A missense variant in SLC12A3 gene enhances aberrant splicing causing Gitelman syndrome.

Gitelman syndrome (GS) is the most prevalent genetic tubulopathy characterized by several electrolyte abnormalities, including hypokalemia, hypomagnesemia, hypocalciuria, metabolic alkalosis, and hyperreninemic hyperaldosteronism. These features are caused by a bi-allelic mutation in the SLC12A3 gene. In this report, we present a case of GS in an asymptomatic woman who incidentally exhibited hypokalemia during an antenatal check-up. Her biochemical profile was consistent with GS. Genetic analysis revealed two heterozygous variants in trans, namely, NM_001126108.2:c.625C>T; p.(Arg209Trp) and c.965C>T; p.(Ala322Val). The c.625C>T; p.(Arg209Trp) variant has previously been experimentally confirmed as a loss-of-function (LOF) variant. However, the functional impact of the c.965C>T variant, located at the 5 prime end of exon 8, has not been fully elucidated. Through the utilization of both complementary DNA (cDNA) and minigene analysis, we confirmed that the c.965C>T variant can generate two distinct cDNA transcripts. The first transcript carries a missense mutation, p.(Ala322Val) in the full SLC12A3 transcript, while the second transcript consists of an in-frame deletion of both exons 7 and 8 in the SLC12A3 transcript, in which may result in the loss of transmembrane regions 5 - 6 involved in chloride transport. Our findings provide insights into the intricate mechanisms of splicing, highlighting how a variant in one exon can remotely influence the transcription of an upstream exon, as observed with the variant in exon 8 impacting the transcription of exon 7.

SERS-Based Droplet Microfluidic Platform for Sensitive and High-Throughput Detection of Cancer Exosomes.

Exosomes, nanosized extracellular vesicles containing biomolecular cargo, are increasingly recognized as promising noninvasive biomarkers for cancer diagnosis, particularly for their role in carrying tumor-specific molecular information. Traditional methods for exosome detection face challenges such as complexity, time consumption, and the need for sophisticated equipment. This study addresses these challenges by introducing a novel droplet microfluidic platform integrated with a surface-enhanced Raman spectroscopy (SERS)-based aptasensor for the rapid and sensitive detection of HER2-positive exosomes from breast cancer cells. Our approach utilized an on-chip salt-induced gold nanoparticles (GNPs) aggregation process in the presence of HER2 aptamers and HER2-positive exosomes, enhancing the hot spot-based SERS signal amplification. This platform achieved a limit of detection of 4.5 log10 particles/mL with a sample-to-result time of 5 min per sample. Moreover, this platform has been successfully applied for HER2 status testing in clinical samples to distinguish HER2-positive breast cancer patients from HER2-negative breast cancer patients. High sensitivity, specificity, and the potential for high-throughput screening of specific tumor exosomes make this SERS-based droplet system a potential liquid biopsy technology for early cancer diagnosis.

Familial thrombotic microangiopathy in a child with coenzyme Q10 deficiency-associated glomerulopathy.

We report a child with biallelic COQ6 variants presenting with familial thrombotic microangiopathy (TMA). A Chinese boy presented with steroid-resistant nephrotic syndrome at 8 months old and went into kidney failure requiring peritoneal dialysis at 15 months old. He presented with hypertensive encephalopathy with the triad of microangiopathic haemolytic anaemia, thrombocytopenia, and acute on chronic kidney injury at 25 months old following a viral illness. Kidney biopsy showed features of chronic TMA. He was managed with supportive therapy and plasma exchanges and maintained on eculizumab. However, he had another TMA relapse despite complement inhibition a year later. Eculizumab was withdrawn, and supportive therapies, including ubiquinol (50 mg/kg/day) and vitamins, were optimized. He remained relapse-free since then for 4 years. Of note, his elder sister succumbed to multiple organ failure with histological evidence of chronic TMA at the age of 4. Retrospective genetic analysis revealed the same compound heterozygous variants in the COQ6 gene.

