Frailty and cardiac surgery: to operate or not?

PURPOSE OF REVIEW: With an aging cardiac surgery population, prefrail and frail patients are becoming more common. Anesthesiologists will be faced with the decision of how best to provide care to frail patients. Identification, management, and outcomes in frail patients will be discussed in this review. RECENT FINDINGS: Frailty is associated with a variety of poor outcomes, such as increased hospital length of stay, medical resource utilization, readmission rates, and mortality. Prehabilitation may play a greater role in the management of frail cardiac surgery patients. SUMMARY: As frailty will likely only increase amongst cardiac surgery patients, it is important to develop multicenter trials to study management and treatment options. Until those studies are performed, the care of frail cardiac surgery patients may be best provided by high-volume surgical centers with expertise in the management of frail patients.

Genetic analysis of 10 pedigrees with inherited retinal degeneration by exome sequencing and phenotype-genotype association.

Our purpose was to identify causative mutations and characterize the phenotype associated with the genotype in 10 unrelated families with autosomal recessive retinal degeneration. Ophthalmic evaluation and DNA isolation were carried out in 10 pedigrees with inherited retinal degenerations (IRD). Exomes of probands from eight pedigrees were captured using Nimblegen V2/V3 or Agilent V5+UTR kits, and sequencing was performed on Illumina HiSeq. The DHDDS gene was screened for mutations in the remaining two pedigrees with Ashkenazi Jewish ancestry. Exome variants were filtered to detect candidate causal variants using exomeSuite software. Segregation and ethnicity-matched control sample analysis were performed by dideoxy sequencing. Retinal histology of a patient with DHDDS mutation was studied by microscopy. Genetic analysis identified six known mutations in ABCA4 (p.Gly1961Glu, p.Ala1773Val, c.5461-10T>C), RPE65 (p.Tyr249Cys, p.Gly484Asp), PDE6B (p.Lys706Ter) and DHDDS (p.Lys42Glu) and ten novel potentially pathogenic variants in CERKL (p.Met323Val fsX20), RPE65 (p.Phe252Ser, Thr454Leu fsX31), ARL6 (p.Arg121His), USH2A (p.Gly3142Ter, p.Cys3294Trp), PDE6B (p.Gln652Ter), and DHDDS (p.Thr206Ala) genes. Among these, variants/mutations in two separate genes were observed to segregate with IRD in two pedigrees. Retinal histopathology of a patient with a DHDDS mutation showed severe degeneration of retinal layers with relative preservation of the retinal pigment epithelium. Analysis of exome variants in ten pedigrees revealed nine novel potential disease-causing variants and nine previously reported homozygous or compound heterozygous mutations in the CERKL, ABCA4, RPE65, ARL6, USH2A, PDE6B, and DHDDS genes. Mutations that could be sufficient to cause pathology were observed in more than one gene in one pedigree.

Protection levels of N95-level respirator substitutes proposed during the COVID-19 pandemic: safety concerns and quantitative evaluation procedures.

OBJECTIVE: The COVID-19 pandemic has precipitated widespread shortages of filtering facepiece respirators (FFRs) and the creation and sharing of proposed substitutes (novel designs, repurposed materials) with limited testing against regulatory standards. We aimed to categorically test the efficacy and fit of potential N95 respirator substitutes using protocols that can be replicated in university laboratories. SETTING: Academic medical centre with occupational health-supervised fit testing along with laboratory studies. PARTICIPANTS: Seven adult volunteers who passed quantitative fit testing for small-sized (n=2) and regular-sized (n=5) commercial N95 respirators. METHODS: Five open-source potential N95 respirator substitutes were evaluated and compared with commercial National Institute for Occupational Safety and Health (NIOSH)-approved N95 respirators as controls. Fit testing using the 7-minute standardised Occupational Safety and Health Administration fit test was performed. In addition, protocols that can be performed in university laboratories for materials testing (filtration efficiency, air resistance and fluid resistance) were developed to evaluate alternate filtration materials. RESULTS: Among five open-source, improvised substitutes evaluated in this study, only one (which included a commercial elastomeric mask and commercial HEPA filter) passed a standard quantitative fit test. The four alternative materials evaluated for filtration efficiency (67%-89%) failed to meet the 95% threshold at a face velocity (7.6 cm/s) equivalent to that of a NIOSH particle filtration test for the control N95 FFR. In addition, for all but one material, the small surface area of two 3D-printed substitutes resulted in air resistance that was above the maximum in the NIOSH standard. CONCLUSIONS: Testing protocols such as those described here are essential to evaluate proposed improvised respiratory protection substitutes, and our testing platform could be replicated by teams with similar cross-disciplinary research capacity. Healthcare professionals should be cautious of claims associated with improvised respirators when suggested as FFR substitutes.

