Spatially Resolved Quantum Sensing with High-Density Bubble-Printed Nanodiamonds.

Nitrogen-vacancy (NV-) centers in nanodiamonds have emerged as a versatile platform for a wide range of applications, including bioimaging, photonics, and quantum sensing. However, the widespread adoption of nanodiamonds in practical applications has been hindered by the challenges associated with patterning them into high-resolution features with sufficient throughput. In this work, we overcome these limitations by introducing a direct laser-writing bubble printing technique that enables the precise fabrication of two-dimensional nanodiamond patterns. The printed nanodiamonds exhibit a high packing density and strong photoluminescence emission, as well as robust optically detected magnetic resonance (ODMR) signals. We further harness the spatially resolved ODMR of the nanodiamond patterns to demonstrate the mapping of two-dimensional temperature gradients using high frame rate widefield lock-in fluorescence imaging. This capability paves the way for integrating nanodiamond-based quantum sensors into practical devices and systems, opening new possibilities for applications involving high-resolution thermal imaging and biosensing.

Correlations of response rate and progression-free survival with overall survival in immunotherapy trials for metastatic non-small-cell lung cancer: an FDA pooled analysis.

BACKGROUND: Radiographic changes might not fully capture the treatment effects of immune checkpoint inhibitors (ICIs). We aimed to assess correlations of overall response rate and progression-free survival with overall survival in trials of ICIs for metastatic non-small-cell lung cancer (NSCLC). METHODS: To assess trial-level and patient-level correlations of overall response rate and progression-free survival with overall survival, we conducted a pooled analysis of first-line randomised trials (including patients aged ≥18 years with metastatic squamous and non-squamous NSCLC and an Eastern Cooperative Oncology Group performance status of 0-1) submitted to the US Food and Drug Administration from June 24, 2016, to March 16, 2021. Eligible trials evaluated at least one ICI in the experimental group versus chemotherapy in the control group. At the trial level, we used weighted linear regression to derive coefficients of determination (R2). At the patient level, we used Cox proportional hazards models to compare overall survival between responders versus non-responders per Response Evaluation Criteria in Solid Tumours (version 1.1). FINDINGS: A total of 13 trials including 9285 patients evaluated ICIs alone or in combination with chemotherapy versus chemotherapy alone. At the trial level, the R2 was 0·61 (95% CI 0·32-0·84) for correlation of overall response rate with overall survival and 0·70 (0·40-0·89) for correlation of progression-free survival with overall survival. Correlations ranged from weak to moderate when evaluating subgroups by PD-L1 expression and were consistent across trials evaluating ICIs alone or in combination with chemotherapy. At the patient level, responders had longer overall survival than non-responders (hazard ratio [HR] 0·28 [95% CI 0·26-0·30]). Among responders, overall survival was longer in patients enrolled in experimental groups than in control groups (HR 0·54 [95% CI 0·48-0·61]). INTERPRETATION: Correlations of overall response rate and progression-free survival with overall survival were generally moderate in this pooled analysis. The findings support routine analysis of mature overall survival data, where feasible, in first-line randomised trials of ICIs for metastatic NSCLC. FUNDING: US Food and Drug Administration.

Biophysical characterization of chloride intracellular channel 6 (CLIC6).

Chloride intracellular channels (CLICs) are a family of proteins that exist in soluble and transmembrane forms. The newest discovered member of the family CLIC6 is implicated in breast, ovarian, lung gastric, and pancreatic cancers and is also known to interact with dopamine-(D(2)-like) receptors. The soluble structure of the channel has been resolved, but the exact physiological role of CLIC6, biophysical characterization, and the membrane structure remain unknown. Here, we aimed to characterize the biophysical properties of this channel using a patch-clamp approach. To determine the biophysical properties of CLIC6, we expressed CLIC6 in HEK-293 cells. On ectopic expression, CLIC6 localizes to the plasma membrane of HEK-293 cells. We established the biophysical properties of CLIC6 by using electrophysiological approaches. Using various anions and potassium (K+) solutions, we determined that CLIC6 is more permeable to chloride-(Cl-) as compared to bromide-(Br-), fluoride-(F-), and K+ ions. In the whole-cell configuration, the CLIC6 currents were inhibited after the addition of 10 µM of IAA-94 (CLIC-specific blocker). CLIC6 was also found to be regulated by pH and redox potential. We demonstrate that the histidine residue at 648 (H648) in the C terminus and cysteine residue in the N terminus (C487) are directly involved in the pH-induced conformational change and redox regulation of CLIC6, respectively. Using qRT-PCR, we identified that CLIC6 is most abundant in the lung and brain, and we recorded the CLIC6 current in mouse lung epithelial cells. Overall, we have determined the biophysical properties of CLIC6 and established it as a Cl- channel.

