there is a lack of information on the pattern of p62 IHC in non-immune-mediated rhabdomyolysis. In this study we aim to describe histopathological findings in non-immune-mediated rhabdomyolysis, with particular emphasis on the pattern of p62 IHC. METHODS: We retrospectively reviewed the histopathological features of patients with a confirmed diagnoses of non-immune-mediated rhabdomyolysis referred to our center. RESULTS: Five patients were identified. Rhabdomyolysis was determined to be due to statin-associated toxicity in three patients, alcohol overuse in one patient, and intensive exercise in one patient. All patients showed increased numbers of necrotic and regenerating muscle fibers. Diffuse and finely granular sarcoplasmic positive p62 staining was present in scattered non-necrotic muscle fibers in all patients. DISCUSSION: Disturbance of autophagy appears to be a common mechanism in non-immune-mediated rhabdomyolysis. Our results show p62 IHC is sensitive but lacks specificity. Therefore, the pattern of p62 staining does not distinguish non-immune-mediated rhabdomyolysis from histopathologically similar IMNM.

Utilising clinical parameters to improve the selection of nerve biopsy candidates.

BACKGROUND: Peripheral nerve biopsy is a valuable final diagnostic tool; however, histopathological results can be non-diagnostic. AIMS: We aim to identify quality improvement measures by evaluating the pre-biopsy assessment and diagnostic yield of specific histopathological diagnosis. METHODS: This was a retrospective study based on 10 years of experience with peripheral nerve biopsies at a single centre. Clinical data were obtained regarding pre-biopsy history, examination, serum and cerebrospinal fluid (CSF) investigations, neurophysiology and peripheral nerve imaging. Based upon a histopathological outcome, patients were grouped into vasculitis, granulomatous and infiltrative (diagnostic) group, or a comparison group of non-specific axonal neuropathy and normal (non-specific/normal) group. RESULTS: From a cohort of 64 patients, 21 (32.8%) were included in the diagnostic group and 30 (46.9%) in the non-specific/normal group. Clinical parameters associated with the diagnostic group were shorter history (mean 10.2 months vs 38.1), stepwise progression (81% vs 20%), neuropathic pain (85.7% vs 56.7%), vasculitic rash (23.8% vs 0%), mononeuritis multiplex (57.1% vs 10%), asymmetry (90.5% vs 60%), raised white cell count (47.6% vs 16.7%), myeloperoxidase antibody (19.1% vs 0%) and abnormal peripheral nerve imaging (33.3% vs 10%). CONCLUSION: Selection of patients undergoing nerve biopsy requires careful consideration of clinical parameters, including peripheral nerve imaging. Several quality improvement measures are proposed to improve yield of clinically actionable information from nerve biopsy.

Metastatic meningioma: a case series and systematic review.

BACKGROUND: Meningiomas are the most common primary intracranial tumor. While the majority of meningiomas are benign, rarely they can metastasize extracranially. There is a need for a more comprehensive review of these patients to improve our understanding of this rare phenomenon and its prevalence globally. Here we describe our institution's experience of patients presenting with metastatic meningiomas. We further perform a systematic review of the existing literature to explore common features of this rare manifestation of meningioma and review the efficacy of current treatments. METHODS: We performed a retrospective clinical review of all adult patients with metastatic meningioma managed at our institution over the past 20 years, identifying 6 patients. We then performed a systematic review of cases of metastatic meningioma in the literature ranging from the years 1886 to 2022. A descriptive analysis was then conducted on the available data from 1979 onward, focusing on the grade and location of the primary tumor as well as the latency period to, and location of, the metastasis. RESULTS: In total, we analyzed 155 cases. Fifty-four percent of patients initially presented with a primary meningioma located in the convexity. The most common site of metastasis was the lung. Risk factors associated with a shorter time to metastasis were male sex and a high initial grade of the tumor. Regarding treatment, the addition of chemotherapy was the most common adjunct to the standard management of surgery and radiotherapy. Despite an exhaustive review we were unable to identify effective treatments. The majority of published cases came from centers situated in high-income countries (84%) while only 16% came from lower- and middle-income countries. CONCLUSIONS: Metastatic meningiomas pose a pertinent, and likely underestimated, clinical challenge within modern neurosurgery. To optimize management, timely identification of these patients is important. More research is needed to explore the mechanisms underlying these tumors to better guide the development of effective screening and management protocols. However, screening of each meningioma patient is not feasible, and at the heart of this challenge is the inability to control the primary disease. Ultimately, a consensus is needed as to how to correctly screen for and manage these patients; genomic and epigenomic approaches could hold the answer to finding druggable targets.