Investigating the Molecular Basis of Retinal Degeneration in a Familial Cohort of Pakistani Decent by Exome Sequencing.

PURPOSE: To define the molecular basis of retinal degeneration in consanguineous Pakistani pedigrees with early onset retinal degeneration. METHODS: A cohort of 277 individuals representing 26 pedigrees from the Punjab province of Pakistan was analyzed. Exomes were captured with commercial kits and sequenced on an Illumina HiSeq 2500. Candidate variants were identified using standard tools and analyzed using exomeSuite to detect all potentially pathogenic changes in genes implicated in retinal degeneration. Segregation analysis was performed by dideoxy sequencing and novel variants were additionally investigated for their presence in ethnicity-matched controls. RESULTS: We identified a total of nine causal mutations, including six novel variants in RPE65, LCA5, USH2A, CNGB1, FAM161A, CERKL and GUCY2D as the underlying cause of inherited retinal degenerations in 13 of 26 pedigrees. In addition to the causal variants, a total of 200 variants each observed in five or more unrelated pedigrees investigated in this study that were absent from the dbSNP, HapMap, 1000 Genomes, NHLBI ESP6500, and ExAC databases were identified, suggesting that they are common in, and unique to the Pakistani population. CONCLUSIONS: We identified causal mutations associated with retinal degeneration in nearly half of the pedigrees investigated in this study through next generation whole exome sequencing. All novel variants detected in this study through exome sequencing have been cataloged providing a reference database of variants common in, and unique to the Pakistani population.

Evaluation of serum levels of interleukin-6 and interleukin-10 in patients undergoing laparoscopic versus conventional cholecystectomy.

OBJECTIVE: To correlate serum preoperative and postoperative interleukin-6 and interleukin-10 levels in patients undergoing laparotomy versus laparoscopic cholecystectomy. METHODS: From a total of 20 patients, 18 were included in the study, nine underwent cholecystectomy by laparoscopy and the other nine by laparotomy. Serum concentrations of IL-6 and IL-10 were measured in both groups. Blood samples were obtained in the times of 24 hours preoperatively and four, 12 and 24 hours after the procedure. The groups were compared regarding age, gender, body mass index (BMI), duration of anesthesia and operation. RESULTS: There was no significant statistical differences between groups related to age, gender, BMI, duration of anesthesia and operation. The comparison between the two procedurs demonstrated statistical differences for IL-6 in time 12 hours after operation (218.64 pg/ml laparotomic versus 67.71 pg/ml laparoscopic, p = 0.0003) and for IL-10 in time 24 hours after the procedure (24.46 pg/ml open versus 10.17 pg/qml laparoscopic, p <0.001). CONCLUSION: There was an Increase in plasma levels of interleukin-6 and 10 after surgical trauma with a significant increase in levels of interleukins in the laparotomic group in comparison with the laparoscopic group.

Exome analysis identified a novel mutation in the RBP4 gene in a consanguineous pedigree with retinal dystrophy and developmental abnormalities.

