An insight into the dual role of MoS2-based nanocarriers in anticancer drug delivery and therapy.

Over the years, nanomaterials have been exploited as drug delivery systems and therapeutic agents in cancer treatment. Special emphasis has been placed on structure and shape-mediated drug loading and release. Functional materials, including molybdenum disulfide (MoS2), have shown promising results because of their tunable structure and unmatched physicochemical properties. Specifically, easy surface functionalization and high drug adsorption ability make them ideal candidates. Although the large surface area of nanosheets/nanoflakes may result in high drug loading, the encapsulation efficiency is better for MoS2 nanoflower structures. Due to its high targeting abilities, the loading of chemotherapeutic drugs onto MoS2 may minimize nonspecific cellular death and undesired side effects. Furthermore, due to their strong light-absorption ability, MoS2 nanostructures have been widely exploited as photothermal and photodynamic therapeutic agents. The unexplored dimensions of cancer therapy, including chemodynamic (Fenton-like reaction) and piezo-catalytic (ultrasound-mediated reactive oxygen generation), have been recently unlocked, in which the catalytic properties of MoS2 are utilized to generate toxic free radicals to eliminate cancer. Intriguingly, combining these therapeutic modalities often results in high therapeutic efficacy at low doses and minimizes side effects. With a plethora of recent studies, a thorough analysis of current findings is crucial. Therefore, this review discusses the major advances in this field of research. A brief commentary on the limitations/future outlook/ethical issues of the clinical translation of MoS2-mediated cancer treatments is also deliberated. Overall, in our observations, the MoS2-based nanoformulations hold great potential for future cancer therapy applications. STATEMENT OF SIGNIFICANCE: Development of nanomedicines based on MoS2 has opened new avenues in cancer treatment. The MoS2 with different morphologies (nanosheet/nanoflower/QDs) has shown promising results in controlled and targeted drug delivery, leading to minimized side effects and increased therapeutic efficacy. While existing reviews have primarily focused on the optical/thermal properties utilized in photodynamic/photothermal therapy, the outstanding catalytic properties of MoS2 utilized in cancer therapies (chemodynamic/piezo-catalytic) are often overlooked. This review critically highlights and praises/criticizes individual articles reporting the MoS2-based nanoplatforms for cancer therapy applications. Additionally, MoS2-based combined therapies for synergistic effects are discussed. Furthermore, a brief commentary on the future prospects for clinical translations is also deliberated, which is appealing to various research communities engaged in cancer theranostics and biomedical sciences research.

Coupled 3D (J ≥ 0) Time-Dependent Wave Packet Calculation for the F + H2 Reaction on Accurate Ab Initio Multi-State Diabatic Potential Energy Surfaces.

We had calculated adiabatic potential energy surfaces (PESs), nonadiabatic, and spin-orbit (SO) coupling terms among the lowest three electronic states (12A', 22A', and 12A″) of the F + H2 system using the multireference configuration interaction (MRCI) level of theory, and the adiabatic-to-diabatic transformation equations were solved to formulate the diabatic Hamiltonian matrix [J. Chem. Phys. 2020, 153, 174301] for the entire region of the nuclear configuration space. The accuracy of such diabatic PESs is explored by performing scattering calculations to evaluate integral cross sections (ICSs) and rate constants. The nonadiabatic and SO effects are studied by utilizing coupled 3D time-dependent wave packet formalism with zero and nonzero total angular momentum on multiple adiabatic/diabatic surfaces calculation. We depict the convergence profiles of reaction probabilities for the reactive as well as nonreactive processes on various electronic states at different collision energies with respect to total angular momentum including all helicity quantum numbers. Finally, total ICSs are calculated as functions of collision energies for the initial rovibrational state (v = 0, j = 0) of the H2 molecule along with the temperature-dependent rate coefficient, where those quantities are compared with previous theoretical and experimental results.

Medial surface plating of posterior column through the anterior intrapelvic approach in acetabulum fractures with involvement of both columns.