AL amyloidosis presenting with isolated lumbosacral radiculoplexus neuropathy.

A 45-year-old man presented with an isolated sciatic mononeuropathy, which then evolved into a lumbosacral radiculoplexus neuropathy. His initial symptoms included lower limb pain, sensory disturbance and later weakness, without autonomic dysfunction. Neurophysiology suggested a postganglionic neuropathy. MR and ultrasound scans of the thighs showed right sciatic nerve thickening, and CSF analysis showed albuminocytological dissociation. Fluorodeoxyglucose positron emission tomography (FDG PET) was unremarkable. He then developed orthostatic symptoms and urinary disturbance, and was found to have an IgM paraprotein. Fat aspirate, cardiac and whole-body imaging found no amyloid deposition, and genetic testing for transthyretin amyloidosis was negative. A bone marrow biopsy was unremarkable. However, neuropathology review of a proximal, fascicular nerve biopsy identified a lambda chain-restricted plasma cell population with positive Congo red staining, leading to a diagnosis of peripheral nerve restricted amyloid light amyloidosis. We discuss the diagnostic approach to this case from the perspectives of neurology, neurophysiology, radiology and neuropathology.

Leucine-Rich Glioma-Inactivated 1 versus Contactin-Associated Protein-like 2 Antibody Neuropathic Pain: Clinical and Biological Comparisons.

Pain is a under-recognized association of leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) antibodies. Of 147 patients with these autoantibodies, pain was experienced by 17 of 33 (52%) with CASPR2- versus 20 of 108 (19%) with LGI1 antibodies (p = 0.0005), and identified as neuropathic in 89% versus 58% of these, respectively. Typically, in both cohorts, normal nerve conduction studies and reduced intraepidermal nerve fiber densities were observed in the sampled patient subsets. In LGI1 antibody patients, pain responded to immunotherapy (p = 0.008), often rapidly, with greater residual patient-rated impairment observed in CASPR2 antibody patients (p = 0.019). Serum CASPR2 antibodies, but not LGI1 antibodies, bound in vitro to unmyelinated human sensory neurons and rodent dorsal root ganglia, suggesting pathophysiological differences that may underlie our clinical observations. ANN NEUROL 2021;90:683-690.

Acute small fiber neuropathy after Oxford-AstraZeneca ChAdOx1-S vaccination: A report of three cases and review of the literature.

Small fiber neuropathy usually presents with gradual and progressive chronic length-dependent pain. Acute small fiber neuropathy is rarely reported. Three patients with acute onset neuropathic pain after Oxford-AstraZeneca ChAdOx1-S vaccination are described. Two patients were identified at the Oxford University NHS Foundation Trust, Oxford, UK and one patient in Red de Salud UC Christus, Santiago, Chile. All patients underwent a clinical assessment that included a detailed neurological examination, laboratory investigations, nerve conduction studies, thermal threshold testing, and skin biopsy for intra-epidermal nerve fiber density. Patients seen in Oxford underwent MRI of the brain and spinal cord. Cerebrospinal analysis was not performed. Neuropathic symptoms (burning pain, dysaesthesias) developed in the hands and feet within 2 weeks of vaccination. On clinical examination, there was pinprick and thermal hyposensitivity in the area of neuropathic pain. Laboratory investigation, nerve conduction tests, sympathetic skin responses, and MRI showed no relevant abnormalities. Thermal thresholds were abnormal and intra-epidermal nerve fiber density in the lower leg was reduced. In two cases symptoms persist after several months. Three cases of definite acute small fiber neuropathy after Oxford-AstraZeneca ChAdOx1-S vaccination are described. At follow up, neuropathic pain was present in two of the patients.

