Absence Of Traditional Risk Factors Research Articles

Exercise-Dependent Modulation of Immunological Response Pathways in Endurance Athletes With and Without Atrial Fibrillation.

Atrial fibrillation (AF) is a common arrhythmia characterized by uncoordinated atrial electrical activity. Lone AF occurs in the absence of traditional risk factors and is frequently observed in male endurance athletes, who face a 2- to 5-fold higher risk of AF compared with healthy, moderately active males. Our understanding of how endurance exercise contributes to the pathophysiology of lone AF remains limited. This study aimed to characterize the circulating protein fluctuations during high-intensity exercise as well as explore potential biomarkers of exercise-associated AF. A prospective cohort of 12 male endurance cyclists between the ages of 40 and 65 years, 6 of whom had a history of exercise-associated AF, were recruited to participate using a convenience sampling method. The circulating proteome was subsequently analyzed using multiplex immunoassays and aptamer-based proteomics before, during, and after an acute high-intensity endurance exercise bout to assess temporality and identify potential markers of AF. The endurance exercise bout resulted in significant alterations to proteins involved in immune modulation (eg, growth/differentiation factor 15), skeletal muscle metabolism (eg, α-actinin-2), cell death (eg, histones), and inflammation (eg, interleukin-6). Subjects with AF differed from those without, displaying modulation of proteins previously known to have associations with incident AF (eg, C-reactive protein, insulin-like growth factor-1, and angiopoietin-2), and also with proteins having no previous association (eg, tapasin-related protein and α2-Heremans-Schmid glycoprotein). These findings provide insights into the proteomic response to acute intense exercise, provide mechanistic insights into the pathophysiology behind AF in athletes, and identify targets for future study and validation.

Haemophilus influenzae endocarditis: a case report and literature review.

Haemophilus influenzae (HI) is an exceedingly rare cause of infective endocarditis (IE). We present a case of a 90-year-old female diagnosed with HI-IE involving the native tricuspid valve in the absence of traditional risk factors for right-sided endocarditis. She was treated with a 5-week course of IV Ampicillin from negative cultures and suffered no complications. We also conducted a thorough literature review through PubMed and Google Scholar, which yielded a mere 15 reported cases of HI-IE. Fourteen of the reported HI-IE cases included epidemiological data, showing no gender predominance. The mean age of the subjects was 39.5, with the mitral valve being the most implicated (64%) and tricuspid valve involvement being rare (21%). Native tricuspid valve IE is an uncommon entity, especially in the absence of IV drug use. Haemophilus influenzae is an extremely rare cause of IE, with a literature review showing merely 15 reported cases. This article cites the 16th case of HI-IE published in the literature.

Computed tomographic angiography measures of coronary plaque in clinical trials: opportunities and considerations to accelerate drug translation.

Atherosclerotic coronary artery disease (CAD) is the causal pathological process driving most major adverse cardiovascular events (MACE) worldwide. The complex development of atherosclerosis manifests as intimal plaque which occurs in the presence or absence of traditional risk factors. There are numerous effective medications for modifying CAD but new pharmacologic therapies require increasingly large and expensive cardiovascular outcome trials to assess their potential impact on MACE and to obtain regulatory approval. For many disease areas, nearly a half of drugs are approved by the U.S. Food & Drug Administration based on beneficial effects on surrogate endpoints. For cardiovascular disease, only low-density lipoprotein cholesterol and blood pressure are approved as surrogates for cardiovascular disease. Valid surrogates of CAD are urgently needed to facilitate robust evaluation of novel, beneficial treatments and inspire investment. Fortunately, advances in non-invasive imaging offer new opportunity for accelerating CAD drug development. Coronary computed tomography angiography (CCTA) is the most advanced candidate, with the ability to measure accurately and reproducibly characterize the underlying causal disease itself. Indeed, favourable changes in plaque burden have been shown to be associated with improved outcomes, and CCTA may have a unique role as an effective surrogate endpoint for therapies that are designed to improve CAD outcomes. CCTA also has the potential to de-risk clinical endpoint-based trials both financially and by enrichment of participants at higher likelihood of MACE. Furthermore, total non-calcified, and high-risk plaque volume, and their change over time, provide a causally linked measure of coronary artery disease which is inextricably linked to MACE, and represents a robust surrogate imaging biomarker with potential to be endorsed by regulatory authorities. Global consensus on specific imaging endpoints and protocols for optimal clinical trial design is essential as we work towards a rigorous, sustainable and staged pathway for new CAD therapies.

