Neonatal adrenal haemorrhage with contralateral scrotal haematoma and inguinal ecchymosis.

Neonatal adrenal haemorrhage (NAH) is more frequently described in neonates due to their relatively larger size and increased vascularity. While most are asymptomatic, they can present with anaemia, jaundice, abdominal mass, scrotal haematoma or more severe complications such as shock and adrenal insufficiency. Scrotal haematoma seen with NAH may be mistaken for other more serious conditions causing acute scrotum. Prompt sonographic examination that includes the bilateral adrenal glands may help to detect NAH early and to avoid unnecessary interventions. Cases of NAH causing ipsilateral inguinal ecchymosis and scrotal haematoma have been reported, but contralateral haematomas are very rare. In this report, we present a unique case of a neonate with an antenatally acquired adrenal haematoma complicated with an acute peripartum rebleeding manifesting as a contralateral scrotal haematoma and inguinal ecchymosis. The NAH was treated conservatively and resolved on follow-up imaging.

Isolated unilateral hypoglossal nerve palsy from suppurative retropharyngeal lymphadenitis in an infant.

Retropharyngeal infections (RPIs) are uncommon in young infants and are difficult to diagnose due to their non-classical presentation. RPI can occasionally be complicated with multiple cranial nerve palsies but rarely in isolation. Isolated hypoglossal nerve palsy (HNP) due to RPI has been described in the literature but mostly in older children and adults. Assessment for hypoglossal nerve function is challenging in a young infant because the conventional signs of hypoglossal nerve dysfunction are difficult to elicit in this age group. Early recognition and treatment of RPI are associated with good HNP recovery. We present a case of a young infant with tongue deviation and difficulty with feeding attributed to an isolated HNP caused by suppurative retropharyngeal lymphadenitis. The infant underwent incision and drainage with complete recovery of the tongue function after 8 weeks.

Cosmetic Contact Lenses in the United Kingdom: Assessment of Online Regulation and Quality of Consumer Health Information.

OBJECTIVES: To determine the compliance of online vendors to the UK Opticians Act 1989 Section 27 requirements and safety regulations for cosmetic contact lens (CCL) sales and the quality of online CCL health information. METHODS: The top 50 websites selling CCLs on each three search engines, namely Google, Yahoo, and Bing, were selected. Duplicates were removed, and the remaining websites were systematically analyzed in February 2023. UK legal authorization for CCL sales was assessed using the Opticians Act Section 27 and safety regulations determined by the presence of Conformité Européene (CE) marking. The quality and reliability of online information was graded using the DISCERN (16-80) and JAMA (0-4) scores by two independent reviewers. RESULTS: Forty-seven eligible websites were analyzed. Only six (12.7%) met the UK legal authorization for CCL sales. Forty-nine different brands of CCLs were sold on these websites, of which 13 (26.5%) had no CE marking. The mean DISCERN and JAMA benchmark scores were 26 ± 12.2 and 1.3 ± 0.6, respectively (intraclass correlation scores: 0.99 for both). CONCLUSIONS: A significant number of websites provide consumers with easy, unsafe, and unregulated access to CCLs. Most online stores do not meet the requirements set out in the Opticians Act for CCL sales in the United Kingdom. A significant number of CCLs lack CE marking, while the average quality of information on websites selling CCLs is poor. Together, these pose a risk to consumers purchasing CCLs from unregulated websites, and therefore, further stringent regulations on the online sales of these products are needed.

Real-World Data on Faricimab Switching in Treatment-Refractory Neovascular Age-Related Macular Degeneration.