The impact of cancer metastases on COVID-19 outcomes: A COVID-19 and Cancer Consortium registry-based retrospective cohort study.

BACKGROUND: COVID-19 can have a particularly detrimental effect on patients with cancer, but no studies to date have examined if the presence, or site, of metastatic cancer is related to COVID-19 outcomes. METHODS: Using the COVID-19 and Cancer Consortium (CCC19) registry, the authors identified 10,065 patients with COVID-19 and cancer (2325 with and 7740 without metastasis at the time of COVID-19 diagnosis). The primary ordinal outcome was COVID-19 severity: not hospitalized, hospitalized but did not receive supplemental O2, hospitalized and received supplemental O2, admitted to an intensive care unit, received mechanical ventilation, or died from any cause. The authors used ordinal logistic regression models to compare COVID-19 severity by presence and specific site of metastatic cancer. They used logistic regression models to assess 30-day all-cause mortality. RESULTS: Compared to patients without metastasis, patients with metastases have increased hospitalization rates (59% vs. 49%) and higher 30 day mortality (18% vs. 9%). Patients with metastasis to bone, lung, liver, lymph nodes, and brain have significantly higher COVID-19 severity (adjusted odds ratios [ORs], 1.38, 1.59, 1.38, 1.00, and 2.21) compared to patients without metastases at those sites. Patients with metastasis to the lung have significantly higher odds of 30-day mortality (adjusted OR, 1.53; 95% confidence interval, 1.17-2.00) when adjusting for COVID-19 severity. CONCLUSIONS: Patients with metastatic cancer, especially with metastasis to the brain, are more likely to have severe outcomes after COVID-19 whereas patients with metastasis to the lung, compared to patients with cancer metastasis to other sites, have the highest 30-day mortality after COVID-19.

Impact of Increasing PD-L1 Levels on Outcomes to PD-1/PD-L1 Inhibition in Patients With NSCLC: A Pooled Analysis of 11 Prospective Clinical Trials.

BACKGROUND: Programmed death ligand 1 (PD-L1) expression is recognized as a key biomarker in the treatment of non-small cell lung cancer (NSCLC) with anti-PD(L)1 inhibitors. Previous work has highlighted that outcomes in patients with NSCLC treated with anti-PD(L)1 inhibitors generally improve with increasing PD-L1 expression. The objectives of these analyses are to quantitate the effect of PD-L1 expression on outcomes, to characterize the potentially nonlinear relationship between PD-L1 expression and outcomes, and to assess potential differences in these relationships across subgroups. PATIENTS AND METHODS: We performed a retrospective, pooled analysis of 11 clinical trials submitted to the US FDA between 2015 and 2022 that included patients with advanced NSCLC treated with anti-programmed death 1 or anti-PD-L1 immune checkpoint inhibitor (ICI) monotherapy in the first-line (1L) or second-line (2L) treatment setting. The clinical outcomes explored were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). RESULTS: The primary analysis population included 3806 patients with advanced NSCLC, of which 2040 were treated in 1L and 1766 in 2L. For patients with a PD-L1 score of 100% in the 1L setting, the hazard ratio versus a patient with 1% PD-L1 was 0.55 (95% CI, 0.43 to 0.70) for OS and 0.50 (95% CI, 0.41 to 0.61) for PFS. For patients with a PD-L1 score of 100% in the 2L setting, the hazard ratio versus a patient with 0% PD-L1 was 0.55 (95% CI, 0.43 to 0.71) for OS and 0.51 (95% CI, 0.41 to 0.63) for PFS. Subgroup analyses suggested that this relationship may vary by subgroup, particularly by region. CONCLUSIONS: These analyses suggest PD-L1 expression has an appreciable impact on clinical outcomes for patients with NSCLC treated with ICI. As the impact of PD-L1 expression on outcomes may vary across regions, it is critical that future trials are multiregional and enroll a diverse patient population.