Recent advances in the biology of tumour hypoxia with relevance to diagnostic practice and tissue-based research.

In this review article, we examine the importance of low levels of oxygen (hypoxia) in cancer biology. We provide a brief description of how mammalian cells sense oxygen. The hypoxia-inducible factor (HIF) pathway is currently the best characterised oxygen-sensing system, but recent work has revealed that mammals also use an oxygen-sensing system found in plants to regulate the abundance of some proteins and peptides with an amino-terminal cysteine residue. We discuss how the HIF pathway is affected during the growth of solid tumours, which develop in microenvironments with gradients of oxygen availability. We then introduce the concept of 'pseudohypoxia', a state of constitutive, oxygen-independent HIF system activation that occurs due to oncogenic stimulation in a number of specific tumour types that are of immediate relevance to diagnostic histopathologists. We provide an overview of the different methods of quantifying tumour hypoxia, emphasising the importance of pre-analytic factors in interpreting the results of tissue-based studies. Finally, we review recent approaches to targeting hypoxia/HIF system activation for therapeutic benefit, the application of which may require knowledge of which hypoxia signalling components are being utilised by a given tumour. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

The clinical spectrum of the congenital myasthenic syndrome resulting from COL13A1 mutations.

Next generation sequencing techniques were recently used to show mutations in COL13A1 cause synaptic basal lamina-associated congenital myasthenic syndrome type 19. Animal studies showed COL13A1, a synaptic extracellular-matrix protein, is involved in the formation and maintenance of the neuromuscular synapse that appears independent of the Agrin-LRP4-MuSK-DOK7 acetylcholine receptor clustering pathway. Here, we report the phenotypic spectrum of 16 patients from 11 kinships harbouring homozygous or heteroallelic mutations in COL13A1. Clinical presentation was mostly at birth with hypotonia and breathing and feeding difficulties often requiring ventilation and artificial feeding. Respiratory crisis related to recurrent apnoeas, sometimes triggered by chest infections, were common early in life but resolved over time. The predominant pattern of muscle weakness included bilateral ptosis (non-fatigable in adulthood), myopathic facies and marked axial weakness, especially of neck flexion, while limb muscles were less involved. Other features included facial dysmorphism, skeletal abnormalities and mild learning difficulties. All patients tested had results consistent with abnormal neuromuscular transmission. Muscle biopsies were within normal limits or showed non-specific changes. Muscle MRI and serum creatine kinase levels were normal. In keeping with COL13A1 mutations affecting both synaptic structure and presynaptic function, treatment with 3,4-diaminopyridine and salbutamol resulted in motor and respiratory function improvement. In non-treated cases, disease severity and muscle strength improved gradually over time and several adults recovered normal muscle strength in the limbs. In summary, patients with COL13A1 mutations present mostly with severe early-onset myasthenic syndrome with feeding and breathing difficulties. Axial weakness is greater than limb weakness. Disease course improves gradually over time, which could be consistent with the less prominent role of COL13A1 once the neuromuscular junction is mature. This report emphasizes the role of collagens at the human muscle endplate and should facilitate the recognition of this disorder, which can benefit from pharmacological treatment.

CLIPPERS: A case report with radiology, three serial biopsies and a literature review.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare central nervous system inflammatory disorder primarily affecting the brainstem and cerebellum. We report a case of CLIPPERS in a 45-year-old man presenting with left facial numbness and dizziness. Imaging studies were conducted repeatedly over an 8-year follow-up period. Given diagnostic uncertainty in the early stages of the disease, three serial biopsies were obtained, which together with the clinical and radiological findings, led to the diagnosis. This case highlights the diagnostic challenges regarding the rare entity of CLIPPERS and discusses the main differential diagnoses that are necessary to consider. Additionally, some of the atypical features of this case, including the presenting finding of a large, solidly enhancing lesion on radiological imaging and prominent plasma cells on pathology, contribute to expanding the spectrum of appearances for CLIPPERS.