Faricimab is a newly approved bispecific antibody for neovascular age-related macular degeneration (nAMD). Our study aims to evaluate clinical outcomes of faricimab switching in patients with treatment-refractory nAMD; determine parameters that predict these outcomes; and obtain patient subjective experience on this new injection. This is a retrospective case review with clinical and imaging data from a tertiary referral unit (Birmingham and Midland Eye Centre, UK), involving patients who were switched to faricimab between 1 January and 1 December 2023. In all, 63 eyes (54 patients) with a mean age of 79.2 ± 7.8 and mean of 41.5 ± 22.4 previous anti-VEGF injections were analysed. With a mean of 4.81 ± 1.16 faricimab injections over 6.98 ± 1.75 months, post-treatment visual acuity was logMAR 0.49 ± 0.36 and central macular thickness (CMT) was 320.3 ± 97.9 µm. After first dose, 39.1% achieved complete dryness and 89.1% had anatomical improvement. Presence of subretinal fluid was a predictor of better functional outcomes (p = 0.001, ß = -0.182), while initial CMT predicted better anatomical outcomes (p = 0.001, ß = 0.688). Compared to their experiences of previous anti-VEGF injections, 89% of patients reported no more discomfort and 87.0% experienced no more floaters, photopsia, or bubbles post-injection. Faricimab switching has anatomical efficacy but limited functional improvement in treatment-refractory AMD. Patient experiences of faricimab compared to previous injections were overall positive.

Concordance of randomised controlled trials for artificial intelligence interventions with the CONSORT-AI reporting guidelines.

The Consolidated Standards of Reporting Trials extension for Artificial Intelligence interventions (CONSORT-AI) was published in September 2020. Since its publication, several randomised controlled trials (RCTs) of AI interventions have been published but their completeness and transparency of reporting is unknown. This systematic review assesses the completeness of reporting of AI RCTs following publication of CONSORT-AI and provides a comprehensive summary of RCTs published in recent years. 65 RCTs were identified, mostly conducted in China (37%) and USA (18%). Median concordance with CONSORT-AI reporting was 90% (IQR 77-94%), although only 10 RCTs explicitly reported its use. Several items were consistently under-reported, including algorithm version, accessibility of the AI intervention or code, and references to a study protocol. Only 3 of 52 included journals explicitly endorsed or mandated CONSORT-AI. Despite a generally high concordance amongst recent AI RCTs, some AI-specific considerations remain systematically poorly reported. Further encouragement of CONSORT-AI adoption by journals and funders may enable more complete adoption of the full CONSORT-AI guidelines.

Ocular Metastasis as First Presentation of Large-Cell Neuroendocrine Carcinoma.

Introduction: We report a rare case of an aggressive large-cell neuroendocrine lung tumour, which presented with ocular metastasis. Case Presentation: A 70-year-old lady presented with a 4-week history of left eye pain and photophobia. Ocular examination revealed left-sided episcleritis and she was treated with topical lubricants and steroids. However, she re-presented 6 months later with recurrent left eye symptoms and was found to have an iris stroma amelanotic lesion, posterior synechiae, 360-degrees rubeosis iridis, raised intraocular pressure, and trace vitreous inflammation. Ultrasound biomicroscopy revealed a left thickened iris with an associated ciliary body lesion. Sarcoid-related ocular inflammation was suspected, but a computed tomography (CT) scan of the lung revealed an incidental right upper lobe lesion. Histology from a transcorneal iris biopsy showed a high-grade neuroendocrine carcinoma, and the diagnosis of metastatic lung large-cell neuroendocrine carcinoma was confirmed via high-resolution CT scan, positron emission tomography scan, and CT-guided lung biopsy. She was given multiple courses of different chemotherapy regimens along with palliative radiotherapy. However, the tumour and its metastases continued to progress and she passed away 4 years after her initial presentation. Conclusion: Ocular metastatic large-cell neuroendocrine carcinoma is rare, and the first presentation with ocular metastasis is even rarer. This case highlights the importance of early detection of ocular metastases in order to hasten oncological treatment. A low threshold for systemic investigations and ophthalmology referral in cases of unexplained, refractory ocular symptomatology is essential, given the heterogeneous presentation, rarity, and poor prognosis of these tumours, even with maximal treatment.

Differential effects of prenatal psychological distress and positive mental health on offspring socioemotional development from infancy to adolescence: a meta-analysis.