Comprehensive Review of COVID-19: Epidemiology, Pathogenesis, Advancement in Diagnostic and Detection Techniques, and Post-Pandemic Treatment Strategies.

At present, COVID-19 remains a public health concern due to the ongoing evolution of SARS-CoV-2 and its prevalence in particular countries. This paper provides an updated overview of the epidemiology and pathogenesis of COVID-19, with a focus on the emergence of SARS-CoV-2 variants and the phenomenon known as 'long COVID'. Meanwhile, diagnostic and detection advances will be mentioned. Though many inventions have been made to combat the COVID-19 pandemic, some outstanding ones include multiplex RT-PCR, which can be used for accurate diagnosis of SARS-CoV-2 infection. ELISA-based antigen tests also appear to be potential diagnostic tools to be available in the future. This paper also discusses current treatments, vaccination strategies, as well as emerging cell-based therapies for SARS-CoV-2 infection. The ongoing evolution of SARS-CoV-2 underscores the necessity for us to continuously update scientific understanding and treatments for it.

Signal amplification by cyclic extension enables high-sensitivity single-cell mass cytometry.

Mass cytometry uses metal-isotope-tagged antibodies to label targets of interest, which enables simultaneous measurements of ~50 proteins or protein modifications in millions of single cells, but its sensitivity is limited. Here, we present a signal amplification technology, termed Amplification by Cyclic Extension (ACE), implementing thermal-cycling-based DNA in situ concatenation in combination with 3-cyanovinylcarbazole phosphoramidite-based DNA crosslinking to enable signal amplification simultaneously on >30 protein epitopes. We demonstrate the utility of ACE in low-abundance protein quantification with suspension mass cytometry to characterize molecular reprogramming during the epithelial-to-mesenchymal transition as well as the mesenchymal-to-epithelial transition. We show the capability of ACE to quantify the dynamics of signaling network responses in human T lymphocytes. We further present the application of ACE in imaging mass cytometry-based multiparametric tissue imaging to identify tissue compartments and profile spatial aspects related to pathological states in polycystic kidney tissues.

An Aggregation-Induced Emission-Based Dual Emitting Nanoprobe for Detecting Intracellular pH and Unravelling Metabolic Variations in Differentiating Lymphocytes.

Monitoring T lymphocyte differentiation is essential for understanding T cell fate regulation and advancing adoptive T cell immunotherapy. However, current biomarker analysis methods necessitate cell lysis, leading to source depletion. Intracellular pH (pHi) can be affected by the presence of lactic acid (LA), a metabolic mediator of T cell activity such as glycolysis during T cell activation; therefore, it is a potentially a good biomarker of T cell state. In this work, a dual emitting enhancement-based nanoprobe, namely, AIEgen@F127-AptCD8, was developed to accurately detect the pHi of T cells to "read" the T cell differentiation process. The nanocore of this probe comprises a pair of AIE dyes, TPE-AMC (pH-sensitive moiety) and TPE-TCF, that form a donor-acceptor pair for sensitive detection of pHi by dual emitting enhancement analysis. The nanoprobe exhibits a distinctly sensitive narrow range of pHi values (from 6.0 to 7.4) that can precisely distinguish the differentiated lymphocytes from naïve ones based on their distinct pHi profiles. Activated CD8+ T cells demonstrate lower pHi (6.49 ± 0.09) than the naïve cells (7.26 ± 0.11); Jurkat cells exhibit lower pHi (6.43 ± 0.06) compared to that of nonactivated ones (7.29 ± 0.09) on 7 days post-activation. The glycolytic product profiles in T cells strongly correlate with their pHi profiles, ascertaining the reliability of probing pHi for predicting T cell states. The specificity and dynamic detection capabilities of this nanoprobe make it a promising tool for indirectly and noninvasively monitoring T cell activation and differentiation states.

Computer-assisted patient identification tool in inborn errors of metabolism - potential for rare disease patient registry and big data analysis.