Retinitis Pigmentosa (RP) is a common form of retinal degeneration characterized by photoreceptor degeneration and retinal pigment epithelium (RPE) atrophy causing loss of visual field and acuities. Exome sequencing identified a novel homozygous splice site variant (c.111+1G>A) in the gene encoding retinol binding protein 4 (RBP4). This change segregated with early onset, progressive, and severe autosomal recessive retinitis pigmentosa (arRP) in an eight member consanguineous pedigree of European ancestry. Additionally, one patient exhibited developmental abnormalities including patent ductus arteriosus and chorioretinal and iris colobomas. The second patient developed acne from young age and extending into the 5(th) decade. Both patients had undetectable levels of RBP4 in the serum suggesting that this mutation led to either mRNA or protein instability resulting in a null phenotype. In addition, the patients exhibited severe vitamin A deficiency, and diminished serum retinol levels. Circulating transthyretin levels were normal. This study identifies the RBP4 splice site change as the cause of RP in this pedigree. The presence of developmental abnormalities and severe acne in patients with retinal degeneration may indicate the involvement of genes that regulate vitamin A absorption, transport and metabolism.

Ipsilateral eye cortical maps are uniquely sensitive to binocular plasticity.

In the cerebral cortex, neuronal circuits are first laid down by intrinsic mechanisms and then refined by experience. In the canonical model, this refinement is driven by activity-dependent competition between inputs for some limited cortical resource. Here we examine this idea in the mouse visual cortex at the peak of the critical period for experience-dependent plasticity. By imaging intrinsic optical responses, we mapped the strength and size of each eye's cortical representation in normal mice, mice that had been deprived of patterned vision uni- or bilaterally, and in mice in which the contralateral eye had been removed. We find that for both eyes, a period of visual deprivation results in a loss of cortical responsiveness to stimulation through the deprived eye. In addition, the ipsilateral eye pathway is affected by the quality of vision through the opposite eye. Our findings indicate that although both contra- and ipsilateral eye pathways require visual experience for their maintenance, ipsilateral eye projections bear an additional, unique sensitivity to binocular interactions.

Avaliação dos níveis séricos de interleucina-6 e interleucina-10 nos pacientes submetidos à colecistectomia laparoscópica versus convencional / Evaluation of serum levels of interleukin-6 and interleukin-10 in patients undergoing laparoscopic versus conventional cholecystectomy

OBJETIVO: Correlacionar a dosagem sérica pré-operatória e pós-operatória de interleucina-6 (IL-6) e interleucina-10 (IL-10) entre pacientes submetidos à colecistectomia laparotômica versus videolaparoscópica. MÉTODOS: De um total de 20 pacientes, 18 foram incluídos no estudo, sendo nove submetidos à colecistectomia laparoscópica e os outros nove utilizando a técnica laparotômica. As concentrações séricas de IL-6 e IL-10 foram dosadas em ambos os grupos. As amostras de sangue foram obtidas nos tempos de 24 horas no pré-operatório, quatro, 12 e 24 horas após o procedimento. Os grupos foram comparados em relação à idade, sexo, índice de massa corpórea (IMC), tempo de anestesia e de operação. RESULTADOS: Não houve diferenças significativamente estatísticas entre os grupos relacionadas à idade, sexo, IMC, tempo de anestesia e de operação. A comparação entre a colecistectomia laparotômica e laparoscópica demonstrou diferenças estatísticas nos níveis de IL-6 no tempo 12 horas após operação (218,64pg/ml laparotômica versus 67,71pg/ml laparoscópica, p=0,0003) e IL-10 no tempo de 24 horas após o procedimento (24,46pg/ml aberta versus 10,17pg/ml laparoscópica, p <0,001). CONCLUSÃO: Houve aumento das dosagens de interleucinas-6 e 10 após o trauma cirúrgico. Ocorreu aumento significativo dos níveis das interleucinas analisadas no grupo laparotômico em comparação com o grupo laparoscópico.