The impact of prenatal maternal mental health on offspring socioemotional development is substantial and enduring. Existing literature primarily focuses on the effects of psychological distress during pregnancy, emphasizing adverse child outcomes. Recent studies, however, highlight the unique impact of positive maternal mental health on child outcomes. To elucidate the differential associations of maternal psychological distress and positive mental health during pregnancy with child outcomes, we conducted a systematic literature search and random-effects meta-analyses on studies investigating the associations of prenatal maternal mental health with child socioemotional development. Our analyses, comprising 74 studies with 321,966 mother-child dyads across 21 countries, revealed significant associations of prenatal psychological distress with both adverse and positive child socioemotional outcomes. Notably, the effect sizes for the association of psychological distress with positive child outcomes were smaller compared to adverse outcomes. Positive prenatal mental health, on the other hand, was significantly associated with positive socioemotional outcomes but not adverse outcomes. This meta-analysis highlights the independence of negative and positive prenatal mental health constructs and their distinct relationships with child socioemotional development. The findings underscore the importance of considering the positive spectrum of maternal mental health and developmental outcomes to enhance our understanding of prenatal influences on child development. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=335227, identifier CRD42022335227.

Diagnosis of Acanthamoeba Keratitis: Past, Present and Future.

Acanthamoeba keratitis (AK) is a painful and sight-threatening parasitic corneal infection. In recent years, the incidence of AK has increased. Timely and accurate diagnosis is crucial during the management of AK, as delayed diagnosis often results in poor clinical outcomes. Currently, AK diagnosis is primarily achieved through a combination of clinical suspicion, microbiological investigations and corneal imaging. Historically, corneal scraping for microbiological culture has been considered to be the gold standard. Despite its technical ease, accessibility and cost-effectiveness, the long diagnostic turnaround time and variably low sensitivity of microbiological culture limit its use as a sole diagnostic test for AK in clinical practice. In this review, we aim to provide a comprehensive overview of the diagnostic modalities that are currently used to diagnose AK, including microscopy with staining, culture, corneal biopsy, in vivo confocal microscopy, polymerase chain reaction and anterior segment optical coherence tomography. We also highlight emerging techniques, such as next-generation sequencing and artificial intelligence-assisted models, which have the potential to transform the diagnostic landscape of AK.

Image projective transformation rectification with synthetic data for smartphone-captured chest X-ray photos classification.

Automatic interpretation of chest X-ray (CXR) photos taken by smartphones at the same performance level as with digital CXRs is challenging, due to the projective transformation caused by the non-ideal camera position. Existing rectification methods for other camera-captured photos (document photos, license plate photos, etc.) cannot precisely rectify the projective transformation of CXR photos, due to its specific projective transformation type. In this paper, we propose an innovative deep learning-based Projective Transformation Rectification Network (PTRN) to automatically rectify the projective transformation of CXR photos by predicting the projective transformation matrix. Additionally, synthetic CXR photos are generated for training with the consideration of visual artifacts of natural images. The effectiveness of the proposed classification pipeline with PTRN is evaluated in the CheXphoto smartphone-captured CXR photo classification competition. It achieves first place with a huge performance improvement (ours 0.850, second-best 0.762, in AUC). Moreover, experimental results show that our approach successfully achieves the same performance level of digital CXR classification (AUC 0.893) on CXR photo classification (AUC 0.893).

IL11 (Interleukin-11) Causes Emphysematous Lung Disease in a Mouse Model of Marfan Syndrome.

BACKGROUND: Marfan Syndrome (MFS) is an inherited connective tissue disorder caused by mutations in the FBN1 (fibrillin-1) gene. Lung abnormalities are common in MFS, but their pathogenesis is poorly understood. IL11 (interleukin-11) causes aortic disease in a mouse model of MFS and was studied here in the lung. METHODS: We examined histological and molecular phenotypes in the lungs of Fbn1C1041G/+ mice (mouse model of Marfan Syndrome [mMFS]), an established mouse model of MFS. To identify IL11-expressing cells, we used immunohistochemistry on lungs of 4- and 16-week-old Fbn1C1041G/+:Il11EGFP/+ reporter mice. We studied the effects of IL11 inhibition by RT-qPCR, immunoblots and histopathology in lungs from genetic or pharmacologic models: (1) 16-week-old IL11 receptor (IL11RA) knockout mMFS mice (Fbn1C1041G/+:Il11ra1-/- mice) and (2) in mMFS mice administered IgG control or interleukin-11 receptor antibodies twice weekly from 4 to 24 weeks of age. RESULTS: mMFS lungs showed progressive loss and enlargement of distal airspaces associated with increased proinflammatory and profibrotic gene expression as well as matrix metalloproteinases 2, 9, and 12. IL11 was increased in mMFS lungs and localized to smooth muscle and endothelial cells in young mMFS mice in the Fbn1C1041G/+:Il11EGFP/+ reporter strain and in fibroblasts, in older mice. In mMFS mice, genetic (Fbn1C1041G/+:Il11ra1-/-) or pharmacologic (anti-interleukin-11 receptor) inhibition of IL11 signaling reduced lung emphysema, fibrosis, and inflammation. This protective effect was associated with reduced pathogenic ERK1/2 signaling and lower metalloproteinase 2, 9, and 12 expression. CONCLUSIONS: IL11 causes lung disease in mMFS. This reveals a shared IL11-driven disease mechanism in lung and aorta in MFS and suggests inhibition of IL11 signaling as a holistic approach for treating multiorgan morbidity in MFS.

