Heated tobacco product (IQOS) induced pulmonary infiltrates.

Background: Heated tobacco products (HTPs) have been marketed as safer alternatives to conventional cigarettes, but emerging evidence suggests potential respiratory risks. We present a case of pulmonary complications associated with IQOS, a popular HTP, contributing to the growing understanding of these risks. Case description: A 40-year-old chronic smoker switched to IQOS, consuming 1.5 packs per day. He presented with incidental chest radiographic abnormalities and peripheral eosinophilia. Computed tomography of chest revealed pulmonary nodules and ground glass opacities. Bronchoscopy indicated mild eosinophilia. After ruling out other causes, a lung biopsy was recommended but declined. Discontinuation of IQOS led to symptom resolution and radiographic improvement. This case adds to a limited literature on HTP-induced lung injury, with a unique presentation and favorable response to cessation. Conclusions: The case highlights potential pulmonary complications and the first describing an organizing pattern of lung injury associated with IQOS use, emphasizing the importance of recognizing and discontinuing HTPs in patients with respiratory symptoms or radiographic abnormalities. Further research is needed to elucidate the mechanisms underlying the harmful effects of HTPs and inform public health policies. This case underscores the importance of monitoring and educating individuals about the potential risks of HTPs to respiratory health, especially in the context of smokers switching to these products.

Empagliflozin and Rapid Kidney Function Decline Incidence in Type 2 Diabetes: An Exploratory Analysis From the EMPA-REG OUTCOME Trial.

Rationale & Objective: Kidney function progressively declines in most patients with type 2 diabetes (T2DM). Many develop progressive chronic kidney disease (CKD), but some experience a more rapid decline, with a greater risk of kidney failure and cardiovascular disease. In EMPA-REG OUTCOME, empagliflozin was associated with slower kidney disease progression. This post hoc analysis evaluated the effect of empagliflozin (pooled doses) on the prevalence of a "rapid decliner" phenotype, defined by an annual estimated glomerular filtration rate (eGFR) decline of >3 mL/min/1.73 m2. Study Design: This was an exploratory analysis of EMPA-REG OUTCOME, a large randomized, double-blind, placebo-controlled trial in adults with T2DM, established cardiovascular disease and an eGFR of ≥30 mL/min/1.73 m2. Setting & Participants: Analysis was undertaken on 6,967 participants (99.2%) in whom serial eGFR data was available. Interventions: Patients were randomized (1:1:1) to empagliflozin 10 mg, 25 mg, or placebo in addition to standard of care. Outcomes: Annual change in eGFR over the maintenance phase of treatment (week 4 to last value on treatment) was calculated using linear regression models. Logistic regression analysis was used to investigate differences in rapid decline between the treatment groups. Results: Over the study period, a rapid decliner phenotype was observed in 188 (9.5%) participants receiving placebo and 134 (3.4%) receiving empagliflozin. After adjusting for other risk factors, this equated to a two-third reduction in odds (OR, 0.32; 95% CI, 0.25-0.40; P < 0.001) among participants receiving empagliflozin versus placebo. A comparable risk reduction was observed using a threshold of eGFR decline of >5 mL/min/1.73 m2/y (empagliflozin vs placebo, 43 [1.1%] vs 44 [2.2%] participants; OR, 0.47; 95% CI, 0.31-0.72; P < 0.001). Limitations: This is a post hoc analysis of a trial undertaken in participants with T2DM and CVD. Generalization of findings to other settings remains to be established. Conclusions: Patients receiving empagliflozin were significantly less likely to experience a rapid decline in eGFR over a median of 2.6 years of exposure to the study drug. Funding: The Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance. Trial Registration: clinicaltrials.gov ID: NCT01131676.

In most people with type 2 diabetes, their kidney function starts to decline over time. However, in some people, this can happen more rapidly, which can increase their risk of kidney or cardiovascular disease. A major study, EMPA-REG OUTCOME, has shown that empagliflozin, which helps to control blood sugar in people with type 2 diabetes, also reduced the risk of cardiovascular disease events and slowed the progression of kidney disease, when compared with people in the study who received placebo. In this new research from the same major study empagliflozin, compared with a placebo, was shown to reduce the risk of people having a rapid decline in their kidney function over the 3 years of the study.

The First Case of a Homozygous CCNO NM 021147.4 Mutation Associated With Primary Ciliary Dyskinesia in Two Indian Siblings.

