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Spontaneous intracranial hypotension is uncommon and results from a cerebrospinal fluid (CSF) leak. We describe the case of a marathon runner who presented with postural headache attributable to CSF venous fistulation originating from a lower thoracic nerve root cyst. Subsequent investigations confirmed a unifying de novo diagnosis of human leukocyte antigen B27-associated syndrome. With unmitigated CSF loss over the following 3 months, the patient became bedbound and developed rapidly progressive behavioural variant frontotemporal dementia. Behavioural changes were somewhat reversible on restoration of CSF volume after surgical intervention. [ABSTRACT FROM AUTHOR]

Vitamin D status may indeed be a prognosticator for morbidity and mortality in patients with COVID-19 We read with interest the systemic review and meta-analysis by Munchi et al.1 of emerging evidence that vitamin D deficiency is associated with poorer outcomes and prognosis in patients with COVID-19 and would like to report our experience in the United Kingdom (UK). Although our study was underpowered to detect a mortality difference between deficient and replete groups, our data support that vitamin D status may be a surrogate prognosticator for morbidity and mortality in patients with COVID-19. [Extracted from the article]

Sarcoidosis is an inflammatory disease characterised by non-caseating granulomas of unclear aetiology. Isolated cardiac sarcoidosis (ICS) is rare and occurs when there is granulomatous infiltration of myocardial tissue without evidence of extracardiac sarcoidosis. The heterogeneity in clinical manifestations often presents a diagnostic challenge which leads to delays in treatment initiation. Our case highlights the often quiescent presentation of ICS, the importance of early treatment and the diagnostic challenges that contribute to its underdiagnosis. [ABSTRACT FROM AUTHOR]

Pericardial cysts are uncommon benign lesions of the middle mediastinum, making up less than 6% of all mediastinal masses. They are often detected as incidental findings on chest imaging and some can resolve spontaneously. Rarely, however, they may cause symptoms of chest pain, right ventricular outflow obstruction, and persistent cough. Furthermore, they may affect cardiac tamponade after acute rupture or cyst haemorrhage resulting in sudden death. We report the case of a 102-year-old woman presenting with urosepsis, in whom routine chest radiography was initially suspicious of advanced bronchial carcinoma. Further imaging supported a diagnosis of one of the largest pericardial cysts described in the literature located in the right parahilar space. The patient was appropriately managed conservatively. [ABSTRACT FROM AUTHOR]

Haemolysis is a rare but serious complication of cytomegalovirus (CMV) infection, described mostly in immunocompromised patients, the pathogenesis of which is yet to be fully elucidated. We describe a case of Coombs-positive haemolytic anaemia in an older Caucasian immunocompetent woman after polytrauma, resulting from suspected reactivation of CMV infection and secondary cold agglutinin disease. Clinicians should consider CMV infection in the differential diagnosis of haemolytic anaemia in immunocompetent older adults who are admitted with significant musculoskeletal trauma. Early treatment with B-cell depletion therapy to halt cold agglutinin production can be life-saving. [ABSTRACT FROM AUTHOR]