Energy-Efficient Cooperative Spectrum Sensing Using Machine Learning Algorithm.

Cognitive Radio (CR) is a practical technique for overcoming spectrum inefficiencies by sensing and utilizing spectrum holes over a wide spectrum. In particular, cooperative spectrum sensing (CSS) determines the state of primary users (PUs) by cooperating with multiple secondary users (SUs) distributed around a Cognitive Radio Network (CRN), further overcoming various noise and fading issues in the radio environment. But it's still challenging to balance energy efficiency and good sensing performances in the existing CSS system, especially when the CRN consists of battery-limited sensors. This article investigates the application of machine learning technologies for cooperative spectrum sensing, especially through solving a multi-dimensional optimization that cannot be readily addressed by traditional approaches. Specifically, we develop a neural network, which involves parameters that are integral to the CSS performance, including a device sleeping rate for each sensor and thresholds used in the energy detection method, and a customized loss function based on the energy consumption of the CSS system and multiple penalty terms reflecting the system requirements. Using this formulation, energy consumption is to be minimized with the guarantee of reaching a certain probability of false alarm and detection in the CSS system. With the proposed method, comparison studies under different hard fusion rules ('OR' and 'AND') demonstrate its effectiveness in improving the CSS system performances, as well as its robustness in the face of changing global requirements. This paper also suggests the combination of the traditional and the proposed scheme to circumvent the respective inherent pitfalls of neural networks and the traditional semi-analytic methods.

Sterile endogenous panophthalmitis with uncontrolled diabetes.

A female patient with type 2 diabetes in her 50s presented to casualty with a 1-day history of red, painful right eye. Visual acuity (VA) bilaterally was 6/12, but a right anterior uveitis was noted, with hazy fundal view. She was discharged on topical steroid and mydriatic drops with a 2-day follow-up. VA remained unchanged, but she developed right proptosis, restricted eye movements, lid swelling, relative afferent pupillary defect and an intraocular pressure (IOP) of 39 mm Hg. She was admitted and treated with intravenous and intravitreal antibiotics, intravenous antifungals and IOP-lowering drugs. Blood tests showed raised inflammatory markers and an HbA1c of 127 mmol/mol. Over her admission, right eye vision deteriorated to no light perception. A B-scan ultrasound revealed panophthalmitis and a retinal abscess. All investigations looking for a source were negative. Inflammatory markers settled, but despite aggressive treatment, the panophthalmitis did not improve. She was discharged with a follow-up to consider enucleation.

Reversal of collateral ventilation using endoscopic polymer foam in COPD patients undergoing endoscopic lung volume reduction with endobronchial valves: A controlled parallel group trial.