Retrospective natural history of thymidine kinase 2 deficiency.

BACKGROUND: Thymine kinase 2 (TK2) is a mitochondrial matrix protein encoded in nuclear DNA and phosphorylates the pyrimidine nucleosides: thymidine and deoxycytidine. Autosomal recessive TK2 mutations cause a spectrum of disease from infantile onset to adult onset manifesting primarily as myopathy. OBJECTIVE: To perform a retrospective natural history study of a large cohort of patients with TK2 deficiency. METHODS: The study was conducted by 42 investigators across 31 academic medical centres. RESULTS: We identified 92 patients with genetically confirmed diagnoses of TK2 deficiency: 67 from literature review and 25 unreported cases. Based on clinical and molecular genetics findings, we recognised three phenotypes with divergent survival: (1) infantile-onset myopathy (42.4%) with severe mitochondrial DNA (mtDNA) depletion, frequent neurological involvement and rapid progression to early mortality (median post-onset survival (POS) 1.00, CI 0.58 to 2.33 years); (2) childhood-onset myopathy (40.2%) with mtDNA depletion, moderate-to-severe progression of generalised weakness and median POS at least 13 years; and (3) late-onset myopathy (17.4%) with mild limb weakness at onset and slow progression to respiratory insufficiency with median POS of 23 years. Ophthalmoparesis and facial weakness are frequent in adults. Muscle biopsies show multiple mtDNA deletions often with mtDNA depletion. CONCLUSIONS: In TK2 deficiency, age at onset, rate of weakness progression and POS are important variables that define three clinical subtypes. Nervous system involvement often complicates the clinical course of the infantile-onset form while extraocular muscle and facial involvement are characteristic of the late-onset form. Our observations provide essential information for planning future clinical trials in this disorder.

More than meets the MRI: case report of a carcinoid tumour metastasis mimicking a meningioma.

Cerebral metastases from carcinoid tumours are rarely reported and confer a much poorer prognosis than carcinoid metastases elsewhere in the body. We describe a case of carcinoid brain metastasis closely resembling a meningioma on magnetic resonance imaging (MRI), and review current treatment options.

Autoimmune necrotising myopathy and HMGCR antibodies.

Statins lower serum cholesterol concentrations by inhibiting the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). Muscle side effects are relatively common and include asymptomatic elevation of serum creatine kinase (CK), myalgia, proximal muscle weakness and rhabdomyolysis. More recently, a subset of cases of immune-mediated necrotising myopathy has been found to have antibodies against HMGCR. It is often an aggressive and debilitating myopathy and has a complex pathogenesis characterised by fibre necrosis, usually with minimal associated inflammation. Not all such patients are taking statins. The general consensus is that best treatment involves withdrawing the statin and giving immunosuppressive and immunomodulatory treatment. We describe three cases of HMGCR-related immune-mediated necrotising myopathy, detailing their clinical course and subsequent management, illustrating the spectrum of this disorder.

Aging-related tau astrogliopathy (ARTAG): harmonized evaluation strategy.