Aims: Posterior column plating through the single anterior approach reduces the morbidity in acetabular fractures that require stabilization of both the columns. The aim of this study is to assess the effectiveness of posterior column plating through the anterior intrapelvic approach (AIP) in the management of acetabular fractures. Methods: We retrospectively reviewed the data from R G Kar Medical College, Kolkata, India, from June 2018 to April 2023. Overall, there were 34 acetabulum fractures involving both columns managed by medial buttress plating of posterior column. The posterior column of the acetabular fracture was fixed through the AIP approach with buttress plate on medial surface of posterior column. Mean follow-up was 25 months (13 to 58). Accuracy of reduction and effectiveness of this technique were measured by assessing the Merle d'Aubigné score and Matta's radiological grading at one year and at latest follow-up. Results: Immediate postoperative radiological Matta's reduction accuracy showed anatomical reduction (0 to 1 mm) in 23 cases (67.6%), satisfactory (2 to 3 mm) in nine (26.4%), and unsatisfactory (> 3 mm) in two (6%). Merle d'Aubigné score at the end of one year was calculated to be excellent in 18 cases (52.9%), good in 11 (32.3%), fair in three (8.8%), and poor in two (5.9%). Matta's radiological grading at the end of one year was calculated to be excellent in 16 cases (47%), good in nine (26.4%), six in fair (17.6%), and three in poor (8.8%). Merle d'Aubigné score at latest follow-up deteriorated by one point in some cases, but the grading remained the same; Matta's radiological grading at latest follow-up also remained unchanged. Conclusion: Stabilization of posterior column through AIP by medial surface plate along the sciatic notch gives good stability to posterior column, and at the same time can avoid morbidity of the additional lateral window.

Sequential output information based predictive control for event-triggered networked control systems.

In a Networked Control System (NCS), event-triggering is often used to reduce the number of network transmission instances and improve network usage. This paper considers transmitting output data rather than the estimated state for such event-triggered schemes. Output transmission facilitates efficient transmission by reducing the size of the packets sent over the network. However, since the state observer utilizes delayed information output transmission deteriorates system performance and requires improved observer-based prediction schemes for closed-loop control. The performance of a new scheme involving the transmission of sequential output information in a single packet to improve the state observer's performance is demonstrated in this paper. A sequential observer is constructed that uses successive output information to better observe the states, and a prediction scheme is used to take care of the delays due to event-triggering, network delays, and dropouts. Further, event-triggering is employed in both the feedback and forward channels. The demonstrated efficacy of this sequential approach in the networked control of an inverted pendulum system and a DC motor system emphasizes its potential as a practical solution for improved control in NCSs, particularly in the face of network constraints and communication challenges.

Optically active two-dimensional MoS2-based nanohybrids for various biosensing applications: A comprehensive review.

Following the discovery of graphene, there has been a surge in exploring other two-dimensional (2D) nanocrystals, including MoS2. Over the past few decades, MoS2-based nanocrystals have shown great potential applications in biosensing, owing to their excellent physico-chemical properties. Unlike graphene, MoS2 shows layer-dependent finite band gaps (∼1.8 eV for a single layer and ∼1.2 for bulk) and relatively strong interaction with the electromagnetic spectrum. The tunability of the size, shape, and intrinsic properties, such as high optical absorption, electron mobility, mechanical strength and large surface area, of MoS2 nanocrystals, make them excellent alternative probe materials for preparing optical, photothermal, and electrical bio/immunosensors. In this review, we will provide insights into the rapid evolutions in bio/immunosensing applications based on MoS2 and its nanohybrids. We emphasized the various synthesis, characterization, and functionalization routes of 2D MoS2 nanosheets/nanoflakes. Finally, we discussed various fabrication techniques and the critical parameters, including the limit of detection (LOD), linear detection range, and sensitivity of the biosensors. In addition, the role of MoS2 in enhancing the performance of biosensors, the limitations associated with current biosensing technologies, future challenges, and clinical implications are addressed. The advantages/disadvantages of each biosensor technique are also summarized. Collectively, we believe that this review will encourage resolute researchers to follow up further with the state-of-the-art MoS2-based biosensing technology.

