Respiratory and sleep outcomes in children with SMA treated with nusinersen - real world experience.

It is unclear how improvements in peripheral motor function in children with spinal muscular atrophy (SMA), treated with nusinersen, translate into clinically significant respiratory/sleep outcomes. A retrospective chart review of SMA children at the Sydney Children's Hospital Network was undertaken looking at 2 years before and after receiving their first dose of nusinersen. Polysomnography (PSG), spirometry and clinical data were collected and analysed using paired and unpaired t-tests for PSG parameters and generalised estimating equations for longitudinal lung function data. Forty-eight children (10 Type 1, 23 Type 2, 15 Type 3) at mean age 6.98 yrs (SD 5.25) for nusinersen initiation were included. There was a statistically significant improvement in oxygen nadir during sleep in individuals post nusinersen (mean of 87.9% to 92.3% (95%CI 1.24 - 7.63, p = 0.01)). Based on clinical and PSG findings, 6/21 patients (5 Type 2, 1 Type 3) ceased nocturnal NIV post nusinersen. Non-significant improvements were demonstrated in mean slope for FVC% predicted, FVC Z-score and mean FVC% predicted. Within 2 years of commencing nusinersen, stabilisation of respiratory outcomes occurred. Whilst some of the SMA type 2/3 cohort ceased NIV, there were no statistically significant improvements lung function and most PSG parameters.

Perfil clínico e incidência de eventos cardiovasculares em 36 meses em pacientes com Minoca: registro de 126 pacientes em um hospital terciário de cardiologia / Clinical profile and incidence of cardiovascular events at 36 months in patients with Minoca: registry of 126 patients in a tertiary cardiology hospital

INTRODUÇÃO: Em 5% a 6% dos IAM não são observadas lesões obstrutivas maiores que 50%, sendo estes classificados como MINOCA (Infarto do Miocárdio com Artérias Coronárias não Obstrutivas). Estudos maiores de longo prazo demonstraram que o prognóstico desses pacientes não é benigno com risco aumentado de morte e novos eventos cardiovasculares. MÉTODOS: Nesta coorte de centro único, todos os pacientes que preencheram os critérios diagnósticos para MINOCA com (1) IAM (2) ausência de estenose coronária ≥ 50% na artéria relacionada ao infarto e (3) nenhuma outra causa específica clinicamente evidente entre março de 2000 e junho de 2022 foram incluídos com um acompanhamento médio de 30 (9,5-67,3) meses. As características da amostra foram descritas em frequências e valores medianos (p25%-p75%). A incidência de um novo evento cardiovascular (CV) em 36 meses após a MINOCA foi estimada pelo método de Kaplan-Meier e o teste de log-rank aplicado para comparar os grupos, acompanhado de intervalos de confiança de 95% e alfa de 5% (R 3,6,1 para MacOS). RESULTADOS: Dos 126 pacientes, 57,1% eram mulheres com cerca de 50 anos de idade (42,0-57,8). 20,6% tinham diabetes, 47,6% dislipidemia, 60,3% hipertensão e 20% IAM prévio. A apresentação clínica predominante foi IAMSSST (55,6%) e 7 pacientes tiveram um episódio de morte súbita abortada durante a internação. 38,1% dos pacientes não tiveram uma etiologia identificada. O mecanismo fisiopatológico mais prevalente foi ruptura da placa < 50% (16,7%), seguido de tromboembolismo (13,5%) e dissecção espontânea de coronária (13,5%). Apenas 3,2% realizaram tomografia de coerência óptica (OCT) ou ultrassom intravascular (IVUS). Nenhum teste provocativo foi realizado. 44,4% realizaram ressonância magnética cardíaca (RMC), com mediana de tempo para realização de 180,0 (60,0-707,5) dias após o evento. Em relação à medicação prescrita na alta hospitalar, 79,4% tiveram betabloqueador e IECA/BRA prescritos, 14,3% iniciaram anticoagulação e apenas 34,1% receberam dupla antiagregação plaquetária (DAP). A incidência do desfecho composto (morte CV, novo IAM, AVC e internação CV) em 36 meses foi de 15% (IC95% 8,9%-24,6%). A incidência de novo IAM foi de 6,3% (N=8), de AVC 2,4% (N=3), de hospitalização CV 17,5% (N=22) e apenas um óbito. CONCLUSÃO: Chama a atenção o risco do desfecho primário em 36 meses. Notavelmente, a maior parte da incidência foi atribuída à hospitalização CV. Um número importante de pacientes recebeu alta sem etiologia conhecida para sua apresentação clínica e, consequentemente, sem tratamento individualizado.

