Improvement of visual acuity based on optical coherence tomography patterns following intravitreal bevacizumab treatment in patients with diabetic macular edema

<b>AIM:</b>To report the visual outcome based on various patterns of optical coherence tomography (OCT) morphology in diabetic macular edema (DME), following treatment with anti-VEGF intravitreal bevacizumab (IVB) injection.<b>METHODS:</b>Sixty-seven consecutive subjects with centre involving DME underwent intravitreal injection of Bevacizumab (1.25 mg/0.05 mL) in this retrospective, comparative, non randomized study. The DME was classified into one of four categories:focal, diffuse, focal cystoid and neurosensory detachment based on OCT. Best corrected visual acuity (BCVA), macular appearance, and OCT findings were used to decide whether the subject should have a repeat injection of intravitreal bevacizumab. Outcome measures were a change in mean BCVA (Snellen converted to logMAR) and central macular thickness (CMT) in each group during the six month follow-up period.<b>RESULTS:</b>The mean BCVA improved to logMAR 0.23 at final follow-up from a baseline of 0.32 logMAR (<i>P=</i>0.040) in the focal group, logMAR 0.80 at final follow-up from a baseline of 0.82 logMAR (<i>P=</i>0.838) in the diffuse group, worsened to logMAR 0.53 at final follow-up from a baseline of 0.43 logMAR (<i>P=</i>0.276) in the focal cystoid group, and improved to logMAR 0.79 at final follow-up from a baseline of 0.93 logMAR (<i>P=</i>0.490) in the neurosensory detachment group. The mean CMT before treatment were 298.8±25.03 μm in the focal group, 310.8±40.6 μm in the diffuse group, 397.15±31.05 μm in the focal cystoid group and 401.03±75.1 μm in the neurosensory detachment group. A mean of 2.05 (range:1-5) injections in the focal group, 1.32 (range:1-2) in the diffuse group, 2.6 (range:1-6) in the focal cystoid group and 2.6 (range:1-6) in the neurosensory detachment group were performed during the six month follow-up period. Following intravitreal bevacizumab treatment, vision improved, remained unchanged or worsened in 11, 7 and 2 subjects in focal group; 11, 9 and 8 in diffuse group; 0, 2 and 4 in focal cystoid group and 5, 5 and 3 subjects respectively in neurosensory detachment group.<b>CONCLUSION:</b>OCT morpholgy patterns in DME may predict the effects of intravitreal bevacizumab treatment, and patients with focal DME are most likely to benefit from the improvent of visual acuity from this treatment

Clinical and genetic delineation of autosomal recessive and dominant ACTL6B-related developmental brain disorders

Purpose: This study aims to comprehensively delineate the phenotypic spectrum of ACTL6B-related disorders, previously associated with both autosomal recessive and autosomal dominant neurodevelopmental disorders. Molecularly, the role of the nucleolar protein ACTL6B in contributing to the disease has remained unclear. Methods: We identified 105 affected individuals, including 39 previously reported cases, and systematically analyzed detailed clinical and genetic data for all individuals. Additionally, we conducted knockdown experiments in neuronal cells to investigate the role of ACTL6B in ribosome biogenesis. Results: Biallelic variants in ACTL6B are associated with severe-to-profound global developmental delay/intellectual disability, infantile intractable seizures, absent speech, autistic features, dystonia, and increased lethality. De novo monoallelic variants result in moderate-to-severe global developmental delay/intellectual disability, absent speech, and autistic features, whereas seizures and dystonia were less frequently observed. Dysmorphic facial features and brain abnormalities, including hypoplastic corpus callosum, and parenchymal volume loss/atrophy, are common findings in both groups. We reveal that in the nucleolus, ACTL6B plays a crucial role in ribosome biogenesis, particularly in pre-rRNA processing. Conclusion: This study provides a comprehensive characterization of the clinical spectrum of both autosomal recessive and dominant forms of ACTL6B-associated disorders. It offers a comparative analysis of their respective phenotypes provides a plausible molecular explanation and suggests their inclusion within the expanding category of “ribosomopathies.”<p/

Clinical and genetic delineation of autosomal recessive and dominant ACTL6B-related developmental brain disorders.