BACKGROUND: Patient registries are crucial for rare disease management. However, manual registry construction is labor-intensive and often not user-friendly. Our goal is to establish Hong Kong's first computer-assisted patient identification tool for rare diseases, starting with inborn errors of metabolism (IEM). METHODS: Patient data from 2010 to 2019 was retrieved from electronic databases. Through big data analytics, patient data were filtered based on specific IEM-related biochemical and genetic tests. Clinical notes were analyzed using a rule-based natural language processing technique called regular expression. The algorithm classified each extracted paragraph as "IEM-related" or "not IEM-related." Pathologists reviewed the paragraphs for curation, and the algorithm's performance was evaluated. RESULTS: Out of 46,419 patients with IEM-related tests, the algorithm identified 100 as "IEM-related." After pathologists' validation, 96 cases were confirmed as true IEM, with 1 uncertain case and 3 false positives. A secondary ascertainment yielded a sensitivity of 92.3% compared to our previously published IEM cohort. CONCLUSIONS: Our artificial intelligence approach provides a novel method to identify IEM patients, facilitating the creation of a centralized, computer-assisted rare disease patient registry at the local and national levels. This data can potentially be accessed by multiple stakeholders for collaborative research and to enhance healthcare management for rare diseases.

Suppressing Cis/Trans 'Ring-Flipping' in Organoaluminium(III)-2-Pyridyl Dimers-Design Strategies Towards Lewis Acid Catalysts for Alkene Oligomerisation.

Owing to its high natural abundance compared to the commonly used transition (precious) metals, as well as its high Lewis acidity and ability to change oxidation state, aluminium has recently been explored as the basis for a range of single-site catalysts. This paper aims to establish the ground rules for the development of a new type of cationic alkene oligomerisation catalyst containing two Al(III) ions, with the potential to act co-operatively in stereoselective assembly. Five new dimers of the type [R2Al(2-py')]2 (R=Me, iBu; py'=substituted pyridyl group) with different substituents on the Al atoms and pyridyl rings have been synthesised. The formation of the undesired cis isomers can be suppressed by the presence of substituents on the 6-position of the pyridyl ring due to steric congestion, with DFT calculations showing that the selection of the trans isomer is thermodynamically controlled. Calculations show that demethylation of the dimers [Me2Al(2-py')]2 with Ph3C+ to the cations [{MeAl(2-py')}2(µ-Me)]+ is highly favourable and that the desired trans disposition of the 2-pyridyl ring units is influenced by steric effects. Preliminary experimental studies confirm that demethylation of [Me2Al(6-MeO-2-py)]2 can be achieved using [Ph3C][B(C6F5)4].

Mast cell activation and nutritional disorders in patients with hypermobility.

PURPOSE OF REVIEW: Individuals with joint hypermobility disorders are increasingly referred to gastroenterology services for support with the investigation and management of gastrointestinal complaints. Individuals can present with a myriad of complex coexisting diagnoses, the inter-relationship of which is unclear. This review discusses the proposed association between hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorder (HSD) with disorders of mast cell activation and provides an overview of gastrointestinal symptoms and nutritional outcomes in this patient cohort. RECENT FINDINGS: It is unclear whether a true association between hEDS/HSD and mast cell activation disorders exists. There is a high prevalence of nonspecific gastrointestinal symptoms in individuals with hEDS/HSD and patients may be at risk of macro-nutrient and micro-nutrient deficiencies, although the current evidence base is limited. SUMMARY: We advocate a pragmatic approach to the investigation and management of gastrointestinal symptoms in patients with hEDS/HSD. This centres on excluding organic pathology, discussing the overlap with disorders of gut-brain interactions, trialling evidence-based therapies targeting individual symptoms, and supporting nutritional deficiencies where present via the least invasive approach. Engagement with a broad multidisciplinary team is also important to support the holistic needs of this patient cohort.

Performance of Artificial Intelligence in Detecting Diabetic Macular Edema From Fundus Photography and Optical Coherence Tomography Images: A Systematic Review and Meta-analysis.

