Comparison of the endotracheal cuff inflation techniques and its postoperative laryngotracheal morbidity: an observational study

Background: Endotracheal tubes cuffs are used to prevent gas leak and also pulmonary aspiration in mechanically ventilated patients. The commonly employed intubation techniques are the use of inflation to a constant pressure (25 cm H2O), sealing pressure and estimation of the cuff pressure by finger palpation. However, the use of the cuff inflation volumes may cause tracheal morbidity. The aim of the present study was to compare the effective tracheal seal and the incidence of post-intubation airway complications between the three techniques.Methods: 90 patients under N2O free general endotracheal anaesthesia were included in the study. They were randomly allotted into three groups consisting of 30 in each. After induction of anesthesia, endotracheal tubes size 7.0 mm for female and 8.5 mm for male were used. Constant pressure group (n=30), the cuff was inflated to a pressure of 25 cm H2O; sealing group (n=30), the cuff was inflated to prevent air leaks at airway pressure of 20 cm H2O and finger group (n=30), the cuff was inflated using finger estimation. Manometric cuff pressure and volume of air required to inflate the cuff, incidence of sore throat, hoarseness and dysphagia were tested.Results: Significant differences was not observed between the three groups in case of demographic data, ASA grading, endotracheal tube size used, number of attempts to place the endotracheal tubes, duration of intubation between the three groups. On the other hand, the cuff pressure, volume of air to fill the cuff and the incidence of sore throat was significantly higher in the finger group compared to other two groups (p ≤0.05). The incidence of dysphagia and hoarseness was also higher in finger palpitation group but the difference is insignificant.Conclusions: In cases of N2O free anesthesia, sealing cuff pressure is an easy and safe alternative technique compared to other two techniques, regarding effectiveness and low incidence of tracheal morbidities

A Rare Presentation of Controlled Chaos: Spontaneous Pneumothorax Under General Anaesthesia

Perioperative pneumothorax is a potentially dangerous and rare complication during general anaesthesia. Hereby the authors report a case of 25-year-old female, who was posted for a dental procedure, and developed spontaneous pneumothorax under general anaesthesia. The patient had no co-morbidities or risk factors during the perioperative period and classified as American Society of Anaesthesiologist’s (ASA) class I. She was planned under general anaesthesia with an orotracheal intubation with controlled positive pressure ventilation. At the end of the surgery, she developed significant respiratory changes which rose the suspicion of pneumothorax and later, it was confirmed radiologically. This early suspicion and early intervention by tube thoracostomy in Postanaesthesia Care Unit (PACU) stabilised the patient and resolved eventually. Early recognition and appropriate intervention can mitigate the perioperative outcome and reduce morbidity. Positive pressure ventilation, Positive End Expiratory Pressure (PEEP) and airway handling being the major predisposing factors for the development of pneumothorax. This further reiterates the need for keen perioperative vigilance for early recognition and appropriate management. Although rare, pneumothorax should be considered as differential diagnosis in crisis scenarios like tight bag

Use of whole genome sequencing to determine genetic basis of suspected mitochondrial disorders: cohort study.

OBJECTIVE: To determine whether whole genome sequencing can be used to define the molecular basis of suspected mitochondrial disease. DESIGN: Cohort study. SETTING: National Health Service, England, including secondary and tertiary care. PARTICIPANTS: 345 patients with suspected mitochondrial disorders recruited to the 100 000 Genomes Project in England between 2015 and 2018. INTERVENTION: Short read whole genome sequencing was performed. Nuclear variants were prioritised on the basis of gene panels chosen according to phenotypes, ClinVar pathogenic/likely pathogenic variants, and the top 10 prioritised variants from Exomiser. Mitochondrial DNA variants were called using an in-house pipeline and compared with a list of pathogenic variants. Copy number variants and short tandem repeats for 13 neurological disorders were also analysed. American College of Medical Genetics guidelines were followed for classification of variants. MAIN OUTCOME MEASURE: Definite or probable genetic diagnosis. RESULTS: A definite or probable genetic diagnosis was identified in 98/319 (31%) families, with an additional 6 (2%) possible diagnoses. Fourteen of the diagnoses (4% of the 319 families) explained only part of the clinical features. A total of 95 different genes were implicated. Of 104 families given a diagnosis, 39 (38%) had a mitochondrial diagnosis and 65 (63%) had a non-mitochondrial diagnosis. CONCLUSION: Whole genome sequencing is a useful diagnostic test in patients with suspected mitochondrial disorders, yielding a diagnosis in a further 31% after exclusion of common causes. Most diagnoses were non-mitochondrial disorders and included developmental disorders with intellectual disability, epileptic encephalopathies, other metabolic disorders, cardiomyopathies, and leukodystrophies. These would have been missed if a targeted approach was taken, and some have specific treatments