Background and Objectives: Nutritional anemia is a significant public health issue with 50-80% prevalence in Indian children. Fortification of food, specifically milk, with iron is a potential approach to increase dietary iron intake. Ferric pyrophosphate [Fe4(P2O7)3] is organoleptically neutral and is less soluble in acid medium and, further, has low bioavailability in milk. However, since ascorbic acid is a potent enhancer of iron absorption, the coadministration of ascorbic acid with Fe4(P2O7)3 might enhance the absorption of iron. We evaluated the effect of ascorbic acid on iron absorption from a Fe4(P2O7)3 and an ascorbic acid fortified milk beverage with respect to milk fortified with Fe4(P2O7)3 alone.Methods and Study Design: A double-blind, two-way crossover, randomized study was conducted in 25 mildly anemic children. The test group received milk fortified with beverage powder containing 7 mg isotopically labeled iron (57Fe/58Fe) as Fe4(P2O7)3, equimolar proportions of ascorbic acid and 200 mg of calcium whereas control group received milk fortified with energy, calcium and iron equivalent beverage powder. Fractional iron absorption was measured by erythrocyte incorporation of stable isotopes of iron (57Fe/58Fe) in both the groups.Results: The fractional iron absorption from the control drink was 0.80% (95% CI: 0.57, 1.12). Fortifying the milk with an equimolar amount of ascorbic acid increased the fractional iron absorption almost 2-fold to 1.58% (95% CI: 1.13, 2.22).Conclusions: The presence of ascorbic acid in an equimolar ratio with that of iron from Fe4(P2O7)3 salt in milk as a fortificant enhanced iron absorption when compared to milk fortified with only Fe4(P2O7)3. [ABSTRACT FROM AUTHOR]

Development of drug delivery systems, not the drug discovery, has become more cynosures towards the efficacy of drug against the target cells. Modified hybrid cationic vesicles (HCV) were formulated using soylecithin (SLC), ion pair amphiphile (IPA, hexadecyltrimethylammonium-dodecylsulfate, HTMA + -DS - ), bi-tail cationic surfactant dialkyldimethylammonium bromides (DXDABs, bis-C 12 to C 18 ) and cholesterol. Piroxicam (Px), a conventional non steroidal anti inflamatory drug (NSAID), with potent yet unexplored anticancer activity,was encapsulated in the hybrid vesicles. Dual impact of DXDABs and Px on SLC/IPA were scrutinized in the form of monolayer, bilayer and solid supported bilayer. Favourable hydrophobic inteaction between SLC/IPA and dihexadecyldimethylammonium bromide (DHDAB) as well as the intercalation of Px molecules between the amphiphiles were noticed through the surface pressure area measuremnts. Vesicles without and with Px were fairly monodisperse with positive zeta potential (Z. P.) and considerably stable upto two months. Size of the vesicles enhanced with Px incorporation. Vesicles maintain spherical morphology as revealed from the electronic microscopic studies. Differential scanning calaorimetry and FTIR studies confirm the location of Px membrane palisade that enhances the extent of hydration by increasing the proportion of H-bonding. Bilayer thickness and the spacing between two adjecent lamellar phase were investigated by combined small angle neutron scattering and small angle X-ray scattering. Atomic force microscopic studies confirm the Px induced fluidization of membrane bilayer. The entrapment efficiency of vesicles to host Px depends on the amount of IPA present in the bilayer. Px hosted cationic vesicles showed less than 2% hemolysis. The drug reigned supreme over human neuroblastoma cell line (SH-SY 5Y) when encapsulated inside the membrane and was non toxic to normal human blood cell lymphocyte (PBMC) as revealed from cytotoxicity assay. [ABSTRACT FROM AUTHOR]

A water soluble heteroglycan (PS-II) with an average molecular weight ∼ 60 kDa was isolated from the hot aqueous extract of an edible mushroom Lentinus fusipes . The structural characterization of PS-II was carried out using total acid hydrolysis, methylation analyses, periodate oxidation, Smith degradation and 1D/2D NMR experiments. Total acid hydrolysis indicated the presence of D-galactose and D-glucose in a molar ratio of approximately 1:1. The chemical and NMR analyses revealed that the proposed repeating unit of the PS-II had a backbone chain consisting of three (1 → 6)-linked α- d -galactopyranosyl residue and two (1 → 6)-linked β- d -glucopyranosyl residues, one of the β- d -glucopyranosyl residue was branched at O -3 position with a terminal β- d -glucopyranosyl. The PS-II exhibited significant in vitro splenocyte and macrophage activations with optimum dose of 20 μg/ml and 80 μg/ml respectively. Flow cytometry study revealed the protective role of the PS-II against nicotine stimulated lymphocytes. Moreover, the ROS scavenging property of PS-II was also established using DPPH radical scavenging assay. [ABSTRACT FROM AUTHOR]