BACKGROUND: Diabetic macular edema (DME) is the leading cause of vision loss in people with diabetes. Application of artificial intelligence (AI) in interpreting fundus photography (FP) and optical coherence tomography (OCT) images allows prompt detection and intervention. PURPOSE: To evaluate the performance of AI in detecting DME from FP or OCT images and identify potential factors affecting model performances. DATA SOURCES: We searched seven electronic libraries up to 12 February 2023. STUDY SELECTION: We included studies using AI to detect DME from FP or OCT images. DATA EXTRACTION: We extracted study characteristics and performance parameters. DATA SYNTHESIS: Fifty-three studies were included in the meta-analysis. FP-based algorithms of 25 studies yielded pooled area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity of 0.964, 92.6%, and 91.1%, respectively. OCT-based algorithms of 28 studies yielded pooled AUROC, sensitivity, and specificity of 0.985, 95.9%, and 97.9%, respectively. Potential factors improving model performance included deep learning techniques, larger size, and more diversity in training data sets. Models demonstrated better performance when validated internally than externally, and those trained with multiple data sets showed better results upon external validation. LIMITATIONS: Analyses were limited by unstandardized algorithm outcomes and insufficient data in patient demographics, OCT volumetric scans, and external validation. CONCLUSIONS: This meta-analysis demonstrates satisfactory performance of AI in detecting DME from FP or OCT images. External validation is warranted for future studies to evaluate model generalizability. Further investigations may estimate optimal sample size, effect of class balance, patient demographics, and additional benefits of OCT volumetric scans.

CYP2U1: An emerging treatable neurometabolic disease with cerebral folate deficiency in 2 Chinese brothers.

With the rapid advancement of medical technologies in genomic and molecular medicine, the number of treatable neurometabolic diseases is quickly expanding. Spastic paraplegia 56 (SPG56), one of the severe autosomal recessive forms of neurodegenerative disorders caused by pathogenic variants in the CYP2U1 gene, has no reported specific targeted treatment yet. Here we report 2 Chinese brothers with CYP2U1 bi-allelic pathogenic variants with cerebral folate deficiency who were treated for over a decade with folinic acid supplement. Patients have remained stable under therapy.

Reaction dynamics as the missing puzzle piece: the origin of selectivity in oxazaborolidinium ion-catalysed reactions.

The selectivity in a group of oxazaborolidinium ion-catalysed reactions between aldehyde and diazo compounds cannot be explained using transition state theory. VRAI-selectivity, developed to predict the outcome of dynamically controlled reactions, can account for both the chemo- and the stereo-selectivity in these reactions, which are controlled by reaction dynamics. Subtle modifications to the substrate or catalyst substituents alter the potential energy surface, leading to changes in predominant reaction pathways and altering the barriers to the major product when reaction dynamics are considered. In addition, this study suggests an explanation for the mysterious inversion of enantioselectivity resulting from the inclusion of an orthoiPrO group in the catalyst.

Allan-Herndon-Dudley syndrome in Hong Kong: Implication for newborn screening.