Chitosan-insulin nano-formulations as critical modulators of inflammatory cytokines and Nrf-2 pathway to accelerate burn wound healing.

Burn injuries are characterized by prolonged inflammatory phases, neurovascular damage, and hypermetabolism, eventually causing improper tissue regeneration. Insulin has gained considerable attention in normal and diabetic wound healing, yet its role in burn wounds remains poorly understood. In this study, insulin-chitosan nano-formulations (ICNP) were synthesized using a simple and robust mechanism and characterized to monitor specific interactions between insulin and chitosan, and the particles measuring approximately 30 nm in size exhibited mild alterations in the amide I, II, and III bonds of the insulin protein along with impressive insulin loading efficiency of 88.725 ± 0.295% under physiological conditions, and significantly improved burn wound healing in vitro (HEKa cells) and in vivo (murine third-degree burn model). The underlying mechanism behind superior wound closure and tissue remodeling was attributed to significant early phase reduction of pro-inflammatory cytokine IL-6 levels in ICNP-treated mice, while anti-inflammatory cytokine IL-10 levels became markedly elevated, resulting in enhanced re-epithelialization and collagen deposition. Furthermore, treatment of ICNP was associated with unregulated expression of Nrf-2, a key regulator of oxidative stress and inflammation, indicating their molecular crosstalk. These findings highlight the potential of ICNP as a promising therapeutic formulation for burn wound healing, promoting wound closure by modulating inflammatory phases, making it a valuable candidate for further clinical development in burn care.

Strong Laser Field-Driven Coupled Electron-Nuclear Dynamics: Quantum vs Classical Description.

We have performed a coupled electron-nuclear dynamics study of H2+ molecular ions under the influence of an intense few-cycle 4.5 fs laser pulse with an intensity of 4 × 1014 W/cm2 and a central wavelength of 750 nm. Both quantum and classical dynamical methods are employed in the exact similar initial conditions with the aim of head-to-head comparison of two methodologies. A competition between ionization and dissociation channel is explained under the framework of quantum and classical dynamics. The origin of the electron localization phenomena is elucidated by observing the molecular and electronic wave packet evolution pattern. By probing with different carrier envelope phase (CEP) values of the ultrashort pulse, the possibility of electron localization on either of the two nuclei is investigated. The effects of initial vibrational states on final dissociation and ionization probabilities for several CEP values are studied in detail. Finally, asymmetries in the dissociation probabilities are calculated and mutually compared for both quantum and classical dynamical methodologies, whereas Franck-Condon averaging over the initial vibrational states is carried out in order to mimic the existing experimental conditions.

Recent advances in the design of intracellular pH sensing nanoprobes based on organic and inorganic materials.

In the biological system, the intracellular pH (pHi) plays an important role in regulating diverse physiological activities, including enzymatic action, ion transport, cell proliferation, metabolism, and programmed cell death. The monitoring of pH inside living cells is also crucial for studying cellular events such as phagocytosis, endocytosis, and receptor-ligand internalization. Furthermore, some organelles, viz., endosomes and lysosomes, have intracompartmental pH, which is critical for maintaining the stability of protein structure and function. The dysfunction and abnormal pH regulation can result in terminal diseases such as cancer, Alzheimer, and so forth. Therefore, the accuracy of intracellular pH measurement is always the top priority and demands cutting-edge research and analysis. Such techniques, such as Raman spectroscopy and fluorescence imaging, preferably use nanotechnology due to their remarkable advantages, such as a non-invasive approach and providing accuracy, repeatability, and reproducibility. In the past decades, there have been numerous attempts to design and construct non-invasive organic and inorganic materials-based nanoprobes for pHi sensing. For Raman-based techniques, metal nanostructures such as Au/Ag/Cu nanoparticles are utilized to enhance the signal intensity. As for the fluorescence-based studies, the organic-based small molecules, such as dyes, show higher sensitivity toward pH. However, they possess several drawbacks, including high photobleaching rate, and autofluorescence background signals. To this end, there are alternative nanomaterials proposed, including semiconductor quantum dots (QDs), carbon QDs, upconversion nanoparticles, and so forth. Moreover, the fluorescence technique allows for ratiometric measurement of pHi, which as a result, offers a reliable calibration curve. This timely review will critically examine the current progression in the existing nanoprobes. In addition, based on our knowledge and available research findings, we provide a brief future outlook that may advance the state-of-the-art methodologies for pHi sensing.