Introduction Surgical inpatients frequently require peripherally inserted central catheters (PICCs) for parenteral feeding and administration of medication. PICCs may cause upper limb deep venous thrombosis (ULDVT), which impacts patient morbidity. We investigated the risk and prevention of PICC-ULDVT in hospitalised surgical inpatients. Methods We conducted a retrospective analysis of 168 consecutive surgical inpatients who received a PICC over the same four-year period. Data from 136 additional consecutive general medical inpatients with PICCs over the same period were included for comparison. We observed and compared the incidence of ULDVT confirmed on dedicated upper limb venous imaging in the cohort of surgical patients compared to a time matched cohort of medical patients. We extracted data including patient demographics, details of admission, and insertion site of the PICC from the hospital electronic notes. Results The incidence of ULDVT in surgical patients was 4.7% compared to 1.5% in medical patients despite increased age (p=0.001) and comorbidity burden (p=0.001) in the latter group. Ninety percent of surgical patients had abdominal surgery within 30 days of PICC placement. Regression multivariate analysis identified concurrent cancer (p=0.048), median Charlson Comorbidity Index (CCI) (p=0.034), admission with malignant bowel obstruction (p=0.002), and catheter insertion into the brachial vein (p=0.033) as significant risk factors for PICC-ULDVT in hospitalised surgical patients. Standard pharmacological venous thromboembolic events (VTE) prophylaxis, as per national guidelines, did not reduce the risk of PICC-ULDVT. Conclusion Our study indicates that surgical inpatients are at greater risk of developing PICC-associated upper limb deep vein thrombosis (ULDVT) compared to medical inpatients, with limited evidence supporting the effectiveness of pharmacological thromboprophylaxis in reducing this risk. PICCs should be used with caution in patients with cancer, cancer-related bowel obstruction, and surgical patients with a higher comorbidity index. PICCs inserted via the basilic vein may reduce ULDVT risk, but further studies are needed on the preferential site of insertion in surgical patients., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Wexham Park Hospital, Frimley Research, Quality Improvement and Excellence Department issued approval FH581. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Li et al.)

Background: QRS fragmentation (fQRS) is a depolarization disorder that can be detected on routine electrocardiography (ECG). Current evidence suggests that fQRS is a prognosticator of adverse cardiovascular events. This study aimed to assess the relationship between fQRS and all-cause mortality in critically unwell coronavirus disease 2019 (COVID-19) patients and to investigate the significance of associated abnormalities on echocardiography., Methods: A retrospective cohort study of COVID-19 patients in a critical care setting was performed. Electrocardiography was performed on presentation to hospital, admission to the critical care unit, and at subsequent points according to clinical need. Transthoracic echocardiography was performed at clinical discretion to assess for structural and functional cardiac abnormalities. Primary outcome was in-hospital mortality and secondary outcome was the need for mechanical invasive ventilation., Results: Totally, 212 consecutive patients were included of which 120 (57%) exhibited fQRS and inferior leads were involved in 88% of the patients. Overall, fQRS was a significant predictor of mortality [65% vs. 44% P =.003; multivariate odds ratio = 2.96, 95% confidence interval (CI): 1.42-6.40, P =.005] and inferior fQRS itself was a significant predictor of mortality (P =.03). There was no significant association between fQRS and the need for invasive mechanical ventilation. A total of 112 patients underwent echocardiography. There was a greater incidence of right ventricular (RV) dilatation in the fQRS group (16% vs. 2% respectively, P =.02) and pulmonary hypertension (33% vs. 14% respectively, P =.03) based on echocardiographic criteria., Conclusion: Our study demonstrates that fQRS is significantly associated with RV dilation, pulmonary hypertension, and mortality in critically unwell COVID-19 patients.