FDA approval summary: fam-trastuzumab deruxtecan-nxki for unresectable or metastatic non-small cell lung cancer with activating HER2 mutations.

On August 11, 2022, FDA granted accelerated approval to fam-trastuzumab deruxtecan-nxki (DS-8201a, T-DXd, ENHERTU, Daiichi Sankyo) for adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating human epidermal growth factor receptor 2 (HER2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy. The approval was based on a prespecified interim analysis of DESTINY-Lung02 (Study U206), a multi-center, randomized, dose-optimization trial in patients with NSCLC harboring activating HER2-mutations. At the approved dose of 5.4 mg/kg given intravenously every 3 weeks, the overall response rate (ORR) was 58% (95% confidence interval [CI]: 43, 71). The median duration of response was 8.7 months (95% CI: 7.1, not estimable). These results were consistent with response rates observed at the 6.4 mg/kg dose level. The most common (≥ 20%) adverse reactions were nausea, constipation, decreased appetite, vomiting, fatigue, and alopecia. The rate of interstitial lung disease (ILD) or pneumonitis was 6% at the 5.4 mg/kg dose level and 14% at the 6.4 mg/kg dose level. In the setting of similar efficacy and reduced toxicity, approval was granted for the 5.4 mg/kg dose level. The applicant conducted a randomized, dose-optimization study with guidance from the FDA Oncology Center of Excellence's Project Optimus. This is the first approval of a targeted therapy for HER2-mutated NSCLC.

Calls to action on lung cancer management and research.

Lung cancer, the leading cause of cancer-related deaths globally, remains a pressing health issue despite significant medical advances. The New York Lung Cancer Foundation brought together experts from academia, the pharmaceutical and biotech industries as well as organizational leaders and patient advocates, to thoroughly examine the current state of lung cancer diagnosis, treatment, and research. The goal was to identify areas where our understanding is incomplete and to develop collaborative public health and scientific strategies to generate better patient outcomes, as highlighted in our "Calls to Action." The consortium prioritized 8 different calls to action. These include (1) develop strategies to cure more patients with early-stage lung cancer, (2) investigate carcinogenesis leading to lung cancers in patients without a history of smoking, (3) harness precision medicine for disease interception and prevention, (4) implement solutions to deliver prevention measures and effective therapies to individuals in under-resourced countries, (5) facilitate collaborations with industry to collect and share data and samples, (6) create and maintain open access to big data repositories, (7) develop new immunotherapeutic agents for lung cancer treatment and prevention, and (8) invest in research in both the academic and community settings. These calls to action provide guidance to representatives from academia, the pharmaceutical and biotech industries, organizational and regulatory leaders, and patient advocates to guide ongoing and planned initiatives.

Characterizing the Conformational Dynamics of Human SUMO2: Insights into its Interaction with Metal Ions and SIMs.

SUMO (Small Ubiquitin-like Modifiers) proteins are involved in a crucial post-translational modification commonly termed as SUMOylation. In this work, we have investigated the native-state conformational flexibility of human SUMO2 and its interaction with Cu2+ and Zn2+ ions using 15N-1H based 2D NMR spectroscopy. After SUMO1, SUMO2 is the most studied SUMO isoform in humans which shares 45 % and ~80 % similarity with SUMO1 in terms of sequence and structure, respectively. In this manuscript, we demonstrate that compared to SUMO1, several amino acids around the α1-helix region of SUMO2 access energetically similar near-native conformations. These conformations could play a crucial role in SUMO2's non-covalent interactions with SUMO interaction motifs (SIMs) on other proteins. The C-terminal of SUMO2 was found to bind strongly with Cu2+ ions resulting in a trimeric structure as observed by gel electrophoresis. This interaction seems to interfere in its non-covalent interaction with a V/I-x-V/I-V/I based SIM in Daxx protein.