Primary ciliary dyskinesia (PCD) is a heterogeneous autosomal recessive disease marked by organ lateralization in 50% of patients, chronic sinopulmonary disease, infertility in men, and neonatal respiratory distress. Respiratory control cells contain CCNO in their apical cytoplasm, which is necessary for the development of multiciliate cells, basal body amplification, and migration. Reduced generation of multiple motile cilia, a rare form of PCD, has been linked to CCNO gene abnormalities. Individuals with CCNO mutations have been reported to suffer from severe lower respiratory infections that cause progressive impairment of lung function. For the first time, we describe the CCNO NM 021147.4 (c.258 262dup.p, Gln88argfs*8 Homozygous) gene mutation in an Indian consanguineous family that resulted in severe PCD.

A cross-sectional study from Qatar on the effect of influenza vaccination on the severity of COVID-19.

To assess and compare the severity of corona virus disease 2019 (COVID-19) infection in patients with and without a history of influenza vaccination. In this cross-sectional study descriptive statistics were used to analyze COVID-19-related parameters, including demographics, comorbidities, and severity. Normally distributed data with mean, standard deviation, and 95% confidence interval (CI) were reported, while non-normally distributed data was presented with median and inter-quartile range. Categorical data was summarized using frequencies and percentages. Associations were assessed using Pearson Chi-square, Fisher Exact, t test, or Mann-Whitney U test. Univariate and multivariate logistic regression methods were used to evaluate the relationship between disease severity, clinical outcomes, influenza vaccination status, and other predictors. Significance was considered for p values < 0.05. Statistical analyses were done using SPSS V.27.0 (IBM Corp) and Epi Info (CDC) software. Between March 2020 and December 2020 before the availability of COVID-19 vaccination, 148,215 severe acute respiratory syndrome corona virus 2 positive patients were studied, with 3519 vaccinated against influenza, and 144,696 unvaccinated. After random sampling at 1:2 ratio, the final analysis included 3234 vaccinated and 5640 unvaccinated patients. The majority (95.4%) had mild or asymptomatic COVID-19, while 4.6% had severe or critical cases as defined by World Health Organization severity grading. Multivariate logistic regression analysis revealed that the vaccinated group had significantly less severe (adjusted odds ratio [OR] 0.683; 95% CI 0.513-0.911, P = .009) and critical (adjusted OR 0.345; 95% CI 0.145-0.822, P = .016) COVID-19 and were less likely to require oxygen therapy (adjusted OR 0.696; 95% CI 0.531-0.912, P = .009) after adjusting for confounders like age, gender and comorbidities. No significant differences in Intensive care unit admissions (adjusted OR 0.686; 95% CI 0.425-1.11, P = .122), mechanical ventilation (adjusted OR 0.631; 95% CI 0.308-1.295, P = .209) and mortality (adjusted OR 1.105; 95% CI 0.348-3.503, P = .866) were noted between the 2 groups. Influenza vaccination may significantly reduce the severity of COVID-19 but has no significant effect on intensive care unit admissions, mechanical ventilation and all- cause mortality.

Primary intrapulmonary thymoma a case report.

Primary intrapulmonary thymoma (PIT), defined as the presence of thymoma tissue in the lung without an accompanying mediastinal component, is uncommon and so offers a diagnostic quandary. We describe the case of PIT in an 81-year-old man.

SARS-CoV-2 mouse adaptation selects virulence mutations that cause TNF-driven age-dependent severe disease with human correlates.

The diversity of COVID-19 disease in otherwise healthy people, from seemingly asymptomatic infection to severe life-threatening disease, is not clearly understood. We passaged a naturally occurring near-ancestral SARS-CoV-2 variant, capable of infecting wild-type mice, and identified viral genomic mutations coinciding with the acquisition of severe disease in young adult mice and lethality in aged animals. Transcriptomic analysis of lung tissues from mice with severe disease elucidated a host antiviral response dominated mainly by interferon and IL-6 pathway activation in young mice, while in aged animals, a fatal outcome was dominated by TNF and TGF-ß signaling. Congruent with our pathway analysis, we showed that young TNF-deficient mice had mild disease compared to controls and aged TNF-deficient animals were more likely to survive infection. Emerging clinical correlates of disease are consistent with our preclinical studies, and our model may provide value in defining aberrant host responses that are causative of severe COVID-19.

A Prospective Cohort Study (OUTSTRIP-COVID) on Functional and Spirometry Outcomes in COVID-19 ICU Survivors at 3 Months.