OBJECTIVE: To correlate serum preoperative and postoperative interleukin-6 and interleukin-10 levels in patients undergoing laparotomy versus laparoscopic cholecystectomy. METHODS: From a total of 20 patients, 18 were included in the study, nine underwent cholecystectomy by laparoscopy and the other nine by laparotomy. Serum concentrations of IL-6 and IL-10 were measured in both groups. Blood samples were obtained in the times of 24 hours preoperatively and four, 12 and 24 hours after the procedure. The groups were compared regarding age, gender, body mass index (BMI), duration of anesthesia and operation. RESULTS: There was no significant statistical differences between groups related to age, gender, BMI, duration of anesthesia and operation. The comparison between the two procedurs demonstrated statistical differences for IL-6 in time 12 hours after operation (218.64 pg/ml laparotomic versus 67.71 pg/ml laparoscopic, p = 0.0003) and for IL-10 in time 24 hours after the procedure (24.46 pg/ml open versus 10.17 pg/qml laparoscopic, p <0.001). CONCLUSION: There was an Increase in plasma levels of interleukin-6 and 10 after surgical trauma with a significant increase in levels of interleukins in the laparotomic group in comparison with the laparoscopic group.

Revisões femorais de artroplastias totais do quadril com afrouxamentos assépticos e fraturas periprotéticas: análise de 49 casos tratados com haste de Wagner / Femoral revision total hip arthroplasties with aseptic loosening and periprosthetic fractures. Analysis of 49 cases treated with Wagner stem

Objetivo: Avaliar 49 quadris em 48 pacientes submetidos a revisão de artroplastia total do quadril usando a haste de Wagner. Métodos: De abril de 1999 a janeiro de 2005, foram tratados 49 quadris em pacientes portadores de afrouxamento femoral (39 quadris) ou fratura periprotética do fêmur (10 quadris) com revisão da artroplastia com a prótese de Wagner. O seguimento médio foi de 35 meses e a média de idade, de 63,4 anos. As revisões do componente femoral foram realizadas em 49 quadris e, simultaneamente, no componente acetabular em 36 quadris. Resultados: A avaliação dos resultados pelo índice de D’Aubignè-Postel-Charnley apresentou melhora estatisticamente significante no pós-operatório em relação ao préoperatório (p < 0,001). Os problemas mais importantes foram o alto índice de luxações (três quadris) e de luxações associadas a afundamento da haste (dois quadris). Os quatro resultados insatisfatórios deveram-se a afrouxamento (dois quadris), infecção (um quadril) e afrouxamento acetabular (um quadril). Todos os resultados insatisfatórios ocorreram no grupo de afrouxamento asséptico, mas esse achado não foi estatisticamente significante (p = 0,569). A restauração do estoque ósseo (avaliação radiográfica) foi encontrada de modo consistente na maioria dos casos, sem correlação com a idade dos pacientes (p = 0,852). Os resultados clínicos não tiveram também relação com a idade dos pacientes (p = 0,636). Conclusão: O procedimento da revisão femoral com a prótese de Wagner produz resultados clínicos e radiográficos satisfatórios e, de modo consistente, restaura o estoque ósseo do fêmur.

Hérnia vesical inguinoescrotal gigante / Giant inguino-scrotal vesical hernia

A presença da bexiga urinária fazendo parte do conteúdo de uma hérnia inguinal é achado incomum, sendo encontrada em 0,4 a 3 por cento de todas as hérnias inguinais, e alcançando incidência de 10 por cento nos pacientes maiores de 50 anos. Objetivo - descrever um caso de hérnia inguinoescrotal em cujo conteúdo apresentava-se com queixa de aumento de volume em região inguinoescrotal à direita, com dor local aos esforços e associado com nictúria e micção em dois tempos / The presence of the urinary bladder as part of the contents of and inguinal hernia is not common; it is found in 0,4 to 3 per cent of inguinal hernias and reaches the incidence of 10 per cent in patients over age 50. Objective - the description of a case of inguinoscrotal hernia in a 52 years old, patient, in the contents of wich the urinary bladder was also found...