Incidentally detected diaphragmatic eventration as para-cardiac thoracic activity on myocardial perfusion imaging.

Diaphragmatic eventration is the elevation of hemi-diaphragm without any disruption to diaphragmatic continuity which can be congenital or acquired. The most common acquired cause is phrenic nerve paralysis due to traumatic causes and is usually incidentally diagnosed on chest radiograph or computed tomography. We hereby report a case of a patient who had road traffic accident with fracture of the left proximal femur. Stress Myocardial Perfusion Imaging (MPI) done for pre-operative clearance showed an incidental tracer avidity adjoining to left myocardium in the thorax. It was confirmed on anatomical imaging to be gastric cavity uptake due to diaphragm eventration.

Potential application of 68Ga-FAPI PET/CT for diagnosing cardiac sarcoidosis.

Detecting cardiac sarcoidosis; a potentially life-threatening condition is challenging and requires a multimodality imaging approach using echocardiography, PET/CT and CMR. Although 18F-FDG is the recommended PET tracer for evaluating cardiac sarcoidosis, it is limited by physiological cardiac FDG uptake and requires stringent patient preparation/ dietary modifications before imaging. We hereby present a case of cardiac sarcoidosis demonstrating myocardial FAPI uptake on cardiac PET, highlighting the potential role of 68Ga-FAPI PET in the evaluation of cardiac sarcoidosis.

Er 3 + , Nd 3 + , Tm 3 + : Up-conversion in Lead Borophosphate Glasses for Visible Emission.

To investigate the role of PbO as a former or a modifier and effect of its compositional variation on the physical, structural and optical properties, lithium lead borophosphate glasses were synthesized by melt quenching technique. For the physical properties of the prepared glasses, density was measured using the Archimedes principle, which showed an increasing trend from 3.13 to 4.51 with increasing concentrations of lead oxide. Additionally, other physical parameters were calculated based on the measured density values. The structural analysis were performed through X-ray diffraction and Fourier transform infrared spectroscopy. Lack of sharp and characteristic peaks in the XRD spectra confirmed the non crystalline nature of the prepared glasses. Structural units due to PbO, P 2 O 5 and B 2 O 3 were identified from the FTIR spectra. Ultraviolet-visible absorption spectroscopy was performed for optical properties and increase in the indirect band gap from 4.80 eV to 4.90 eV was observed. One glass sample was chosen for doping of erbium, neodymium, thulium and ytterbium, for study of their up-conversion properties. The UV-Vis-NIR absorption spectra of erbium, neodymium, and thulium samples were recorded, and wavelength of 980 nm was chosen for excitation. Ytterbium, acting as a sensitizer, facilitated the conversion of the excitation infrared light into visible light. Upon excitation at 980 nm, the erbium-doped sample emitted light at 520 nm, 547 nm, and 665 nm, utilizing excited state up-conversion (ESA) and energy transfer up-conversion (ETU) mechanisms. Similarly, the neodymium-doped sample emitted at 542 nm, 602 nm, and 660 nm, while the thulium-doped sample emitted at 488 nm, 521 nm, and 649 nm. The results of up-conversion indicate that rare earth-doped lithium lead borophosphate glasses are excellent hosts for up-conversion processes.

Artificial intelligence in colorectal multidisciplinary team meetings. What are the medicolegal implications?

AIM: To give an insight into areas for future development and suggestions in the complexities of incorporation of AI into human colorectal cancer (CRC) care while bringing into focus the importance of clinicians' roles in patient care. METHODS: Existing literature around AI use in CRC care is reviewed and potential regulatory issues and medicolegal implications around its implementation in CRC multidisciplinary team meetings (MDTs) are identified. RESULTS: Challenges with patient privacy and confidentiality, patient consent, inequity and bias, patient autonomy, as well as AI system transparency and the liability and accountability issues arising from complications that arise from AI-aided clinical decisions are important focusses associated with the use of AI in CRC MDTs. CONCLUSION: Consideration of various medicolegal aspects of the use of AI in CRC MDTs is warranted to ensure its safe and smooth incorporation into CRC MDTs. AI function as a clinical decision support system and does not replace professional expertise.