Pathological accumulation of abnormally phosphorylated tau protein in astrocytes is a frequent, but poorly characterized feature of the aging brain. Its etiology is uncertain, but its presence is sufficiently ubiquitous to merit further characterization and classification, which may stimulate clinicopathological studies and research into its pathobiology. This paper aims to harmonize evaluation and nomenclature of aging-related tau astrogliopathy (ARTAG), a term that refers to a morphological spectrum of astroglial pathology detected by tau immunohistochemistry, especially with phosphorylation-dependent and 4R isoform-specific antibodies. ARTAG occurs mainly, but not exclusively, in individuals over 60 years of age. Tau-immunoreactive astrocytes in ARTAG include thorn-shaped astrocytes at the glia limitans and in white matter, as well as solitary or clustered astrocytes with perinuclear cytoplasmic tau immunoreactivity that extends into the astroglial processes as fine fibrillar or granular immunopositivity, typically in gray matter. Various forms of ARTAG may coexist in the same brain and might reflect different pathogenic processes. Based on morphology and anatomical distribution, ARTAG can be distinguished from primary tauopathies, but may be concurrent with primary tauopathies or other disorders. We recommend four steps for evaluation of ARTAG: (1) identification of five types based on the location of either morphologies of tau astrogliopathy: subpial, subependymal, perivascular, white matter, gray matter; (2) documentation of the regional involvement: medial temporal lobe, lobar (frontal, parietal, occipital, lateral temporal), subcortical, brainstem; (3) documentation of the severity of tau astrogliopathy; and (4) description of subregional involvement. Some types of ARTAG may underlie neurological symptoms; however, the clinical significance of ARTAG is currently uncertain and awaits further studies. The goal of this proposal is to raise awareness of astroglial tau pathology in the aged brain, facilitating communication among neuropathologists and researchers, and informing interpretation of clinical biomarkers and imaging studies that focus on tau-related indicators.

Chordoid glioma of the third ventricle: a patient presenting with SIADH and a review of this rare tumor.

INTRODUCTION: Chordoid glioma of the third ventricle is a rare and recently described tumor characterized by a unique histomorphology and exclusive association with the suprasellar/third ventricular compartment. Its clinical, radiological and histological features may vary. Despite the fact that chordoid glioma is a low-grade tumor, its prognosis has been relatively poor because of its insidious presentation and the difficulty in obtaining complete surgical resection. MATERIALS AND METHODS: Here, we report on a new case of chordoid glioma occurring in a 48-year-old woman, presented with hyponatremia, and on the initial work-up with a diagnosis of hyponatremia due at least in part to SIADH. We review the current literature on this rare pathology, discuss the radiological and histopathologic findings, and discuss the optimal management of chordoid glioma in general. CONCLUSION: Based on this new case and the previous literature reports, we suggest that chordoid glioma should be included in the differential diagnosis of uncommon masses of the third ventricle, especially in middle-aged women, and we emphasize current management guidelines.

Cryopreservation of in vitro shoot tips of strawberry by the vitrification method - establishment of a duplicate collection of Fragaria germplasm.

BACKGROUND: The National German Strawberry Genebank, which includes 183 cultivars and 270 accessions of wild Fragaria species, is maintained in a field collection of the Fruit Genebank at Dresden-Pillnitz. OBJECTIVE: A duplicate collection stored in liquid nitrogen would provide a higher level of security for these irreplaceable genetic resources. MATERIALS AND METHODS: Four distinct cryopreservation protocols were tested earlier and the best method, a PVS2 vitrification method with a 14-day alternating-temperature cold acclimation, was modified for further genotype screening. RESULTS: A comprehensive genotype spectrum was tested by screening 107 Fragaria ×ananassa cultivars and 20 Fragaria wild species (51 accessions). The average recovery for the cultivars using the optimized medium was 89.55 % and for the wild species 85.50 %. CONCLUSION: These results indicate that the method could be used to establish a backup collection in liquid nitrogen. Meristem cultures will be established and the collection will be cryopreserved using this vitrification technique to provide cost effective long-term storage.

Ontogenetic tissue modification in Malus fruit peduncles: the role of sclereids.