Treatment of a femoral septic nonunion in a dog with interlocking nail stabilization associated to corticospongious bone autograft and greater omentum flap: case report / Tratamento de não união séptica femoral em cão com estabilização com haste intramedular bloqueada associada a autoenxerto de osso corticoesponjoso e retalho do omento maior: relato de caso

Chronic septic bone nonunion requires a well-designed therapeutic planning, demanding a multimodal treatment to achieve bone consolidation and elimination of infection. A successful case of an association of the major omentum flap with surgical stabilization with an interlocking nail for treatment of a femoral septic nonunion in dog is reported. The patient had partial functional return of the limb 30 days after surgery, negative bacterial culture with radiographic signs of bone healing and total functional return of the limb at 90th days after the surgical procedure.(AU)

Não uniões ósseas associadas à osteomielite crônica necessitam de um planejamento terapêutico muito bem realizado, demandando tratamento multimodal para conseguir atingir a consolidação óssea e eliminar a infecção. Relatou-se um caso de sucesso do uso da associação de retalho do omento maior com estabilização cirúrgica com haste intramedular bloqueada para tratamento de uma não união séptica de fêmur em cão. O paciente apresentou retorno funcional parcial do membro com 30 dias após a cirurgia, cultura bacteriana estéril com sinais radiográficos de consolidação óssea e retorno funcional total do membro aos 90 dias de pós-operatório.(AU)

Genetic diversity and patterns of population structure in Creole goats from the Americas.

Biodiversity studies are more efficient when large numbers of breeds belonging to several countries are involved, as they allow for an in-depth analysis of the within- and between-breed components of genetic diversity. A set of 21 microsatellites was used to investigate the genetic composition of 24 Creole goat breeds (910 animals) from 10 countries to estimate levels of genetic variability, infer population structure and understand genetic relationships among populations across the American continent. Three commercial transboundary breeds were included in the analyses to investigate admixture with Creole goats. Overall, the genetic diversity of Creole populations (mean number of alleles = 5.82 ± 1.14, observed heterozygosity = 0.585 ± 0.074) was moderate and slightly lower than what was detected in other studies with breeds from other regions. The Bayesian clustering analysis without prior information on source populations identified 22 breed clusters. Three groups comprised more than one population, namely from Brazil (Azul and Graúna; Moxotó and Repartida) and Argentina (Long and shorthair Chilluda, Pampeana Colorada and Angora-type goat). Substructure was found in Criolla Paraguaya. When prior information on sample origin was considered, 92% of the individuals were assigned to the source population (threshold q ≥ 0.700). Creole breeds are well-differentiated entities (mean coefficient of genetic differentiation = 0.111 ± 0.048, with the exception of isolated island populations). Dilution from admixture with commercial transboundary breeds appears to be negligible. Significant levels of inbreeding were detected (inbreeding coefficient > 0 in most Creole goat populations, P < 0.05). Our results provide a broad perspective on the extant genetic diversity of Creole goats, however further studies are needed to understand whether the observed geographical patterns of population structure may reflect the mode of goat colonization in the Americas.

Successful use of autogenous bone graft for the treatment of a radius-ulna nonunion in an amputee dog / Uso de enxerto ósseo autógeno no tratamento de uma não união óssea em um radioulna de um canino amputado

Fracture nonunions represent important complications in orthopedic surgeries. Nonunion repairs or bone defects are surgically challenging. Our aim was to describe a nonunion case, which was repaired with rapid bone recovery. An 8-month-old male mixed breed dog that has been previously operated was presented to the Veterinary Medical Teaching Hospital of São Paulo State University, with a right radius-ulna nonunion and an amputated contralateral forelimb. A cancellous bone graft was collected from a partially amputated limb, in order to correct the nonunion, and used in association with a locking plate. After four weeks, the bone graft had been incorporated into the original bone. Clinical union with good weight bearing was achieved after eight weeks.