BACKGROUND AND OBJECTIVE: We have previously described reversal of collateral ventilation (CV) in a severe chronic obstructive pulmonary disease (COPD) patient with endoscopic polymer foam (EPF), prior to endoscopic lung volume reduction (ELVR) with valves. The aim of this study was to investigate the efficacy of this in a larger cohort and compare outcomes with a similar cohort with no CV. METHODS: Patients with severe COPD, with the left upper lobe (LUL) targeted for ELVR, were assessed for CV with high resolution computed tomography (HRCT). If fissure completeness was >95% they were enrolled as controls for valves alone (endobronchial valve control group [EBV-CTRL]). If fissure completeness was 80%-95%, defects were mapped to the corresponding segment, where EPF was instilled following confirmation of CV with CHARTIS. EBVs were inserted 1 month afterwards. RESULTS: Fourteen patients were enrolled into both arms. After 6 months, there were significant improvements in both groups in forced expiratory volume in 1 s (FEV1; +19.7% EPF vs. +27.7% EBV-CTRL, p < 0.05); residual volume (RV; -16.2% EPF vs. -20.1% EBV-CTRL, p = NS); SGRQ (-15.1 EPF vs. -16.6 EBV-CTRL p = NS) and 6 min walk (+25.8% EPF [77.2 m] vs. +28.4% [82.3 m] EBV-CTRL p = NS). Patients with fissural defects mapped to the lingula had better outcomes than those mapped to other segments (FEV1 +22.9% vs. +16.3% p < 0.05). There were no serious adverse reactions to EPF. CONCLUSION: EPF successfully reverses CV in severe COPD patients with a left oblique fissure that is 80%-95% complete. Following EBV, outcomes are similar to patients with complete fissures undergoing ELVR with EBV alone. EPF therapy to reverse CV potentially increases the number of COPD patients suitable for ELVR with minimal adverse reactions.

Interleukin-11: A Potential Biomarker and Molecular Therapeutic Target in Non-Small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer and is a fast progressive disease when left untreated. Identification of potential biomarkers in NSCLC is an ongoing area of research that aims to detect, diagnose, and prognosticate patients early to optimize treatment. We review the role of interleukin-11 (IL11), a stromal-cell derived pleiotropic cytokine with profibrotic and cellular remodeling properties, as a potential biomarker in NSCLC. This review identifies the need for biomarkers in NSCLC, the potential sources of IL11, and summarizes the available information leveraging upon published literature, publicly available datasets, and online tools. We identify accumulating evidence suggesting IL11 to be a potential biomarker in NSCLC patients. Further in-depth studies into the pathophysiological effects of IL11 on stromal-tumor interaction in NSCLC are warranted and current available literature highlights the potential value of IL11 detection as a diagnostic and prognostic biomarker in NSCLC.

Neurological Waardenburg-Shah syndrome: a diagnostic challenge in a child with skin hypopigmentation and neurological manifestation.

Peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome and Hirschsprung disease (PCWH) is a rare manifestation of Waardenburg-Shah syndrome associated with mutations in the SOX10 gene. The phenotypic expression is variable, thus presenting a diagnostic challenge. Clinical manifestations of PCWH may mimic other neurocutaneous syndromes. A thorough history, careful physical examination, appropriate imaging studies and an index of suspicion are needed to diagnose this condition. We describe an adolescent girl with skin hypopigmentation and blue irides associated with sensorineural hearing loss, Hirschsprung disease, as well as seizures with neurological signs, and discuss the challenges in diagnosing PCWH.

Increased variability of the western Pacific subtropical high under greenhouse warming.

SignificanceThe western Pacific subtropical high (WPSH) channels moisture from the tropics that underpins the East Asian summer climate. Interannual variability of the WPSH dominates climate extremes in the densely populated countries of East Asia. In 2020, an anomalously strong WPSH led to catastrophic floods with hundreds of deaths, 28,000 homes destroyed, and tens of billions in economic damage in China alone. How the frequency of such strong WPSH events will change is of great societal concern. Our finding of an increase in future WPSH variability, translating into an increased frequency of climate extreme as seen in the 2020 episode, highlights the increased risks for the billions of people in the densely populated East Asia with profound socioeconomic consequences.

IL11 Activates Pancreatic Stellate Cells and Causes Pancreatic Inflammation, Fibrosis and Atrophy in a Mouse Model of Pancreatitis.