Purpose: COVID-19 pandemic resulted in a significant number of critical care admissions secondary to severe pneumonia and acute respiratory distress syndrome. We evaluated the short-, medium- and long-term outcomes of lung function and quality of life in this prospective cohort study and reported the outcomes at 7 weeks and 3 months from discharge from intensive care unit. Methods: A prospective cohort study of ICU survivors with COVID-19 was conducted from August 2020 to May 2021 to evaluate baseline demographic and clinical variables as well as determine lung function, exercise capacity, and health-related quality of life (HRQOL) using spirometry and 6-minute walk test (6MWT) conducted in accordance with American Thoracic Society standards, and SF-36 (Rand), respectively. SF-36 is a generic 36 question standardized health survey. Descriptive and inferential statistics (alpha = 0.05) were used to analyse the data. Results: At baseline, 100 participants were enrolled in the study of whom 76 followed up at 3 months. Majority of the patients were male (83%), Asians (84%) and less than 60 years of age (91%). HRQOL showed significant improvement in all domains of SF-36, except in emotional wellbeing. Spirometry variables also showed significant improvement in all variables over time with greatest improvement in percentage predicted Forced expiratory volume 1 (79% vs 88% p < 0.001). 6MWT showed significant improvement in variables of walk distance, dyspnea, and fatigue with greatest improvement in change in oxygen saturation (3% vs 1.44% p < 0.001). Intubation status did not impact the changes in SF-36, spirometry or 6MWT variables. Conclusion: Our findings suggest that ICU survivors of COVID-19 have significant improvement in their lung function, exercise capacity and HRQOL within 3 months of ICU discharge regardless of intubation status.

SGLT2 inhibitors for patients with type 2 diabetes and CKD: a narrative review.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors have recently emerged as an effective means to protect kidney function in people with type 2 diabetes and chronic kidney disease (CKD). In this review, we explore the role of SGLT2 inhibition in these individuals. SGLT2 inhibitors specifically act to inhibit sodium and glucose reabsorption in the early proximal tubule of the renal nephron. Although originally developed as glucose-lowering agents through their ability to induce glycosuria, it became apparent in cardiovascular outcome trials that the trajectory of kidney function decline was significantly slowed and the incidence of serious falls in kidney function was reduced in participants receiving an SGLT2 inhibitor. These observations have recently led to specific outcome trials in participants with CKD, including DAPA-CKD, CREDENCE and EMPA-KIDNEY, and real-world studies, like CVD-REAL-3, that have confirmed the observation of kidney benefits in this setting. In response, recent KDIGO Guidelines have recommended the use of SGLT2 inhibitors as first-line therapy in patients with CKD, alongside statins, renin-angiotensin-aldosterone system inhibitors and multifactorial risk factor management as indicated. However, SGLT2 inhibitors remain significantly underutilized in the setting of CKD. Indeed, an inertia paradox exists, with patients with more severe disease less likely to receive an SGLT2 inhibitor. Concerns regarding safety appear unfounded, as acute kidney injury, hyperkalaemia, major acute cardiovascular events and cardiac death in patients with CKD appear to be lower following SGLT2 inhibition. The first-in-class indication of dapagliflozin for CKD may begin a new approach to managing kidney disease in type 2 diabetes.

Utility of RT-PCR versus electronic track and trace system for pre-procedural COVID-19 screening- a retrospective cohort study.

Background and aims: COVID-19 has disrupted the patient workflow in all healthcare settings. Procedures such as bronchoscopy and spirometry require additional pre-procedure screening for SARS-CoV-2. However, there is uncertainty regarding the utility of this universal pre-procedure screening. The State of Qatar has a robust contact tracing system in place in the form of the mobile application 'Ehteraz.' This study assesses the utility of various pre-procedural screening measures in asymptomatic patients and generate recommendations for any potential improvement in the workflow. Methods: This is a cross-sectional study of asymptomatic patients who had SARS-CoV-2 RT-PCR screening performed before bronchoscopy or lung function testing scheduled on an elective basis. Descriptive statistics were used to summarize and determine the sample characteristics. The rate of the positive PCR test result was subsequently calculated. Results: Two patients (0.34%) tested positive for COVID-19 on their pre-procedural screen. Four patients (0.68%) had an inconclusive result. Conclusion: The positivity rate of SARS-CoV-2 RT-PCR is extremely low in asymptomatic individuals screened before bronchoscopy and spirometry. The authors recommend pre-procedural symptom and electronic application-based contact screening instead of universal pre-procedural SARS-CoV-2 RT-PCR for screening asymptomatic individuals.

Development of a novel angiotensin converting enzyme 2 stimulator with broad implications in SARS-CoV2 and type 1 diabetes.