Synthesis of Cu (II) and Zn (II) Complexes of a Quinoline Based Flexible Amide Receptor as Fluorescent Probe for Dihydrogen Phosphate and Hydrogen Sulphate and Their Antibacterial Activity.

A novel 8-hydroxy quinoline-derived amide receptor, in conjunction with its Cu (II) and Zn (II) complexes, has been strategically developed to function as remarkably efficient fluorescent receptors with a distinct capability for anion sensing. The comprehensive characterization of the synthesized compounds were achieved through UV-Vis, IR, NMR, and HRMS spectroscopic techniques. Among the Cu (II) and Zn (II) complexes, the latter exhibits superior selectivity for anions, specifically dihydrogen phosphate and hydrogen sulfate, as their tetrabutylammonium salts in a 9:1 acetonitrile-water (v/v) mixture. The Cu (II) complex demonstrates enhanced anion binding compared to the amide ligand, albeit with reduced selectivity. Furthermore, the affinity was evaluated using the Benesi-Hildebrand plot. The binding constants and Limit of Detection (LOD) for both complexes were precisely quantified. The Job plot illustrates a clear 1:1 binding interaction between the metal complexes and the guest anions. Significantly, both metal-complex receptors display a broad spectrum of antibacterial activity, against both gram-positive and gram-negative bacteria. It is worth highlighting that the Zn (II) complexed receptor outperforms the Cu (II) complexed receptor, as evidenced by its considerably lower Minimum Inhibitory Concentration (MIC) value against both bacterial strains.

Coupled three-dimensional quantum mechanical wave packet study of proton transfer in H2+ + He collisions on accurate ab initio two-state diabatic potential energy surfaces.

We have carried out fully close-coupled three dimensional quantum mechanical wave packet dynamical calculations for the reaction He+H2+→HeH++H on the ground electronic adiabatic potential energy surface and on the lowest two electronic states of newly constructed ab initio calculated diabatic potential energy surfaces for the system [Naskar et al., J. Phys. Chem. A 127, 3832 (2023)]. With the reactant diatom (H2+) in its roto-vibrational ground state (v = 0, j = 0), the calculations have been carried out in hyperspherical coordinates to obtain the reaction attributes. Convergence profiles of the reaction probability with respect to the total angular momentum quantum number at different collision energies are presented for the title reaction. State-to-state as well as initial state selected integral reaction cross sections are calculated from the fully converged reaction probabilities over a range of collision energies. The integral cross section values computed using the two-state diabatic potential energy surfaces are significantly lower than those obtained using the ground electronic state adiabatic potential energy surface and are in much better agreement with the available experimental results than the latter for total energy greater than 1.1 eV. Therefore, it becomes clear that it is important to include the nonadiabatic coupling terms for a quantitative prediction of the dynamical observables.

Open Repair of Posterior Cruciate Ligament Femoral Peel-Off Lesion in Multiligamentous Knee Injuries Results in Good Outcomes.