Use of whole genome sequencing to determine genetic basis of suspected mitochondrial disorders: cohort study

Funder: University of Cambridge; FundRef: http://dx.doi.org/10.13039/501100000735Funder: Alzheimer's Society; FundRef: http://dx.doi.org/10.13039/501100000320Funder: Leverhulme Trust; FundRef: http://dx.doi.org/10.13039/501100000275Funder: National Institute for Health Research; FundRef: http://dx.doi.org/10.13039/501100000272Funder: Department of Health; FundRef: http://dx.doi.org/10.13039/501100000276Funder: Evelyn Trust; FundRef: http://dx.doi.org/10.13039/501100004282Funder: Wellcome Trust; FundRef: http://dx.doi.org/10.13039/100004440Funder: Medical Research Council; FundRef: http://dx.doi.org/10.13039/501100000265Abstract: Objective: To determine whether whole genome sequencing can be used to define the molecular basis of suspected mitochondrial disease. Design: Cohort study. Setting: National Health Service, England, including secondary and tertiary care. Participants: 345 patients with suspected mitochondrial disorders recruited to the 100 000 Genomes Project in England between 2015 and 2018. Intervention: Short read whole genome sequencing was performed. Nuclear variants were prioritised on the basis of gene panels chosen according to phenotypes, ClinVar pathogenic/likely pathogenic variants, and the top 10 prioritised variants from Exomiser. Mitochondrial DNA variants were called using an in-house pipeline and compared with a list of pathogenic variants. Copy number variants and short tandem repeats for 13 neurological disorders were also analysed. American College of Medical Genetics guidelines were followed for classification of variants. Main outcome measure: Definite or probable genetic diagnosis. Results: A definite or probable genetic diagnosis was identified in 98/319 (31%) families, with an additional 6 (2%) possible diagnoses. Fourteen of the diagnoses (4% of the 319 families) explained only part of the clinical features. A total of 95 different genes were implicated. Of 104 families given a diagnosis, 39 (38%) had a mitochondrial diagnosis and 65 (63%) had a non-mitochondrial diagnosis. Conclusion: Whole genome sequencing is a useful diagnostic test in patients with suspected mitochondrial disorders, yielding a diagnosis in a further 31% after exclusion of common causes. Most diagnoses were non-mitochondrial disorders and included developmental disorders with intellectual disability, epileptic encephalopathies, other metabolic disorders, cardiomyopathies, and leukodystrophies. These would have been missed if a targeted approach was taken, and some have specific treatments

Primary renal echinococcosis

Echinococcosis is a parasitic infection caused by the larval stage of a cestode Echinococcus granulosus and is endemic in sheep farming regions of developing countries. It manifests as hydatid cyst and most commonly is found in liver followed by lungs. Renal hydatid cyst is rare and amounts for 2% of all cases. There are no specific clinical manifestations, and hence diagnosis of renal hydatid disease is missed out easily without imaging. We report a case of 50-year-old female who had 6 months history of lower abdominal pain with hematuria, found to have right renal hydatid cyst on imaging which was treated with right nephrectomy with pre- and post-operative albendazole treatment

Deep intronic variant causes aberrant splicing of ATP7A in a family with a variable occipital horn syndrome phenotype

Genetic variants in ATP7A are associated with a spectrum of X-linked disorders. In descending order of severity, these are Menkes disease, occipital horn syndrome, and X-linked distal spinal muscular atrophy. After 30 years of diagnostic investigation, we identified a deep intronic ATP7A variant in four males from a family affected to variable degrees by a predominantly skeletal phenotype, featuring bowing of long bones, elbow joints with restricted mobility which dislocate frequently, coarse curly hair, chronic diarrhoea, and motor coordination difficulties. Analysis of whole genome sequencing data from the Genomics England 100,000 Genomes Project following clinical re-evaluation identified a deep intronic ATP7A variant, which was predicted by SpliceAI to have a modest splicing effect. Using a mini-gene splicing assay, we determined that the intronic variant results in aberrant splicing. Sanger sequencing of patient cDNA revealed ATP7A transcripts with exon 5 skipping, or inclusion of a novel intron 4 pseudoexon. In both instances, frameshift leading to premature termination are predicted. Quantification of ATP7A mRNA transcripts using a qPCR assay indicated that the majority of transcripts (86.1 %) have non-canonical splicing, with 68.0 % featuring exon 5 skipping, and 18.1 % featuring the novel pseudoexon. We suggest that the variability of the phenotypes within the affected males results from the stochastic effects of splicing. This deep intronic variant, resulting in aberrant ATP7A splicing, expands the understanding of intronic variation on the ATP7A-related disease spectrum.</p