Severe Acute Respiratory Distress Syndrome with Pneumocystis Jirovecii Pneumonia in Man-To-Man Sexual Relations: A Case Report

Severe Acute Respiratory Distress Syndrome (ARDS) with Pneumocystis jirovecii pneumonia (PJP) is a rare and life-threatening condition predominantly observed in immunocompromised individuals, particularly those with human immunodeficiency virus (HIV) infection. Here, we present a case report of a 22-year-old previously healthy male who developed severe ARDS with PJP with an active background of man-to-man sexual relations. This case report highlights the occurrence of severe ARDS with PJP that can happen to individuals engaged in man-to-man sexual relations. The transmission of PJP through sexual contact in the absence of traditional risk factors presents a unique diagnostic and management challenge. Healthcare providers should be vigilant in considering PJP as a potential cause of severe respiratory distress in patients with a history of high-risk sexual behaviours, regardless of their immune status. Further research is needed to better understand the transmission dynamics and risk factors associated with PJP, especially in sexually active man-to-man individuals. Increased awareness of atypical presentations of PJP is essential to ensuring early diagnosis and appropriate management in such cases.

Rectal perforation secondary to invasive cervical cancer presenting as perineal necrotizing fasciitis with subsequent hindquarter amputation: a case report

Necrotizing fasciitis (NF) is a life-threatening soft tissue infection rarely associated with gynecological malignancies. We present a unique case of NF arising from a locally advanced cervical cancer eroding into the rectum, causing occult fecal spillage leading to severe infection and necessitating a hindquarter amputation. A 39-year-old woman presented with sepsis and a necrotic gluteal wound. Extensive debridement revealed "dishwater"-like discharge throughout the left leg fascial compartments, necessitating hindquarter amputation. Despite initial suspicion of a primary skin infection, further investigation revealed a posterolateral rectal perforation secondary to advanced cervical cancer, confirmed by biopsy and imaging. Microbiology identified Streptococcus constellatus, intermedius, and anginosus. This case highlights the atypical presentation of NF associated with advanced cervical cancer. High clinical suspicion and early surgical intervention are crucial for survival. This case expands the understanding of NF etiology and emphasizes the importance of considering rare causes, even in the absence of traditional risk factors.

When Retinal Vasculitis Wears a Mask: Unveiling Retinal Vasculitis Presented as Branch Retinal Vein Occlusion in a Young Male Patient

Introduction : Retinal vasculitis can present with a range of clinical features. Correct diagnosis and prompt treatment are essential to prevent permanent visual loss. We describe a case of retinal vasculitis with branch retinal vein occlusion (BRVO) as initial diagnosis, which is a rare manifestation in a young individual without any vascular risk factors.
 Case Illustration : A 24-year-old male was referred to our center with a sudden onset of blurry vision of his left eye. He was previously diagnosed with BRVO. The patient denied having any chronic diseases, fever, or sore throat. Visual acuity was 6/18 on the left eye and 6/6 on the right eye, respectively. The anterior segment showed no abnormalities. However, fundus examination revealed prominent retinal sheathing, retinal whitening at the inferior quadrant, and macular star. Systemic diseases, such as Bechet disease, sarcoidosis, and systemic lupus erythematosus were excluded by ancillary tests. One month after the initial examination, the patient reported worsening of vision. Funduscopic examination revealed preretinal hemorrhages and macular star. The patient then received intravitreal injection of anti-vascular endothelial growth factor (VEGF), which helped to resolve the hemorrhage and improve vision.
 Discussion : Further investigations, such as fundus fluorescein angiogram, may aid in the diagnosis and management of this condition. Anti-VEGF therapy may be a useful treatment option for retinal vasculitis-associated hemorrhages.
 Conclusion : Our case highlights the importance of considering retinal vasculitis as a differential diagnosis in young patients presenting with BRVO, even in the absence of traditional risk factors.

Lipoprotein (a) as a cause of premature coronary artery disease; a case report of a 34-year-old male patient presenting with ST elevation myocardial infarction.