BACKGROUND AND AIMS: Apple (Malus) fruit peduncles are highly modified stems with limited secondary growth because fruit ripening lasts only one season. They must reliably connect rather heavy fruits to the branch and cope with increasing fruit weight, which induces dynamic stresses under oscillating wind loads. This study focuses on tissue modification of these small, exposed structures during fruit development. METHODS: A combination of microscopic, static and dynamic mechanical tests, as well as Raman spectroscopy, was used to study structure-function relationships in peduncles of one cultivar and 12 wild species, representatively chosen from all sections of the genus Malus. Tissue differentiation and ontogenetic changes in mechanical properties of Malus peduncles were observed throughout one growing season and after successive removal of tissues. KEY RESULTS: Unlike in regular stems, the vascular cambium produces mainly phloem during secondary growth. Hence, in addition to a reduced xylem, all species developed a centrally arranged sclerenchyma ring composed of fibres and brachysclereids. Based on differences in cell-wall thickness, and proportions and arrangement of sclereids, two types of peduncle construction could be distinguished. Fibres provide an increased maximum tensile strength and contribute most to the overall axial rigidity of the peduncles. Sclereids contribute insignificantly to peduncle strength; however, despite being shown to have a lower elastic modulus than fibres, they are the most effective tissue in stiffening peduncles against bending. CONCLUSIONS: The experimental data revealed that sclereids originating from cortical parenchyma act as 'accessory' cells to enhance proportions of sclerenchyma during secondary growth in peduncles. The mechanism can be interpreted as an adaptation to continuously increasing fruit loads. Under oscillating longitudinal stresses, sclereids may be regarded as regulating elements between maintenance of stiffness and viscous damping, the latter property being attributed to the cortical parenchyma.

Pomological and Molecular Characterization of Apple Cultivars in the German Fruit Genebank.

Traditional varieties are a valuable tool in modern apple breeding. However, the use of synonyms and missing source documentation hinder an effective identification and conservation of relevant cultivars. During several projects, the authenticity and diversity of the apple cultivar collection of the German Fruit Genebank (GFG) was evaluated extensively. The trueness-to-type of 7890 apple trees was assessed on a pomological and molecular level. Pomological evaluations were performed by at least two experienced experts to identify the original cultivar names. On the molecular level, a set of 17 SSR markers was used to determine a unique genetic profile for each apple cultivar. The pomological and molecular characterization was expressed in terms of a comprehensive trueness-to-type criterion and the results were previously published as a well-curated dataset. In this study, the published dataset was analyzed to evaluate the quality and diversity of the apple collection of the GFG and highlight new findings based on phylogenetic and parentage analysis. The dataset contains 1404 unique genetic profiles corresponding to unambiguous cultivar names. Of these 1404 cultivars, 74% were assessed as true-to-type. The collection of diploid apple cultivars showed a high degree of expected heterozygosity (Hexp = 0.84). Genetic diversity in terms of year and location of origin was investigated with a STRUCTURE analysis. It was hypothesized that genetic diversity might decline overtime due to restrictive breeding programs. The results showed a shift dynamic between older and newer cultivars in one specific cluster, but no significant decrease in genetic diversity was observed in this study. Lastly, a parentage analysis was performed to check parental relationships based on historical research. Out of 128 parent-child trios, 110 trios resulted in significant relationships and reconfirmed the information from the literature. In some cases, the information from the literature was disproven. This analysis also allowed for readjusting the trueness-to-type criteria for previously undetermined cultivars. Overall, the importance of authenticity evaluations for gene bank cultivars was highlighted. Furthermore, the direct use of the dataset was shown by relevant investigations on the genetic diversity and structure of the apple cultivar collections of the GFG.

Severe acute myositis and myocarditis on initiation of 6-weekly pembrolizumab post-COVID-19 mRNA vaccination.

We describe three cases of critical acute myositis with myocarditis occurring within 22 days of each other at a single institution, all within 1 month of receiving the initial cycle of the anti-PD-1 drug pembrolizumab. Analysis of T cell receptor repertoires from peripheral blood and tissues revealed a high degree of clonal expansion and public clones between cases, with several T cell clones expanded within the skeletal muscle putatively recognizing viral epitopes. All patients had recently received a COVID-19 mRNA booster vaccine prior to treatment and were positive for SARS-CoV2 Spike antibody. In conclusion, we report a series of unusually severe myositis and myocarditis following PD-1 blockade and the COVID-19 mRNA vaccination.