Interleukin-11 (IL11) is important for fibrosis and inflammation, but its role in the pancreas is unclear. In pancreatitis, fibrosis, inflammation and organ dysfunction are associated with pancreatic stellate cell (PSC)-to-myofibroblast transformation. Here, we show that IL11 stimulation of PSCs, which specifically express IL11RA in the pancreas, results in transient STAT3 phosphorylation, sustained ERK activation and PSC activation. In contrast, IL6 stimulation of PSCs caused sustained STAT3 phosphorylation but did not result in ERK activation or PSC transformation. Pancreatitis factors, including TGFß, CTGF and PDGF, induced IL11 secretion from PSCs and a neutralising IL11RA antibody prevented PSC activation by these stimuli. This revealed an important ERK-dependent role for autocrine IL11 activity in PSCs. In mice, IL11 was increased in the pancreas after pancreatic duct ligation, and in humans, IL11 and IL11RA levels were elevated in chronic pancreatitis. Following pancreatic duct ligation, administration of anti-IL11RA to mice reduced pathologic (ERK, STAT, NF-κB) signalling, pancreatic atrophy, fibrosis and pro-inflammatory cytokine (TNFα, IL6 and IL1ß) levels. This is the first description of IL11-mediated activation of PSCs, and the data suggest IL11 as a stromal therapeutic target in pancreatitis.

Investigation of Cas9 antibodies in the human eye.

Preexisting immunity against Cas9 proteins in humans represents a safety risk for CRISPR-Cas9 technologies. However, it is unclear to what extent preexisting Cas9 immunity is relevant to the eye as it is targeted for early in vivo CRISPR-Cas9 clinical trials. While the eye lacks T-cells, it contains antibodies, cytokines, and resident immune cells. Although precise mechanisms are unclear, intraocular inflammation remains a major cause of vision loss. Here, we used immunoglobulin isotyping and ELISA platforms to profile antibodies in serum and vitreous fluid biopsies from human adult subjects and Cas9-immunized mice. We observed high prevalence of preexisting Cas9-reactive antibodies in serum but not in the eye. However, we detected intraocular antibodies reactive to S. pyogenes-derived Cas9 after S. pyogenes intraocular infection. Our data suggest that serum antibody concentration may determine whether specific intraocular antibodies develop, but preexisting immunity to Cas9 may represent a lower risk in human eyes than systemically.

Inhibition of IL11 Signaling Reduces Aortic Pathology in Murine Marfan Syndrome.

BACKGROUND: Marfan syndrome (MFS) is associated with TGF (transforming growth factor) ß-stimulated ERK (extracellular signal-regulated kinase) activity in vascular smooth muscle cells (VSMCs), which adopt a mixed synthetic/contractile phenotype. In VSMCs, TGFß induces IL (interleukin) 11) that stimulates ERK-dependent secretion of collagens and MMPs (matrix metalloproteinases). Here, we examined the role of IL11 in the MFS aorta. METHODS: We used echocardiography, histology, immunostaining, and biochemical methods to study aortic anatomy, physiology, and molecular endophenotypes in Fbn1C1041G/+ mice, an established murine model of MFS (mMFS). mMFS mice were crossed to an IL11-tagged EGFP (enhanced green fluorescent protein; Il11EGFP/+) reporter strain or to a strain deleted for the IL11 receptor (Il11ra1-/-). In therapeutic studies, mMFS were administered an X209 (neutralizing antibody against IL11RA [IL11 receptor subunit alpha]) or IgG for 20 weeks and imaged longitudinally. RESULTS: IL11 mRNA and protein were elevated in the aortas of mMFS mice, as compared to controls. mMFS mice crossed to Il11EGFP/+ mice had increased IL11 expression in VSMCs, notably in the aortic root and ascending aorta. As compared to the mMFS parental strain, double mutant mMFS:Il11ra1-/- mice had reduced aortic dilatation and exhibited lesser fibrosis, inflammation, elastin breaks, and VSMC loss, which was associated with reduced aortic COL1A1 (collagen type I alpha 1 chain), IL11, MMP2/9, and phospho-ERK expression. To explore therapeutic targeting of IL11 signaling in MFS, we administered either a neutralizing antibody against IL11RA (X209) or an IgG control. After 20 weeks of antibody administration, as compared to IgG, mMFS mice receiving X209 had reduced thoracic and abdominal aortic dilation as well as lesser fibrosis, inflammation, elastin breaks, and VSMC loss. By immunoblotting, X209 was shown to reduce aortic COL1A1, IL11, MMP2/9, and phospho-ERK expression. CONCLUSIONS: In MFS, IL11 is upregulated in aortic VSMCs to cause ERK-related thoracic aortic dilatation, inflammation, and fibrosis. Therapeutic inhibition of IL11, imminent in clinical trials, might be considered as a new approach in MFS.