Background
 Premature coronary artery disease (PCAD) is considered when coronary artery disease (CAD) occurs in the younger population, less than 45 years old in males. Modifiable risk factors are present in about 80% of patients with PCAD such as smoking, diabetes, high blood pressure and obesity. High serum lipoprotein (a) level has recently emerged as a risk factor for PCAD. However, it is not routinely investigated in young patients presenting with acute coronary syndromes.
 Case Presentation
 A 34-year-old African man presented to our hospital with 2 hours of worsening left sided chest pain. He gave a history of long-standing chest pain in the past that was being managed as peptic ulcer disease. He also complained of a slow heart rate. He had no traditional cardiovascular risk factors. The only significant history was a recent recovery from COVID-19 infection two months prior. His physical examination was only significant for a bradycardia, ECG revealed a hyper acute inferior STEMI without right ventricular involvement. Echo showed a normal left ventricle with reduced ejection fraction (EF: 50%), wall motion abnormalities consistent of an inferior MI. He immediately received streptokinase with good clinical and ECG response. His coronary angiogram showed a severe lesion and plaque rupture in the mid-distal segment of a dominant right coronary artery. Percutaneous coronary intervention (PCI) was successfully done, and one drug eluting stent was implanted. He was placed on guideline directed medical therapy for secondary prevention. The only significant possible aetiology found was an elevated Lipoprotein (a) (137mg/dl). Subsequent serum Lipoprotein (a) remained persistently elevated despite therapy with high dose niacin. He was recommended for a PCSK9 receptor blocker, but this medication is not available in the country and the patient could not meet the costs. He remains stable to current medications with no recurrence of chest pain, two years after the index event, the Lipoprotein (a) levels are still high.
 Conclusions:
 Lipoprotein (a) appears to be an important overlooked cardiovascular risk factor for premature coronary artery disease especially in the absence of traditional risk factors. It should always be considered in the screening of premature coronary cardiovascular disease. The acute presentation in this patient was probably triggered by SARS COV-2 infection.

Association of obesity with cardiovascular disease in the absence of traditional risk factors.

The association between obesity and cardiovascular disease (CVD) in people without traditional CVD risk factors is unclear. This study aimed to investigate the association of obesity with CVD and its subtypes in people without traditional CVD risk factors. Based on the Kailuan cohort study, the included participants were divided into different groups according to levels of body mass index (BMI) and waist height ratio (WHtR), respectively. Multivariate Cox proportional hazard models were used to evaluate the associations. This study included 31,955 participants [men 63.99%; mean age (48.14 ± 3.33) years]. During a median follow-up period of 12.97 (interquartile range: 12.68-13.17) years, 1298 cases of CVD were observed. Compared with the normal BMI group, the hazard ratios (HRs) for CVD, stroke, and myocardial infarction (MI) in the BMI obese group were 1.31 (95% confidence interval [CI] 1.11-1.55), 1.21 (95%CI 1.01-1.46), 1.62 (95%CI 1.13-2.33), respectively. Compared with the WHtR non-obese group, the HRs for CVD, stroke, and MI in the obese group were 1.25(95%CI 1.11-1.41), 1.18 (95%CI 1.03-1.34), 1.57 (95%CI 1.18-2.09), respectively. There was an interaction between age and WHtR (P for interaction was 0.043). The association between WHtR and CVD was stronger in people under 60 years old, with a HR of 1.44 (95%CI 1.24-1.67). We found that obesity increased the risk of CVD in people without traditional CVD risk factors. The association of WHtR with CVD was stronger in people under 60 years old.

Triglyceride-glucose index as a predictor of obstructive sleep apnoea severity in the absence of traditional risk factors.

We evaluated the association between the triglyceride-glucose (TG) index, a marker of insulin resistance, and obstructive sleep apnoea (OSA) severity in patients without diabetes mellitus, obesity, and metabolic syndrome. This retrospective cohort study included 1,527 patients. We used univariate and multivariate analyses to identify the independent predictors associated with OSA. Most patients were males (81.5%) with a mean age of 43.9 ± 11.1 (15-90) years. Based on the apnoea-hypopnea index (AHI), 353 (23.1%) patients were included in the control group, whereas 32.4%, 23.5%, and 21% had mild, moderate, and severe OSA, respectively. The TG index values demonstrated significant associations with OSA patients compared with the control group (p = 0.001). In addition, the mean values of the oxygen desaturation index (ODI), AHI, minimum oxygen saturation, and total sleep time percentage with saturation below 90% demonstrated statistically significant differences among the TG index groups (p: 0.001; p:0.001; p:0.001; p:0.003). The optimal TG index cutoff value to predict OSA was 8.615 (AUC = 0.638, 95% CI = 0.606-0.671, p = 0.001). In multivariate logistic regression analysis, after adjusting for age, sex, and body mass index, the TG index was independently associated with OSA patients. The TG index is independently associated with increased risk for OSA. This indicates that this index, a marker for disease severity, can be used to identify severe OSA patients on waiting lists for PSG.

Prevalence and risk factors for subclinical atherosclerosis amongst adults living with HIV in University of Abuja Teaching Hospital, Gwagwalada.