PURPOSE: This study aims to comprehensively delineate the phenotypic spectrum of ACTL6B-related disorders, previously associated with both autosomal recessive and autosomal dominant neurodevelopmental disorders. Molecularly, the role of the nucleolar protein ACTL6B in contributing to the disease has remained unclear. METHODS: We identified 105 affected individuals, including 39 previously reported cases, and systematically analysed detailed clinical and genetic data for all individuals. Additionally, we conducted knockdown experiments in neuronal cells to investigate the role of ACTL6B in ribosome biogenesis. RESULTS: Biallelic variants in ACTL6B are associated with severe-to-profound global developmental delay/intellectual disability (GDD/ID), infantile intractable seizures, absent speech, autistic features, dystonia, and increased lethality. De novo monoallelic variants result in moderate-to-severe GDD/ID, absent speech, and autistic features, while seizures and dystonia were less frequently observed. Dysmorphic facial features and brain abnormalities, including hypoplastic corpus callosum, parenchymal volume loss/atrophy, are common findings in both groups. We reveal that in the nucleolus, ACTL6B plays a crucial role in ribosome biogenesis, in particular in pre-rRNA processing. CONCLUSION: This study provides a comprehensive characterization of the clinical spectrum of both autosomal recessive and dominant forms of ACTL6B-associated disorders. It offers a comparative analysis of their respective phenotypes provides a plausible molecular explanation and suggests their inclusion within the expanding category of 'ribosomopathies'

Evaluation of prognostic risk models for postoperative pulmonary complications in adult patients undergoing major abdominal surgery: a systematic review and international external validation cohort study

Background Stratifying risk of postoperative pulmonary complications after major abdominal surgery allows clinicians to modify risk through targeted interventions and enhanced monitoring. In this study, we aimed to identify and validate prognostic models against a new consensus definition of postoperative pulmonary complications. Methods We did a systematic review and international external validation cohort study. The systematic review was done in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched MEDLINE and Embase on March 1, 2020, for articles published in English that reported on risk prediction models for postoperative pulmonary complications following abdominal surgery. External validation of existing models was done within a prospective international cohort study of adult patients (≥18 years) undergoing major abdominal surgery. Data were collected between Jan 1, 2019, and April 30, 2019, in the UK, Ireland, and Australia. Discriminative ability and prognostic accuracy summary statistics were compared between models for the 30-day postoperative pulmonary complication rate as defined by the Standardised Endpoints in Perioperative Medicine Core Outcome Measures in Perioperative and Anaesthetic Care (StEP-COMPAC). Model performance was compared using the area under the receiver operating characteristic curve (AUROCC). Findings In total, we identified 2903 records from our literature search; of which, 2514 (86·6%) unique records were screened, 121 (4·8%) of 2514 full texts were assessed for eligibility, and 29 unique prognostic models were identified. Nine (31·0%) of 29 models had score development reported only, 19 (65·5%) had undergone internal validation, and only four (13·8%) had been externally validated. Data to validate six eligible models were collected in the international external validation cohort study. Data from 11 591 patients were available, with an overall postoperative pulmonary complication rate of 7·8% (n=903). None of the six models showed good discrimination (defined as AUROCC ≥0·70) for identifying postoperative pulmonary complications, with the Assess Respiratory Risk in Surgical Patients in Catalonia score showing the best discrimination (AUROCC 0·700 [95% CI 0·683–0·717]). Interpretation In the pre-COVID-19 pandemic data, variability in the risk of pulmonary complications (StEP-COMPAC definition) following major abdominal surgery was poorly described by existing prognostication tools. To improve surgical safety during the COVID-19 pandemic recovery and beyond, novel risk stratification tools are required. Funding British Journal of Surgery Society

Corneal collagen crosslinking for progressive keratoconus in Saudi Arabia: One-year controlled clinical trial analysis

AbstractAimsTo determine the short-term efficacy of corneal collagen crosslinking (CXL) treatment in patients with progressive Keratoconus (KCN) in comparison with no treatment.Settings and designThis controlled clinical trial study was carried out at a tertiary eye hospital, Eastern Province, Saudi Arabia.Methods and materialA prospective controlled clinical study of patients being treated for Keratoconus at a tertiary eye care hospital in the Eastern province of Saudi Arabia. 51 eyes of 43 patients with progressive KCN who received corneal collagen crosslinking (treatment group) and 50 eyes of 34 patients with KCN and no treatment (control group) were included in our study. A one year clinical data were collected preoperatively as well as at 1, 3, 6 and 12months postoperatively for the treatment group patients. A baseline and 1year clinical data were collected for the control group patients. The short-term efficacy of the treatment in preventing progression of KCN in comparison with no treatment was analysed at one year.ResultsAt one year after crosslinking there was significant flattening of the average keratometry by 0.61D (p=0.001) [95% CI: 0.25, 0.97] compared to 0.40D (p=0.210) steepening in the control group; difference between treatment and control was 1.01D (p=0.006) [95%CI: 0.29, 1.72]. Pachymetry in treatment group thinned by 20.21μm (p<0.0001) [95% CI: 12.77, 27.66] compared to 0.32μm (p=0.912) in the control group. Visual acuity remained stable at the preoperative level of 20/30 (p=0.397) in the treatment group and 20/40 (p=0.553) in the control group at one year.ConclusionsCorneal CXL is an effective treatment for halting the progression of KCN as shown by reduced keratometry and stability of vision