The bulk of higher order organismal genomes is comprised of transposable element (TE) copies, i.e. genetic parasites. The host-parasite relation is multi-faceted, varying across genomic region (genic versus intergenic), life-cycle stages, tissue-type and of course in health versus pathological state. The reach of functional genomics though, in investigating genotype-to-phenotype relations, has been limited when TEs are involved. The aim of this review is to highlight recent progress made in understanding how TE origin biochemical activity interacts with the central dogma stages of the host genome. Such interaction can also bring about modulation of the immune context and this could have important repercussions in disease state where immunity has a role to play. Thus, the review is to instigate ideas and action points around identifying evolutionary adaptations that the host genome and the genetic parasite have evolved and why they could be relevant., (© The Author(s) 2022. Published by Oxford University Press.)

Right heart thrombus in transit or "free-floating right heart thrombus" is defined as thrombus(i) arising from the deep veins that embolises to the right atrium or right ventricle before reaching the pulmonary vasculature. It is almost always associated with pulmonary thromboembolism and is a medical emergency with reported mortality rates of over 40%. We present two cases of right heart thrombus in transit with pulmonary thromboembolism resulting from venous thrombosis associated with peripherally inserted central catheters that were managed with different approaches. The cases highlight that clinicians should have a low threshold to utilise imaging modalities such as computerised tomography and transthoracic echocardiography when there is an untoward change in physiological parameters among patients with peripherally inserted central catheters, particularly those with risk factors for peripherally inserted central catheter associated venous thrombosis. Furthermore, procedural optimisation surrounding peripherally inserted central catheters, such as insertion technique and choice of lumen size, is underscored., (© 2023. The Author(s).)

Competing Interests: No financial or personal conflicts of interest for any author.

Background: It is increasingly recognised that older patients may not present with typical symptoms of COVID-19., Aims: This study aims to evaluate the incidence, characteristics and clinical outcome of older adults with atypical presentations of COVID-19., Methods: A retrospective analysis of adults ≥ 65 years with confirmed COVID-19 admitted to our institution between 1 March and 24 April 2020 was performed. Patients were categorised into typical or atypical groups based on primary presenting complaint in the community., Results: One hundred twenty-two patients (mean age 81 ± 8 years; 62 male) were included. Seventy-three (60%) were categorised into the typical group and 49 (40%) into the atypical group. In the atypical group, common presenting complaints were fall in 18 (36%), reduced mobility or generalised weakness in 18 (36%) and delirium in 11 (22%). Further assessment by paramedics and on admission found 32 (65%) to have typical features of COVID-19, fever being the most common, and 22 (44%) were hypoxic. This subset had worse outcomes than those in the typical group with a mortality rate of 50% versus 38%, respectively, although this was not statistically significant (P = 0.27). No significant difference in mortality or length of hospital stay between the groups was demonstrated., Conclusion: Older patients with atypical presentation of COVID-19 in the community are equally susceptible to poor outcomes. Early detection may improve outcomes and limit community transmission. Primary care practitioners should be vigilant and consider prompt onward referral.

Acetylcholinesterase inhibitors such as donepezil delay the progression of Alzheimer's dementia by increasing acetylcholine concentrations in the central nervous system. However, it is becoming apparent that cholinesterase inhibition by donepezil is not confined to the brain. This is supported by previous case reports of peripheral cholinergic side effects and adverse cardiac arrhythmias such as Torsades de Pointes which are reversible upon cessation of donepezil. The augmented acetylcholine concentrations and I Kr inhibition in cardiomyocytes caused by donepezil are believed to mediate this effect.