BACKGROUND: Allan-Herndon-Dudley syndrome (MCT 8 deficiency) is an X-linked recessive condition caused by hemizygous pathogenic variants in SLC16A2 encoding the monocarboxylate transporter 8 (MCT8). Patients present with global developmental delay and neurological impairment, and abnormal serum thyroid function tests. The drug, 3,3',5 triiodothyroacetic acid (TRIAC), was recently demonstrated to improve the endocrinological profile. Improvement in diagnostic approach is key to earlier start of treatment. PATIENT FINDINGS: We described four Chinese patients with MCT8 deficiency undergoing different diagnostic odysseys. Their initial presentation included global developmental delay and dystonia. Patient 2 also had epilepsy. Patients 1 and 2 presented with two novel variants: (1)hemizygous NM_006517.4(SLC16A2):c.1170 + 2 T > A; p.(?), and (2)hemizygous NM_006517.4(SLC16A2):c.305dupT; p.(Val103GlyfsTer17) respectively. Patients 3 and 4 were biological brothers harboring hemizygous NM_006517.4(SLC16A2):c.305dupT; p.(Val103GlyfsTer17), which was first reported in 2004. We obtained the measurement of triiodothyronine (T3) and reverse T3 (rT3) from dried blood spot samples collected on Day 1 of life from Patient 1 and studied the biomarkers (rT3 and T3/rT3 ratio) proposed by Iwayama et al. for the detection of MCT8 deficiency at birth. Our data verified the significantly reduced rT3 level in Patient 1, compared with healthy newborns, although low T3 level and comparable T3/rT3 ratio with controls were detected. SUMMARY: Patients with MCT8 deficiency often undergo diagnostic odysseys. An early diagnosis could be missed by a normal newborn thyroid function screening result based on biochemical measurement of TSH and/or T4/fT4. Early detection of rT3 is key to improving current diagnostic approach. CONCLUSION: We recommend that full thyroid function profile (TSH, T4/fT4, T3/fT3, rT3) be considered early for all pediatric patients presenting with unexplained developmental delay and/or dystonia. The potential inclusion of rT3 measurement in newborn screening may prove promising.

CONFPASS: Fast DFT Re-Optimizations of Structures from Conformation Searches.

CONFPASS (Conformer Prioritizations and Analysis for DFT re-optimizations) has been developed to extract dihedral angle descriptors from conformational searching outputs, perform clustering, and return a priority list for density functional theory (DFT) re-optimizations. Evaluations were conducted with DFT data of the conformers for 150 structurally diverse molecules, most of which are flexible. CONFPASS gives a confidence estimate that the global minimum structure has been found, and based on our dataset, we can have 90% confidence after optimizing half of the FF structures. Re-optimizing conformers in order of the FF energy often generates duplicate results; using CONFPASS, the duplication rate is reduced by a factor of 2 for the first 30% of the re-optimizations, which include the global minimum structure about 80% of the time.

Acupuncture for post-stroke depression: a systematic review and network meta-analysis.

BACKGROUND: Patients with post-stroke depression (PSD) usually experience anxiety, hopelessness, and insomnia, which have a negative impact on their daily activities and post-stroke rehabilitation. Acupuncture (AC), as a minimally invasive technique, has become a popular choice for improving depression symptoms. However, it is still unclear which therapy is associated with the best outcomes for PSD. In this review, we aimed to explore the impact of AC in alleviating symptoms of PSD and to evaluate the difference in effectiveness between AC combined with pharmacotherapies and various non-pharmacotherapies. METHODS: Six databases and three clinical trials registration platforms were searched from inception to March 2023. Randomized clinical trial comparing needle-based AC with pharmacotherapy, and other non-pharmacotherapy or invalid group were included. Two independent reviewers identified eligible studies, and collected data using a pre-made form. A Bayesian network meta-analysis was conducted to assess and compare different techniques using RStudio 3.6.0 with the package 'GEMTC' V.0.8.1. The primary outcome was the efficacy for PSD assessed by scales measuring depressive symptoms. The secondary outcomes were effectiveness for neurological function and the quality of life. The ranking probabilities for all treatment interventions was performed using the Surface Under the Cumulative Ranking curve (SUCRA). The risk of bias was assessed by using the Revised Cochrane Risk of Bias tool 2. RESULTS: Sixty-two studies, involving 5308 participants published from 2003 to 2022, were included. The results showed that compared with western medicine (WM) (defined as pharmacotherapy for PSD), AC alone or with repetitive transcranial magnetic stimulation (RTMS), Traditional Chinese medicine (TCM) alone or with WM, were superior for alleviating depression symptoms. Compared to Usual Care, AC alone or plus other therapies could significantly decrease scores on the Hamilton Depression Rating scale. According to result of SUCRA, AC plus RTMS had the highest probability of improving depressive symptoms with a probability of 49.43%. CONCLUSIONS: The results of this study indicate that AC alone or combined with other therapies appears to be effective in improving depression symptoms of stroke survivors. Moreover, in comparison to WM, AC alone or plus RTMS, TCM, TCM with WM, or WM, were more effective in improving depression symptoms of PSD. Also, AC with RTMS seems to be the most effective with the highest probability. REGISTRATION: This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database in November 2020 and updated in July 2021. The registration number is CRD42020218752.