Purpose: To identify posterior cruciate ligament (PCL) peel-off lesions, to separate these lesions from more common midsubstance tears, and to evaluate patient outcomes after primary open repair. Methods: Patients with acute femoral-side "peel off"-type lesions associated with multiligamentous injuries who underwent PCL repair were identified. Patients with chronic PCL injuries, midsubstance PCL tears, or PCL tibial avulsions were excluded from the study. A total of 11 patients were included in this study. All patients underwent open repair using a suture pullout technique. Results: The mean follow-up period was 18 months. The mean Lysholm score at 12 months was 87. Mean knee range of motion (flexion) achieved at 12 months was 121°. No patient had grade 3 laxity on posterior stress testing at final follow-up. Conclusions: Our study showed good outcomes after primary repair of femoral PCL peel-off lesions. Level of Evidence: Level IV, therapeutic case series.

Reversible blindness with macrophage activation syndrome: an unusual presentation of secondary antiphospholipid syndrome.

Blindness due to retinal vascular thrombosis is a dreadful complication of antiphospholipid syndrome (APS). The latter may be present in isolation (ie, primary) or may occur secondary to other connective tissue diseases like lupus. Here we present an adolescent girl with bilateral painless loss of vision as a result of central retinal vessel thrombosis due to secondary APS. Her condition was further complicated by the presence of autoimmune haemolytic anaemia and the development of macrophage activation syndrome while being evaluated for her blindness. Prompt treatment with glucocorticoids and anticoagulants could halt the devastating disease process.

Efficacy and Tolerability of Tenofovir/Lamivudine/Dolutegravir among Antiretroviral Therapy Naive Human Immunodeficiency Virus Infected Patients of a Tertiary Care Center in Eastern India.

BACKGROUND: Although many drug regimens have been used in the treatment of human immunodeficiency virus (HIV) infection, the National AIDS Control Organization (NACO) of India recommends the use of a fixed-dose combination of tenofovir/lamivudine/dolutegravir (TLD) as a first-line regimen since 2020. In spite of much global data on the use of this combination, experience in the Indian population is still limited. We aim to find out the efficacy and tolerability of this novel regimen, in a tertiary care center of Eastern India. MATERIALS AND METHODS: A descriptive observational study, longitudinal in design performed in the antiretroviral therapy (ART) center of a tertiary care hospital in Kolkata, West Bengal, India. All patients who attended the ART center from April 2021 to October 2022 were enrolled in the study following inclusion and exclusion criteria. A detailed history, clinical examination, necessary biochemical tests, and CD4 count of all patients were done at baseline. Subsequently, they were followed up for 6 months with monthly visits when they were enquired about any adverse effects requiring therapy interruptions. At the end of 6 months, CD4 count and viral load were measured. RESULTS: Out of a total sample of 249 patients, the TLD regimen was efficacious in 99.2% (n = 247) in whom viral load was suppressed to <1,000 copies/mL after 6 months of treatment. The regimen had to be temporarily discontinued in 6% of patients (n = 15). The most common cause of treatment interruption was hepatic dysfunction (3.2%) followed by cutaneous manifestation (2.4%). In 14 out of 15 patients, the regimen could be reintroduced and was safely tolerated afterward. Only one patient had to be shifted to an alternative regimen due to tenofovir-induced nephrotoxicity. Thus TLD was tolerated in 99.6% (n = 248) patients. CONCLUSION: The fixed-dose combination of TLD is a highly efficacious and well-tolerated first-line regimen for ART naïve patients with HIV infection having >95% adherence. How to cite this article: Sengupta D, Ghosh S, Pain S, et al. Efficacy and Tolerability of Tenofovir/Lamivudine/Dolutegravir among Antiretroviral Therapy Naive Human Immunodeficiency Virus Infected Patients of a Tertiary Care Center in Eastern India. J Assoc Physicians India 2023;71(9):72-74.

Dissociative ionization of the H2 molecule under a strong elliptically polarized laser field: carrier-envelope phase and orientation effect.