Angiotensin-converting enzyme 2 (ACE2) is protective in cardiovascular disease, lung injury and diabetes yet paradoxically underlies our susceptibility to SARs-CoV2 infection and the fatal heart and lung disease it can induce. Furthermore, diabetic patients have chronic, systemic inflammation and altered ACE2 expression resulting in increased risk of severe COVID-19 and the associated mortality. A drug that could increase ACE2 activity and inhibit cellular uptake of severe acute respiratory syndrome coronavirus 2 (SARs-CoV2), thus decrease infection, would be of high relevance to cardiovascular disease, diabetes and SARs-CoV2 infection. While the need for such a drug lead was highlighted over a decade ago receiving over 600 citations,1 to date, no such drugs are available.2 Here, we report the development of a novel ACE2 stimulator, designated '2A'(international PCT filed), which is a 10 amino acid peptide derived from a snake venom, and demonstrate its in vitro and in vivo efficacy against SARs-CoV2 infection and associated lung inflammation. Peptide 2A also provides remarkable protection against glycaemic dysregulation, weight loss and disease severity in a mouse model of type 1 diabetes. No untoward effects of 2A were observed in these pre-clinical models suggesting its strong clinical translation potential.

Pyridoxamine prevents increased atherosclerosis by intermittent methylglyoxal spikes in the aortic arches of ApoE-/- mice.

Methylglyoxal (MGO) is a reactive glucose metabolite linked to diabetic cardiovascular disease (CVD). MGO levels surge during intermittent hyperglycemia. We hypothesize that these MGO spikes contribute to atherosclerosis, and that pyridoxamine as a MGO quencher prevents this injury. To study this, we intravenously injected normoglycemic 8-week old male C57Bl6 ApoE-/- mice with normal saline (NS, n = 10) or 25 µg MGO for 10 consecutive weeks (MGOiv, n = 11) with or without 1 g/L pyridoxamine (MGOiv+PD, n = 11) in the drinking water. We measured circulating immune cells by flow cytometry. We quantified aortic arch lesion area in aortic roots after Sudan-black staining. We quantified the expression of inflammatory genes in the aorta by qPCR. Intermittent MGO spikes weekly increased atherosclerotic burden in the arch 1.8-fold (NS: 0.9 ± 0.1 vs 1.6 ± 0.2 %), and this was prevented by pyridoxamine (0.8 ± 0.1 %). MGOiv spikes increased circulating neutrophils and monocytes (2-fold relative to NS) and the expression of ICAM (3-fold), RAGE (5-fold), S100A9 (2-fold) and MCP1 (2-fold). All these changes were attenuated by pyridoxamine. This study suggests that MGO spikes damages the vasculature independently of plasma glucose levels. Pyridoxamine and potentially other approaches to reduce MGO may prevent excess cardiovascular risk in diabetes.

Pulmonary embolism in COVID-19, risk factors and association with inflammatory biomarkers.

The coronavirus disease 2019 (COVID-19) pandemic affected millions of people worldwide resulting in a substantial number of hospitalizations. Venous thromboembolism including pulmonary embolism is a known complication of COVID-19 pneumonia although its incidence in such patients is unclear. In this multicenter retrospective cohort study, we looked at the incidence of pulmonary embolism in COVID-19 patients and its associations with various risk factors including demographics, comorbidities, inflammatory markers and coagulation profiles. We analyzed data from 193 patients of mixed ethnicity with a mean age of 51, mostly South Asians (62%) and Arabs (29%). Diabetes and hypertension were the most prevalent comorbidities accounting for 46% (N = 88) and 36% (N = 71) respectively. Critical COVID-19 illness was diagnosed in 67% of patients. The frequency of COVID-19 related pulmonary embolism was 21.8% (N = 42). We found no association of pulmonary embolism with demographic, comorbid or inflammatory variables. Only a raised D-Dimer was found to be associated with pulmonary embolism. Having a pulmonary embolism had no impact on the length of stay, critical illness, or mortality. Receiving steroids or being on standard thromboprophylaxis or weight/D-Dimer adjusted thromboprophylaxis also had no impact on the frequency of pulmonary embolism. Nine incidents of major bleeding were recorded independent of therapeutic anticoagulation. Patients admitted to the hospital for COVID-19 pneumonia had a relatively high incidence of pulmonary embolism. D-dimer was the only associated laboratory parameter associated with pulmonary embolism. However, further research is needed to evaluate its predictive and prognostic utility, particularly in an older population.