Newer Volatile Anesthetic Agents in Cardiac Anesthesia: Review of Literature

Myocardial protection with volatile anesthetic agents have been suggested by multiple studies. These studies, however, are scattered and are often limited to a particular aspect of cardiac anesthesia. Older inhalational agents like halothane is known to cause significant hepatic damage in patients undergoing long duration surgeries while isoflurane is known to have marked vasodilating properties that also affects the coronary arteries leading to coronary “steal” phenomenon. Additionally, newer agents, like sevoflurane and desflurane, have shown more prominent cardioprotective effects than older agents. We searched ScholarOne, Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library. The medical subject headings (MeSH) terms “anaesthesia, inhalational,” “anaesthesia, intravenous, or TIVA,” and “Cardiac anaesthesia or Cardiac Surgery” were used. Additional studies were identified by review of the reference sections of all eligible studies. The aim of this review article is to bring together the evidences with newer inhalational agents and provide a holistic view of their benefits and shortcomings in cardiac anesthesia

Biallelic variants in CENPF causing a phenotype distinct from Strømme syndrome

Biallelic loss-of-function (LoF) variants in CENPF gene are responsible for Strømme syndrome, a condition presenting with intestinal atresia, anterior ocular chamber anomalies, and microcephaly. Through an international collaboration, four individuals (three males and one female) carrying CENPF biallelic variants, including two missense variants in homozygous state and four LoF variants, were identified by exome sequencing. All individuals had variable degree of developmental delay/intellectual disability and microcephaly (ranging from -2.9 SDS to -5.6 SDS) and a recognizable pattern of dysmorphic facial features including inverted-V shaped interrupted eyebrows, epicanthal fold, depressed nasal bridge, and pointed chin. Although one of the cases had duodenal atresia, all four individuals did not have the combination of internal organ malformations of Strømme syndrome (intestinal atresia and anterior eye segment abnormalities). Immunofluorescence analysis on skin fibroblasts on one of the four cases with the antibody for ARL13B that decorates primary cilia revealed shorter primary cilia that are consistent with a ciliary defect. This case-series of individuals with biallelic CENPF variants suggests the spectrum of clinical manifestations of the disorder that may be related to CENPF variants is broad and can include phenotypes lacking the cardinal features of Strømme syndrome

Recurrent de novo missense variants across multiple histone H4 genes underlie a neurodevelopmental syndrome

Chromatin is essentially an array of nucleosomes, each of which consists of the DNA double-stranded fiber wrapped around a histone octamer. This organization supports cellular processes such as DNA replication, DNA transcription, and DNA repair in all eukaryotes. Human histone H4 is encoded by fourteen canonical histone H4 genes, all differing at the nucleotide level but encoding an invariant protein. Here, we present a cohort of 29 subjects with de novo missense variants in six H4 genes (H4C3, H4C4, H4C5, H4C6, H4C9, and H4C11) identified by whole-exome sequencing and matchmaking. All individuals present with neurodevelopmental features of intellectual disability and motor and/or gross developmental delay, while non-neurological features are more variable. Ten amino acids are affected, six recurrently, and are all located within the H4 core or C-terminal tail. These variants cluster to specific regions of the core H4 globular domain, where protein-protein interactions occur with either other histone subunits or histone chaperones. Functional consequences of the identified variants were evaluated in zebrafish embryos, which displayed abnormal general development, defective head organs, and reduced body axis length, providing compelling evidence for the causality of the reported disorder(s). While multiple developmental syndromes have been linked to chromatin-associated factors, missense-bearing histone variants (e.g., H3 oncohistones) are only recently emerging as a major cause of pathogenicity. Our findings establish a broader involvement of H4 variants in developmental syndromes