A coupled electron-nuclear dynamical study is performed to investigate the sub-cycle dissociation and ionization of the H2 molecule in a strong 750 nm 4.5 fs elliptically polarized laser pulse. A quasi-classical method is employed in which additional momentum-dependent potentials are added to the molecular Hamiltonian to account for the non-classical effects. The effect of molecular orientation with respect to the laser polarization plane on the probabilities of different dynamical channels and proton energy spectra has been examined. We demonstrate the 2D-control of proton anisotropy by manipulating the carrier-envelope phase of the pulse. We demonstrate that the quasi-classical method can capture the carrier-envelope phase effects in the dissociative ionization of the H2 molecule. Our results indicate that the classical models provide an efficient approach to study the mechanistic insights of strong-field molecular dynamics.

A review of carotid and vertebral artery dissection.

Cervical artery dissection is a major cause of ischaemic stroke in young adults. The diagnosis can be challenging as some patients may present with seemingly benign symptoms such as a headache, neck pain or dizziness. However, the neurological sequelae of a transient ischaemic attack, vision loss or ischaemic stroke are potentially devastating. All hospital clinicians must be able to recognise this diagnosis and organise timely and appropriate investigations as antithrombotic treatment reduces the risk of stroke recurrence. This article reviews the literature to provide practical information for clinicians to recognise key risk factors and features of history and examination which should raise suspicion of cervical artery dissection. Diagnosis can now be made using the non-invasive, commonly available modalities of computed tomography angiography or magnetic resonance angiography. Timely treatment with antithrombotic agents is recommended to reduce the rate of an ischaemic stroke.

Accurate Calculation of Rate Constant and Isotope Effect for the F + H2 Reaction by the Coupled 3D Time-Dependent Wave Packet Method on the Newly Constructed Ab Initio Ground Potential Energy Surface.

We employ coupled three-dimensional (3D) time dependent wave packet formalism in hyperspherical coordinates for reactive scattering problem on the newly constructed ab initio calculated ground adiabatic potential energy surface for the F + H2/D2 reaction. The convergence profiles for various reactive channels are depicted at low collision energy regimes with respect to the total angular momentum (J) quantum numbers. For two different reactant diatomic molecules (H2 and D2) initially at their respective ground roto-vibrational state (v = 0, j = 0), calculated state-to-state as well as total integral cross sections as a function of collision energy, temperature dependent rate constants, and the kinetic isotope effect for various reactivity profiles of F + H2 and F + D2 reactions are presented along with previous theoretical and experimental results.

A quality improvement project reducing adverse events and improving adherence to guidelines surrounding VRIII usage.

Variable rate intravenous insulin infusions (VRIII) are frequently used in hospitals and incorrect use can lead to electrolyte imbalance, hypoglycaemia and adverse outcomes. The Joint British Diabetes Societies (JDBS) published guidelines in 2014 and recommended the use of a balanced fluid as substrate. There was no published data to demonstrate the superiority of this fluid in reducing adverse events. This quality improvement project aimed to review the existing practice at our Trust in accordance with JDBS guidelines. We predicted introducing this fluid would reduce adverse events and demonstrating this was a prerequisite condition from our Trust Medicines Management Committee to approve its long-term availability. We carried out an audit of our practice in 2015, at which time the JBDS recommended fluid (0.45% sodium chloride/5% dextrose with 0.15% potassium chloride) was not available in our Trust. Our VRIII guideline was re-written with recommendation for use of the balanced fluid, after procurement from pharmacy. Our primary areas for improvement as highlighted from the 2015 audit were correct substrate prescription and rate reduction of hypokalaemia (potassium <3.5 mmol/L) and hypoglycaemia (glucose <4 mmol/L) during VRIII use. Analysis of the pre-intervention (December 2016) and post-intervention (September-November 2017) data showed a significant increase in correct fluid use; 11% pre-intervention to 76% post-intervention (χ2, p<0.0001). The number of hypoglycaemic events per VRIII reduced from 0.73 (±1.78) to 0.28 (±0.84) (p<0.05) peri-intervention. Similarly, the number of hypokalaemic events per VRIII reduced from 0.15 (±0.54) pre-intervention to 0.05 (±0.25) post-intervention. There was also a significant reduction in number of VRIII episodes associated with a hyponatraemia event from 26% at baseline to 12% post-intervention (p<0.01). Some of these marked improvements were not sustained at 1-year post follow-up. We reduced adverse outcomes with a substantial net-cost saving during this period, through implementation of new and accessible guidelines, trust-wide education programmes and posters to raise awareness.