Background: Vitamin B-12 deficiency is widespread in many parts of the world, affecting all age groups and increasing with age. It is primarily due to a low intake of animal source foods or malabsorption. The measurement of bioavailability of vitamin B-12 is etiologically important in deficiency but is limited due to the use of radioactive isotopes like [57Co]- or [14C]-cyanocobalamin., Objectives: The aim of this study was to measure the bioavailability of [13C]-cyanocobalamin in humans and to assess the effect of parenteral replenishment of vitamin B-12 on the bioavailability., Methods: We synthesized a stable isotope-labeled vitamin B-12, [13C]-cyanocobalamin, using Salmonella enterica by providing [13C2]-ethanolamine as a sole carbon source. After purification and mass spectrometry-based characterization, its oral bioavailability was measured in the fasted state with high and low oral doses, before and after parenteral replenishment of vitamin B-12 stores, from the kinetics of its plasma appearance in a 2-compartment model., Results: [13C]-cyanocobalamin was completely decyanated to [13C]-methylcobalamin describing metabolic utilization, and its plasma appearance showed early and late absorption phases. At a low dose of 2.3 µg, the mean bioavailability was 46.2 ± 12.8 (%, mean ± SD, n = 11). At a higher dose of 18.3 µg, the mean bioavailability was 7.6 ± 1.7 (%, mean ± SD, n = 4). Parenteral replenishment of the vitamin B-12 store in deficient individuals prior to the measurement resulted in a 1.9-fold increase in bioavailability., Conclusions: Vitamin B-12 bioavailability is dose dependent and at a low dose that approximates the normal daily requirement (46%). The stable isotope method described here could be used to define the etiology of deficiency and to inform the dietary requirement in different physiologic states as well as the dose required for supplementation and food fortification. This trial was registered at the Clinical Trials Registry of India as CTRI/2018/04/012957., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Purpose: Sacubitril/valsartan has been demonstrated to improve prognosis and outcomes in heart failure with reduced ejection fraction (HFrEF) patients. We sought to compare the improvement in cardiac function between non-ischaemic and ischaemic cardiomyopathy for patients receiving sacubitril/valsartan., Methods: We conducted a single centre prospective cohort survey of patients reviewed in the Heart Function Clinic between February 2017 and January 2018. Functional evaluation and measurement of biochemical and echocardiographic parameters occurred before the initiation of sacubitril/valsartan, and after 3 months of treatment., Results: We identified 52 patients (26 non-ischaemic and 26 ischaemic cardiomyopathy) suitable for treatment with sacubitril/valsartan. Treatment was followed by a significant decrease in a New York Heart Association (NYHA) class in both patients with non-ischaemic (2.3 ± 0.6 vs. 1.6 ± 0.7, P < 0.001) and ischaemic cardiomyopathy (2.3 ± 0.5 vs. 1.5 ± 0.6, P < 0.001), along with an increase in ejection fraction in both patients with non-ischaemic (26.2% ± 6.5% vs. 37.2% ± 13.8%, P < 0.001) and ischaemic cardiomyopathy (28.1% ± 5.7% vs. 31.5% ± 8.4%, P = 0.007). The improvement in ejection fraction was significantly greater in the patients with non-ischaemic cardiomyopathy compared to those with ischaemic cardiomyopathy (10.7% ± 13.0% vs. 3.9% ± 6.0%, P = 0.023)., Conclusion: Our study suggests that treatment with sacubitril/valsartan in patients with non-ischaemic cardiomyopathy is followed by a greater improvement in ejection fraction than in patients with ischaemic cardiomyopathy.