Selective Functionalisation of 5-Methylcytosine by Organic Photoredox Catalysis.

The epigenetic modification 5-methylcytosine plays a vital role in development, cell specific gene expression and disease states. The selective chemical modification of the 5-methylcytosine methyl group is challenging. Currently, no such chemistry exists. Direct functionalisation of 5-methylcytosine would improve the detection and study of this epigenetic feature. We report a xanthone-photosensitised process that introduces a 4-pyridine modification at a C(sp3 )-H bond in the methyl group of 5-methylcytosine. We propose a reaction mechanism for this type of reaction based on density functional calculations and apply transition state analysis to rationalise differences in observed reaction efficiencies between cyanopyridine derivatives. The reaction is initiated by single electron oxidation of 5-methylcytosine followed by deprotonation to generate the methyl group radical. Cross coupling of the methyl radical with 4-cyanopyridine installs a 4-pyridine label at 5-methylcytosine. We demonstrate use of the pyridination reaction to enrich 5-methylcytosine-containing ribonucleic acid.

Targeting mutant dicer tumorigenesis in pleuropulmonary blastoma via inhibition of RNA polymerase I.

DICER1 mutations predispose to increased risk for various cancers, particularly pleuropulmonary blastoma (PPB), the commonest lung malignancy of childhood. There is a paucity of directly actionable molecular targets as these tumors are driven by loss-of-function mutations of DICER1. Therapeutic development for PPB is further limited by a lack of biologically and physiologically-representative disease models. Given recent evidence of Dicer's role as a haploinsufficient tumor suppressor regulating RNA polymerase I (Pol I), Pol I inhibition could abrogate mutant Dicer-mediated accumulation of stalled polymerases to trigger apoptosis. Hence, we developed a novel subpleural orthotopic PPB patient-derived xenograft (PDX) model that retained both RNase IIIa and IIIb hotspot mutations and recapitulated the cardiorespiratory physiology of intra-thoracic disease, and with it evaluated the tolerability and efficacy of first-in-class Pol I inhibitor CX-5461. In PDX tumors, CX-5461 significantly reduced H3K9 di-methylation and increased nuclear p53 expression, within 24 hours' exposure. Following treatment at the maximum tolerated dosing regimen (12 doses, 30 mg/kg), tumors were smaller and less hemorrhagic than controls, with significantly decreased cellular proliferation, and increased apoptosis. As demonstrated in a novel intrathoracic tumor model of PPB, Pol I inhibition with CX-5461 could be a tolerable and clinically-feasible therapeutic strategy for mutant Dicer tumors, inducing antitumor effects by decreasing H3K9 methylation and enhancing p53-mediated apoptosis.

Mitochondrial diseases in Hong Kong: prevalence, clinical characteristics and genetic landscape.