As não uniões ósseas representam uma importante complicação nas cirurgias ortopédicas. Não uniões ósseas ou defeitos ósseos são um desafio na cirurgia. O objetivo do presente trabalho foi descrever um caso de não união óssea, que foi reparada de forma rápida. Um cão SRD de oito meses, macho, que havia sido operado previamente, deu entrada no Hospital Veterinário da Unesp - Jaboticabal com uma não união óssea em radioulna e o membro contralateral amputado. Um enxerto ósseo autógeno foi coletado do coto do membro contralateral amputado e utilizado junto a uma placa óssea bloqueada para o tratamento. Após quatro semanas, o enxerto ósseo estava incorporado ao osso original. A união clínica e o retorno normal à função foram alcançados após oito semanas.

Importance and challenge of making an early diagnosis in LMNA-related muscular dystrophy.

OBJECTIVE: To identify the most useful clinical and histologic markers that facilitate early diagnosis in LMNA-related muscular dystrophy and to assess the usefulness of Western blotting (WB) for lamin A/C. METHODS: We analyzed the clinical and histologic features and WB results of all patients with laminopathies diagnosed in a research-based diagnostic service over 8 years. RESULTS: Although patients with congenital muscular dystrophy (MDCL) (n = 5) and Emery-Dreifuss muscular dystrophy (EDMD) (n = 5) had distinctive early clinical features, the lack of a suggestive clinical phenotype significantly delayed diagnosis in 2 of 3 patients with limb-girdle muscular dystrophy (LGMD) (n = 3). In addition, 6 of 20 muscle biopsy samples were considered nondystrophic, which contributed to delays in diagnosis in some patients. Neck extensor involvement (weakness or contractures) was the most consistent clinical sign, present in all patients. Reduced lamin A/C levels on WB were seen in 5 of 9 patients with laminopathies. CONCLUSION: Clinical features provide the best clues for diagnosing MDCL and EDMD early in the disease, and we urge clinicians to become familiar with those phenotypes. WB for lamin A/C may contribute to diagnosis but requires technical expertise, and results are normal in many individuals with LMNA mutations. Because of the survival benefit of early diagnosis and treatment, we recommend that LMNA gene sequencing be performed in all patients with undiagnosed congenital muscular dystrophy and neck extensor weakness, all patients with genetically undiagnosed LGMD, and those with suggestive clinical signs and nonspecific histologic abnormalities.

Drift across the Atlantic: genetic differentiation and population structure in Brazilian and Portuguese native goat breeds.

Brazilian goat breeds are believed to derive mainly from animals brought by Portuguese settlers since the 16th century. We used microsatellite markers in a sample of 436 animals to study genetic variability and differentiation of the six Portuguese (PT) and six Brazilian (BR) goat breeds currently recognized in the two countries. These breeds were also compared with an outgroup represented by a sample of Alpine (ALP) goats. The effective number of alleles and allelic richness were slightly higher in PT than in BR breeds. The global F(ST) was nearly 0.11 when PT and BR breeds were considered, with a mean pairwise F(ST) of about 0.03 among PT breeds, 0.07 among BR breeds and 0.15 between PT and BR breeds. The dendrogram illustrating relationships between populations and the correspondence analysis indicate the existence of two very distinct clusters, corresponding to the countries of origin of the breeds studied, which are nearly equidistant from the Alpine outgroup. The analysis with structure confirmed the separation between PT and BR breeds but suggests that some BR breeds, especially Graúna and Canindé, may share a common ancestry with PT breeds. The divergence observed between PT and BR breeds may result from founder effects and genetic drift but could also reflect the introduction in Brazil of goats originating from other regions, e.g., West Africa.