Bacterioboat-A novel tool to increase the half-life period of the orally administered drug.

The short half-life in the GI tract necessitates an excess of drugs causing side effects of oral formulations. Here, we report the development and deployment of Bacterioboat, which consists of surface-encapsulated mesoporous nanoparticles on metabolically active Lactobacillus reuteri as a drug carrier suitable for oral administration. Bacterioboat showed up to 16% drug loading of its dry weight, intestinal anchorage around alveoli regions, sustained release, and stability in physiological conditions up to 24 hours. In vivo studies showed that oral delivery of 5-fluorouracil leads to increased potency, resulting in improved shrinkage of solid tumors, enhanced life expectancy, and reduced side effects. This novel design and development make this system ideal for orally administrable drugs with low solubility or permeability or both and even making them effective at a lower dose.

Setup for photolithography on microscopic flakes of 2D materials by combining simple-geometry mask projection with writing.

An optical arrangement and procedure for photolithography on microscopic flakes of two-dimensional materials with an arbitrary shape/size is described. The technique combines projection of demagnified images of simple geometry macroscopic masks with writing. Only a few masks, such as vertical/horizontal slit and square hole, are sufficient to generate most of the required patterns. The setup allows for initially locating the photoresist coated flake on a substrate by imaging it. Thereafter, the automated precise sample stage motion followed by projection of the demagnified mask image is repeated several times to expose the photoresist in the shape of the required pattern. Appropriate light wavelength regimes for imaging and for exposure are chosen through automated optical filter switching. Programming steps for the process are described. The setup allows for direct lithography in one round on microscopic samples without requiring sample shape/size specific masks or predefined position markers. Making of electrode lines of width down to 3 µm, at desired locations on tiny flakes of MoS2, is demonstrated.

The clinical profile and associated mortality in people with and without diabetes with Coronavirus disease 2019 on admission to acute hospital services.

INTRODUCTION: To assess if in adults with COVID-19, whether those with diabetes and complications (DM+C) present with a more severe clinical profile and if that relates to increased mortality, compared to those with diabetes with no complications (DM-NC) and those without diabetes. METHODS: Service-level data was used from 996 adults with laboratory confirmed COVID-19 who presented to the Queen Elizabeth Hospital Birmingham, UK, from March to June 2020. All individuals were categorized into DM+C, DM-NC, and non-diabetes groups. Physiological and laboratory measurements in the first 5 days after admission were collated and compared among groups. Cox proportional hazards regression models were used to evaluate associations between diabetes status and the risk of mortality. RESULTS: Among the 996 individuals, 104 (10.4%) were DM+C, 295 (29.6%) DM-NC and 597 (59.9%) non-diabetes. There were 309 (31.0%) in-hospital deaths documented, 40 (4.0% of total cohort) were DM+C, 99 (9.9%) DM-NC and 170 (17.0%) non-diabetes. Individuals with DM+C were more likely to present with high anion gap/metabolic acidosis, features of renal impairment, and low albumin/lymphocyte count than those with DM-NC or those without diabetes. There was no significant difference in mortality rates among the groups: compared to individuals without diabetes, the adjusted HRs were 1.39 (95% CI 0.95-2.03, p = 0.093) and 1.18 (95% CI 0.90-1.54, p = 0.226) in DM+C and DM-C, respectively. CONCLUSIONS: Those with COVID-19 and DM+C presented with a more severe clinical and biochemical profile, but this did not associate with increased mortality in this study.