OBJECTIVE: To determine the prevalence of mitochondrial diseases (MD) in Hong Kong (HK) and to evaluate the clinical characteristics and genetic landscape of MD patients in the region. METHODS: This study retrospectively reviewed the phenotypic and molecular characteristics of MD patients from participating public hospitals in HK between January 1985 to October 2020. Molecularly and/or enzymatically confirmed MD cases of any age were recruited via the Clinical Analysis and Reporting System (CDARS) using relevant keywords and/or International Classification of Disease (ICD) codes under the HK Hospital Authority or through the personal recollection of treating clinicians among the investigators. RESULTS: A total of 119 MD patients were recruited and analyzed in the study. The point prevalence of MD in HK was 1.02 in 100,000 people (95% confidence interval 0.81-1.28 in 100,000). 110 patients had molecularly proven MD and the other nine were diagnosed by OXPHOS enzymology analysis or mitochondrial DNA depletion analysis with unknown molecular basis. Pathogenic variants in the mitochondrial genome (72 patients) were more prevalent than those in the nuclear genome (38 patients) in our cohort. The most commonly involved organ system at disease onset was the neurological system, in which developmental delay, seizures or epilepsy, and stroke-like episodes were the most frequently reported presentations. The mortality rate in our cohort was 37%. CONCLUSION: This study is a territory-wide overview of the clinical and genetic characteristics of MD patients in a Chinese population, providing the first available prevalence rate of MD in Hong Kong. The findings of this study aim to facilitate future in-depth evaluation of MD and lay the foundation to establish a local MD registry.

A prospective follow-up of thyroid volume and thyroiditis features on ultrasonography among survivors of predominantly mild to moderate COVID-19.

Background: We previously showed that higher SARS-CoV-2 viral load correlated with smaller thyroid volumes among COVID-19 survivors at 2 months after acute COVID-19. Our current follow-up study evaluated the evolution of thyroid volumes and thyroiditis features within the same group of patients 6 months later. Methods: Adult COVID-19 survivors who underwent thyroid ultrasonography 2 months after infection (USG1) were recruited for follow-up USG 6 months later (USG2). The primary outcome was the change in thyroid volume. We also reassessed thyroiditis features on USG, thyroid function and anti-thyroid antibodies. Results: Fifty-four patients were recruited (mean age 48.1 years; 63% men). The mean thyroid volume increased from USG1 to USG2 (11.9 ± 4.8 to 14.5 ± 6.2 mL, p < 0.001). Thirty-two patients (59.3%) had significant increase in thyroid volume by ≥15%, and they had a median increase of +33.3% (IQR: +20.0% to +45.0%). Multivariable logistic regression analysis showed that only higher baseline SARS-CoV-2 viral load independently correlated with significant thyroid volume increase on USG2 (p = 0.022). Among the seven patients with thyroiditis features on USG1, six (85.7%) had the features resolved on USG2. None had new thyroiditis features on USG2. All abnormal thyroid function during acute COVID-19 resolved upon USG1 and USG2. Conclusion: Most COVID-19 survivors had an increase in thyroid volume from early convalescent phase to later convalescent phase. This increase correlated with high initial SARS-CoV-2 viral load. Together with the resolution of thyroiditis features, these may suggest a transient direct atrophic effect of SARS-CoV-2 on the thyroid gland with subsequent recovery of thyroid volume and thyroiditis features.

Investigating the Relationship between Home Parenteral Support and Needs-Based Quality of Life in Patients with Chronic Intestinal Failure: A National Multi-Centre Longitudinal Cohort Study.

Home parenteral support (HPS) is an essential but potentially burdensome treatment that can affect quality of life (QoL). The aims of this longitudinal study were to understand whether any changes in HPS over time were associated with QoL. The Parenteral Nutrition Impact Questionnaire (PNIQ) was used, and data were collected on HPS prescribed at three time points. Data were analysed using multi-level mixed regression models presented as effect size and were adjusted for confounders. Study recruited 572 participants from 15 sites. Of these, 201 and 145 completed surveys at second and third time-points, respectively. PNIQ score was out of 20 with a higher score indicating poorer QoL. Any reduction in HPS infusions per week was associated with an improved PNIQ score of -1.10 (95% CI -2.17, -0.02) unadjusted and -1.34 (95% CI -2.45, -0.24) adjusted. Per day change to the number of infusions per week was associated with a change in the PNIQ score of 0.32 (95% CI -0.15, 0.80) unadjusted and 0.34 (95% CI -0.17, 0.85) adjusted. This is the largest national study to demonstrate improvements in QoL associated with HPS reduction over time using an HPS-specific and patient-centric tool, adding unique data for use of therapies in intestinal failure.