Charge-symmetric and -asymmetric fragmentation dynamics of argon dimers in slow Ar8+-Ar2 collisions.

We present an experimental study of multiple-electron capture-induced fragmentation dynamics of Ar2m+ (4 ≤m≤ 7) dimer ions in 4 keV/u Ar8+-Ar2 collisions. The fragment recoil ion pairs and the charge-changing projectiles are coincidentally measured using a double coincidence technique. The branching ratios between the different charge-sharing fragmentation channels show an inherent enhancement of the asymmetric channels. The kinetic energy release (KER) distributions for the associated electron capture process show a shift in the mean KER values toward the higher side with increasing capture stabilization. The interplay between the different projectile autoionization processes sheds light on the energy depositions to the system during collisions. The Coulomb potential energy curves give a physical insight into the role of the projectile final states in the dimer fragmentation dynamics. The dimer-axis orientation-dependent cross sections for the asymmetric fragmentation channels reveal a forward-backward asymmetry that arises from the geometry of the collision system. Our findings thus give insight into the impact parameter-controlled fragmentation dynamics of multiply charged Ar2m+ dimer ions in highly charged ion-dimer slow collisions.

Mortality from pulmonary hypertension in Europe 2001-2019.

BACKGROUND: The incidence of Pulmonary Hypertension (PH) and Pulmonary Arterial Hypertension (PAH) is believed to be on the rise and is associated with poor outcomes. METHODS: We extracted age-standardized mortality rates (ASMRs) for decedents ≥ 18 years of age from the World Health Organization Mortality Database, using International Classification of Diseases 10th edition codes for PH and PAH, covering the period from 2001 to 2019. The UK and European Union countries with at least 1,000,000 inhabitants and at least 75% of available data points over the study period were included. RESULTS: Between 2001 and 2019, in countries with available data, the median ASMR for PH increased by + 1.19 per 1,000,000 (+ 22.51%) in females and + 0.36 per 1,000,000 (+ 6.06%) in males. Out of 19 countries, 13 demonstrate an increase in female PH ASMR, and 12 reported an increase in male PH ASMR. In contrast, median PAH ASMR decreased by -0.29 per 1,000,000 (-28.74%) in females and remained relatively unchanged in males, with a minor increase of + 0.01 per 1,000,000 (+ 1.07%). Notably, there was significant inter-country heterogeneity, with countries such as Hungary, Romania, and Poland displaying results incongruous with the rest of Europe. CONCLUSIONS: While publicly available mortality statistics for PH may be unreliable, these data suggest an overall increase in mortality across Europe from 2001 to 2019. However, mortality from PAH has shown a decrease in females and a modest increase in males. This underscores the urgent need for robust and high-quality mortality reporting, including international registries, for both PH and PAH.

Ultrasound-guided corticosteroid injection in the coracohumeral ligament in patients with Adhesive Capsulitis of the shoulder: A double-blinded, sham-controlled randomized study.

