Imported Monkeypox from International Traveler, Maryland, USA, 2021.

A case of monkeypox was diagnosed in a returning traveler from Nigeria to Maryland, USA. Prompt infection control measures led to no secondary cases in 40 exposed healthcare workers. Given the global health implications, public health systems should be aware of effective strategies to mitigate the potential spread of monkeypox.

Domestically Acquired Seoul Virus Causing Hemophagocytic Lymphohistiocytosis-Washington, DC, 2018.

Seoul orthohantavirus (SEOV) infections, uncommonly reported in the United States, often result in mild illness. We report a case of hemophagocytic lymphohistiocytosis secondary to SEOV infection that was domestically acquired in Washington, DC.

Dalbavancin for the treatment of acute bacterial skin and skin structure infections.

INTRODUCTION: Acute bacterial skin and skin structure infections (ABSSSI) have increased in incidence and severity. The involvement of resistant organisms, particularly methicillin-resistant Staphylococcus aureus, presents additional challenges. The lipoglycopeptide dalbavancin has a prolonged half-life, high protein binding, and excellent tissue levels which led to its development as a once-weekly treatment for ABSSSI. In the pivotal DISCOVER 1 and DISCOVER 2 trials, dalbavancin proved non-inferior to vancomycin followed by linezolid when used sequentially for ABSSSI, forming the basis for its recent approval in the US and Europe for ABSSSI. AREAS COVERED: A literature search of published pharmacologic and clinical data was conducted to review the chemistry, pharmacodynamics, and pharmacokinetics of dalbavancin. We also discuss its development process, highlighting efficacy and safety data from pertinent clinical trials and the role it could play in the current clinical landscape. EXPERT OPINION: DISCOVER 1 and DISCOVER 2 demonstrated dalbavancin's non-inferiority to vancomycin followed by linezolid for ABSSSI and confirmed its safety and tolerability. They were among the first trials to use new, early primary efficacy endpoints, and dalbavancin was among the first agents designated a Qualified Infectious Disease Product for expedited review. Dalbavancin may prove to be a valuable option for ABSSSI patients in whom conventional therapy is limited.

APOE is a potential modifier gene in an autosomal dominant form of frontotemporal dementia (IBMPFD).

PURPOSE: Inclusion-body myopathy, Paget's disease of bone and frontotemporal dementia is an adult-onset autosomal dominant illness (IBMPFD) caused by mutations in the valosin-containing protein (VCP) on chromosome 9p21.1-p12. The penetrance of the gene is 82% for myopathy, 49% for Paget's disease, but may be as low as 30% for frontotemporal dementia. Modifier genes could account for decreased frontotemporal dementia penetrance. In this study apolipoprotein-E (APOE) was evaluated for this role in IBMPFD families based on its known modifier effect in Alzheimer's disease. METHODS: From a database of 231 members of 15 families, 174 had APOE genotype available for analysis. Logistic regressions on APOE genotype and frontotemporal dementia were performed, using appropriate covariates. RESULTS AND CONCLUSION: FTD was associated with APOE 4 genotype (P=0.0002), myopathy (P=0.0006), and age (P=0.01), but not microtubule associated protein tau (MAPT) H2 haplotype (P=0.5) or gender (0.09) after adjustment for membership in pedigrees with at least one APOE 4 genotype. These data suggest a potential link between APOE 4 genotype and the specific form of frontotemporal dementia found in IBMPFD. The molecular basis of this link bears further investigation. We did not observe an association of frontotemporal dementia and H2 MAPT haplotype.

Manifestations in a family with autosomal dominant bone fragility and limb-girdle myopathy.

We report on an unusual family with an autosomal dominant limb-girdle type of myopathy and bone fragility. This family was previously reported by Henry et al. [1958] as autosomal dominant progressive limb girdle "muscular dystrophy" with propensity to fractures and defective healing of long bones. Clinical, biochemical, and radiological aspects were evaluated in eight living relatives in this family (three males and five females) and in eight deceased individuals. The average age-of-onset of the limb-girdle myopathy was 31 years occurring in 87% of affected individuals. The average age of onset of fractures was 24 years occurring in 88% of affected individuals. Biochemical analysis showed a mean alkaline phosphatase (ALP) of 64 U/L (normal 30-120) and borderline high creatine kinase (CK) of 213 U/L (normal 4-220). Radiographs revealed coarse trabeculation, patchy sclerosis, cortical thickening, and narrowing of the medullary cavity with an appearance not considered typical of Paget disease of bone (PDB) or of fibrous dysplasia. Results of nerve conduction studies were normal, and electromyograms and muscle biopsies documented non-specific myopathic changes. There is premature graying with thin hair, thin skin, hernias and the affected individuals appear older than their chronological age, and three members had a clotting disorder. Linkage analysis for markers for the chromosome 9p22.3-q12 locus indicated that the disorder in this family does not segregate with markers in the critical region of limb-girdle/inclusion body myopathy, PDB, and frontotemporal dementia (FTD) [IBMPFD, OMIM #605382]. Sequencing of Valosin-containing protein (VCP), the gene associated with IBMPFD, did not identify mutations. We have excluded linkage to the known loci for limb-girdle type of myopathy and bone disease and excluded several candidate genes. Elucidation of the novel molecular basis of this disorder may provide valuable links between bone, collagen and muscle, and targeted therapeutic options.

Mapping autosomal dominant progressive limb-girdle myopathy with bone fragility to chromosome 9p21-p22: a novel locus for a musculoskeletal syndrome.

Progressive myopathy of a limb-girdle distribution and bone fragility is a rare autosomal dominant disorder of unknown etiology. Affected individuals, within this family, present with various combinations of progressive muscle weakness, easy fracturing, and poor healing of long bones. Additional features include premature graying with thin hair, thin skin, hernias, and clotting disorders. Electromyograms show myopathic changes and biopsies reveal non-specific myopathic changes. Skeletal radiographs demonstrate coarse trabeculation, patchy sclerosis, cortical thickening, and narrowing of medullary cavities. We report genetic mapping of this disorder to chromosome 9p21-p22 in a multigenerational family. A genome-wide scan for the disease locus obtained a maximal LOD score of 3.74 for marker GATA87E02 N (D9S1121). Haplotype analysis localized the disease gene within a 15 Mb interval flanked by markers AGAT142P and GATA5E06P. This region also localizes diaphyseal medullary stenosis with malignant fibrous histiocytoma (DMS-MFH). Identification of the disease gene will be necessary to understand the pathogenesis of this complex disorder.