Fahr's disease is a sporadic or familial neurodegenerative disorder characterized by symmetrical calcification of cerebral structures, particularly the basal ganglia, cerebellar dentate nuclei and surrounding white matter, in the absence of metabolic causes of calcification. We report the case of a previously fit, high functioning 58-year-old man who developed catastrophic irreversible neuropsychiatric collapse after sepsis despite appropriate antimicrobial treatment. Cranial computed tomography revealed extensive diffuse calcifications located in unusual areas. Laboratory studies excluded the presence of other pathologic processes leading to secondary intracranial calcification and a multigene panel failed to confirm mutations in the genes currently known to be associated with the disorder, supporting a diagnosis of sporadic Fahr's disease or idiopathic brain calcification. Important diagnostic considerations in the septic patient who develops neurological complications, namely sepsis-associated encephalopathy and antibiotic-associated encephalopathy, are discussed. The patient remains severely handicapped 6 months after the acute event. Patients with clinically silent neurodegenerative/neuropsychiatric conditions, such as Fahr's disease, may present with florid and unpredicted neurological features in the context of systemic illness., (Copyright © 2020 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Background: The thrombogenic potential of Covid-19 is increasingly recognised. We aim to assess the characteristics of COVID-19 patients diagnosed with pulmonary embolism (PE)., Methods: We conducted a single centre, retrospective observational cohort study of COVID-19 patients admitted between 1st March and 30th April 2020 subsequently diagnosed with PE following computed tomography pulmonary angiogram (CTPA). Patient demographics, comorbidities, presenting complaints and inpatient investigations were recorded., Results: We identified 15 COVID-19 patients diagnosed with PE (median age = 58 years [IQR = 23], 87% male). 2 died (13%), both male patients >70 years. Most common symptoms were dyspnoea (N = 10, 67%) and fever (N = 7, 47%). 12 (80%) reported 7 days or more of non-resolving symptoms prior to admission. 7 (47%) required continuous positive airway pressure (CPAP), 2 (13%) of which were subsequently intubated. All patients had significantly raised D-dimer levels, lactate dehydrogenase (LDH), C-reactive protein (CRP), ferritin and prothrombin times. The distribution of PEs correlated with the pattern of consolidation observed on CTPA in 9 (60%) patients; the majority being peripheral or subsegmental (N = 14, 93%) and only 1 central PE. 10 (67%) had an abnormal resting electrocardiogram (ECG), the commonest finding being sinus tachycardia. 6 (40%) who underwent transthoracic echocardiography (TTE) had structurally and functionally normal right hearts., Conclusion: Our study suggests that patients who demonstrate acute deterioration, a protracted course of illness with non-resolving symptoms, worsening dyspnoea, persistent oxygen requirements or significantly raised D-dimer levels should be investigated for PE, particularly in the context of COVID-19 infection. TTE and to a lesser degree the ECG are unreliable predictors of PE within this context., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Pseudo-azotemia is the syndrome of hypercreatininemia and hyperkaliemia without a change in glomerular filtration rate or structure of the kidney. A 57-year-old vulnerable woman with learning difficulties experienced an intraperitoneal bladder rupture in the absence of a pelvic fracture after a fall. It is suspected that the blunt force compression of a distended bladder situated above the bony protection of the pelvis resulted in delayed intraperitoneal bladder rupture. Urinary ascites resulted in pseudo-azotemia because of urinary creatinine reabsorption across the peritoneum. This "apparent" renal failure is fully reversible when diagnosis and treatment are prompt, with normalization of abnormal laboratory-investigation results often within 24 hours., (Copyright © 2020 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Tolosa-Hunt syndrome is a rare disorder characterized by severe peri-orbital headache and ophthalmoplegia resulting from pseudotumour in the cavernous sinus compressing structures within it, namely cranial nerves III, IV, and VI and the superior divisions of cranial nerve V. We report the case of a 47 year old female who presented with painless left unilateral ptosis and complete external ophthalmoplegia. Magnetic Resonance Imaging (MRI) identified an enhancing heterogeneous mass filling the left cavernous sinus, following the course of the oculomotor nerve. After 2 weeks symptoms and signs resolved and there was a parallel resolution of the MRI findings, without the administration of corticosteroids. As far as we are aware this is one of the first reports of Tolosa-Hunt syndrome variant, with painless neurological involvement confined solely to the oculomotor nerve, and with complete resolution without pharmacological intervention., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Ltd. All rights reserved.)