BACKGROUND: Contracture and thickening of the coracohumeral ligament (CHL) occur in patients with adhesive capsulitis. This adversely affects the movement and function of the shoulder joint. There is limited evidence that explores the effectiveness of an isolated steroid injection into CHL in combination with physical therapy. This prospective randomized control trial aimed to evaluate the clinical effects of ultrasound-guided corticosteroid injection compared to a sham injection into the CHL in subjects with adhesive capsulitis. METHODS: Forty patients (23 males, 52.2 ± 8 years of age) with unilateral adhesive capsulitis (with 5.4 ± 2 months mean duration of symptoms) were randomly assigned to either the experimental or control group. Both groups received ultrasound-guided injections into the CHL. The experimental group (n=20) received corticosteroids and the control group (n=20) received a sham lidocaine injection. All subjects underwent supervised conventional physical therapy three times a week for 3 months. Subjects were evaluated for improvements in pain, range of motion, and disability at 6 and 12 weeks as compared to pre-injection baseline measurements. Data were compared statistically across groups and times at p<0.05. The CHL thickness was compared at baseline across sides using paired t-tests. RESULTS: The experimental group showed statistically greater improvements in pain, functional scores, flexion, abduction, internal and external rotation range of motion at 12 weeks compared to the control group. Pain reduction was observed in both groups at 6 and 12 weeks, but the experimental group exhibited significantly greater reductions. The CHL was significantly thicker on the affected side as compared to the unaffected side (p<0.001). DISCUSSION AND CONCLUSION: This study partially supported the hypothesis. Notably, significant improvements in pain, range of motion, and functional scores were observed at 12 weeks in the experimental group. The greater improvements in pain and external rotation may have resulted in lower disability scores in the experimental group. The results emphasize the importance of targeted intervention into the CHL.

Complex Three-Dimensional Microscale Structures for Quantum Sensing Applications.

We present a novel method for fabricating highly customizable three-dimensional structures hosting quantum sensors based on nitrogen vacancy (NV) centers using two-photon polymerization. This approach overcomes challenges associated with structuring traditional single-crystal quantum sensing platforms and enables the creation of complex, fully three-dimensional, sensor assemblies with submicroscale resolutions (down to 400 nm) and large fields of view (>1 mm). By embedding NV center-containing nanoparticles in exemplary structures, we demonstrate high sensitivity optical sensing of temperature and magnetic fields at the microscale. Our work showcases the potential for integrating quantum sensors with advanced manufacturing techniques, facilitating the incorporation of sensors into existing microfluidic and electronic platforms, and opening new avenues for widespread utilization of quantum sensors in various applications.

Mitochondrial Oxidative Stress Regulates FOXP3+ T-Cell Activity and CD4-Mediated Inflammation in Older Adults with Frailty.

In healthy older adults, the immune system generally preserves its response and contributes to a long, healthy lifespan. However, rapid deterioration in immune regulation can lead to chronic inflammation, termed inflammaging, which accelerates pathological aging and diminishes the quality of life in older adults with frailty. A significant limitation in current aging research is the predominant focus on comparisons between young and older populations, often overlooking the differences between healthy older adults and those experiencing pathological aging. Our study elucidates the intricate immunological dynamics of the CD4/Treg axis in frail older adults compared to comparable age-matched healthy older adults. By utilizing publicly available RNA sequencing and single-cell RNA sequencing (scRNAseq) data from peripheral blood mononuclear cells (PBMCs), we identified a specific Treg cell subset and transcriptional landscape contributing to the dysregulation of CD4+ T-cell responses. We explored the molecular mechanisms underpinning Treg dysfunction, revealing that Tregs from frail older adults exhibit reduced mitochondrial protein levels, impairing mitochondrial oxidative phosphorylation. This impairment is driven by the TNF/NF-kappa B pathway, leading to cumulative inflammation. Further, we gained a deeper understanding of the CD4/Treg axis by predicting the effects of gene perturbations on cellular signaling networks. Collectively, these findings highlight the age-related relationship between mitochondrial dysfunction in the CD4/Treg axis and its role in accelerating aging and frailty in older adults. Targeting Treg dysfunction offers a critical basis for developing tailored therapeutic strategies aimed at improving the quality of life in older adults.

Evaluation of the Efficacy and Safety of Intravenous Immunoglobulin (IVIG) in Moderate-to-Severe Hospitalized COVID-19 Patients: A Randomized, Open-Label Parallel-Group Study.

Purpose: Since February 2020, the world has been overwhelmed by the SARS-CoV-2 outbreak, and several patients suffered interstitial pneumonia and respiratory failure requiring mechanical ventilation, threatening the capability of healthcare systems to handle this amount of critical cases. Intravenous immunoglobulins (IVIG) possess potential immunomodulatory properties beneficial for COVID-19 patients, yet evidence supporting IVIG as adjunctive therapy remains sparse. This study evaluated the outcomes of adjunctive IVIG with the standard of care (SoC) in moderate-to-severe COVID-19 patients. Methods: This randomized study included 59 moderate-to-severe COVID-19 patients with known comorbidities. One arm (n = 33) received high-dose IVIG (400 mg/kg/day) within 48 hours for five days alongside SoC, while the other arm (n = 26) received SoC, comprising steroids, enoxaparin, and remdesivir. The primary endpoint was clinical improvement, as measured by the National Early Warning Score 2 (NEWS2) and discharged/death proportions. Secondary outcomes included IVIG safety, hospitalization duration, changes in oxygen saturation, inflammatory markers, IgG titer, CTSS (CT severity score), and radiological findings. Results: There was an improvement in the NEWS2 at the end of treatment in the IVIG arm (5.67 vs. 5.96). A significant absolute effect improvement (Day 1 vs. Day 9) was seen in serum LDH, D-dimer, hs-CRP, IL-6, CTSS, procalcitonin, respiratory rate, and chest radiographic findings. SARS-CoV-2 IgG titer increased significantly in the IVIG arm. There was a statistically significant reduction in mortality in the IVIG group (5 vs. 10). Conclusion: IVIG was a safe and effective adjunctive therapy to SoC treatment in moderate-to-severe COVID-19 patients needing ventilatory support. Furthermore, studies are required to validate our findings. This trial is registered with CTRI/2021/05/033622.

Community-based study to describe the epidemiology of dengue infection in a large cantonment during one transmission season.

Background: Dengue is one of the most important vector-borne disease in India. It has been linked to monsoons when Aedes aegypti mosquitoes breed profusely in containers. No study exists in Armed Forces wherein a community-based sero-survey has described the epidemiology of dengue. The present study tries to fill this knowledge gap. Methods: A total of 422 participants were studied for one transmission season of July-December. Blood samples were collected for testing dengue IgG and IgM at the beginning and at end of the study period. The study participants were interviewed at least twice within this period of 6 months to assess clinical condition and follow-up. Point prevalence and incidence were measured. Distribution of presence or absence of symptoms was noted for positive as well as negative cases. Results: All participants were males. Average age was 31.75 years. Point prevalence at the beginning of transmission season was 11.6% (95% CI: 8.4%-14.6%) and 15.6% (95% CI: 12.1%-19.1%) towards the end. Incidence was found to be 147.4 per 1000 for 6 months. Forty percent of incident cases were asymptomatic. Conclusion: Healthcare planners and hospital commanders in stations across Armed Forces can use the prevalence and incidence figures obtained in this study as a general guide while planning for prevention and control of dengue. Also, this study points to the fact that dengue transmission in Delhi may have shifted earlier to months of April/May than the conventionally accepted season of July-December.

ISCCM Position Statement: Management of Severe Dengue in Intensive Care Unit.

Dengue is one of the commonest causes of undifferentiated acute febrile illness in India as well as South East Asia. Nearly two-fifths of the world population is at risk of infection, and nearly 96 million infections reported worldwide, it is a major cause of concern across the globe. The ISCCM leadership felt that there have been no new directives/guidelines except the MOH guidelines for the management of dengue fever since 2014. Under the auspices of the Indian Society of Critical Care Medicine (ISCCM), an expert group of 14 intensivists from across the country, was formed. The task force members formulated questions that needed to be answered. These questions were validated by the members of ISCCM attending research conclave 2023. All the members systematically searched PubMed, MEDLINE, and Science Direct for original articles on different aspects of dengue management between January 1, 2000, and July 1, 2023. From the collected articles, duplicates were removed. Based on the evidence collected, the expert group members prepared statements/answers to the questions. Since most of the evidence is of moderate to low quality, a consensus was generated amongst the members of the task force. Each statement was agreed upon by 70% of the task force. The statements presented in the article are consensus statements as answers to queries raised. How to cite this article: Bhalla A, Singh H, Suri V, Yaddanapudi L, Poddar B, Ghawat R, et al. ISCCM Position Statement: Management of Severe Dengue in Intensive Care Unit. Indian J Crit Care Med 2024;28(S2):S42-S58.