Subclinical atherosclerosis characterizes cardiovascular diseases (CVD), and Human Immunodeficiency Virus (HIV) infection and antiretroviral therapy (ART) are identified risk factors for atherosclerosis. Meanwhile, data on HIV and atherosclerosis in Nigeria are limited. We sought to estimate the prevalence of subclinical atherosclerosis and associated risk factors amongst adult persons living with HIV/AIDS (PLHIV) enrolled at University of Abuja Teaching Hospital, Gwagwalada, Abuja (UATH). This was a cross-sectional study of 277 consecutively selected PLHIV ≥18 years enrolled for HIV care and treatment at UATH. Pretested structured questionnaire was used to collect data from consenting ART-experienced and ART-naïve patients on risk factors of atherosclerosis. Carotid intima media thickness (CIMT) ≥0.71 mm as measured by Doppler ultrasonography was used to identify patients with sub-clinical atherosclerosis. Two logistic regression models with (Model-A) and without (Model-B) traditional risk factors were fitted to identify risk factors of subclinical atherosclerosis. Participants' mean age was 39.44 ± 10.71 years with female preponderance (64.26%). Overall prevalence of subclinical atherosclerosis was 43.32% (62.25% in ART-experienced). Model-A identified male sex [AOR 4.33(1.74-10.76), p = 0.002], advancing age [30-39 years AOR 5.95(1.31-26.96), p = 0.021]; ≥40 years AOR 19.51(4.30-88.56), p ≤ 0.001), advancing HIV infection [≥WHO stage II AOR 4.19(1.11-15.92), p = 0.035], hypercholesterolemia [AOR 3.88(1.47-10.25), p ≤ 0.001] and ≥5 year duration on ART [AOR 9.05(3.16-25.92), p ≤ 0.001] as risk factors of subclinical atherosclerosis. In Model-B (excluding traditional risk factors) on the other hand, advancing HIV infection [≥WHO stage II AOR 3.93(1.19-13.042), p = 0.025] and duration on ART [≥5 years AOR 11.43(4.62-28.29), p = 0.001] were found as risk factors of subclinical atherosclerosis. Subclinical atherosclerosis was higher in ART-experienced patients, and this was irrespective of presence or absence of traditional risk factors. And advancing HIV disease and duration on ART were found as significant risk factors for subclinical atherosclerosis. We therefore recommend routine CVD risk screening in PLHIV.

Acute limb ischemia in COVID-19 patients despite therapeutic anticoagulation: Experience from Africa

BackgroundHypercoagulability is a common complication seen in COVID-19 infection. However, arterial thrombosis such as acute limb ischemia (ALI) is far less common. Data on the incidence and nature of arterial thromboembolic complications in patients with COVID-19 is limited, originating from a few case reports and case series. Data in the African continent are very scarce. MethodThis is a case series of 10 patients with COVID-19 who developed ALI while on treatment at Eka Kotebe General Hospital, Addis Ababa, Ethiopia. All patients with ALI and COVID-19 admitted between February 1, 2021, and December 31, 2021, were retrospectively identified and reviewed. COVID-19 was confirmed by RT-PCR and ALI was confirmed by Doppler ultrasound and/or computed tomography angiography in the presence of clinical suspicion. ResultsA total of 3098 patients were hospitalized with confirmed COVID-19 during the study period. In a series of 10 patients, 8 (80%) males with a median age of 53.5 years were included. All except one (10%) had one or more risk factors for ALI and one had a ‘possible’ case of vaccine-induced thrombotic thrombocytopenia (VITT) associated with ALI. All were admitted with severe COVID-19 and most (80%) developed ALI during hospitalization (median of seven days from admission). The median duration between COVID-19 and ALI symptom onset was 14.5 days (IQR, 11–15). The majority (60%) were taking therapeutic anticoagulation at the time of ALI onset which is the standard of care for patients with severe disease. Five (50%) were successfully revascularized (median time of 3.5 days) and the rest underwent amputation. All survived and were discharged improved. ConclusionALI can occur in the context of COVID-19 even while a patient is on therapeutic dose anticoagulation and in the absence of traditional risk factors. It is wise to be vigilant of this complication for timely intervention and better treatment outcomes.

Interrelationships among platelet-activating factor and lipoprotein-associated phospholipase A2 activity and traditional cardiovascular risk factors.

Traditionally cardiovascular disease (CVD) risk has been assessed through blood lipids and inflammatory marker C-reactive protein (hsCRP). Recent clinical interest in novel pro-inflammatory markers platelet-activating factor (PAF) and lipoprotein-associated phospholipase A2 (Lp-PLA2 ) recognizes that vascular damage can exist in the absence of traditional risk factors. This cross-sectional study investigated the potential relationship between circulating PAF, Lp-PLA2 , hsCRP, and traditional risk factors for CVD. One hundred adults (49 ± 13 years, 31% male) with variable CVD risk were recruited. Fasting inflammatory markers PAF, Lp-PLA2 and hsCRP and total, high-density lipoprotein (HDL), low-density lipoprotein (LDL) cholesterol, and triglycerides were measured. Blood pressure, body mass index, and waist circumference were measured. Medical and physical activity data were self-reported. Linear and multiple regressions were performed. PAF, Lp-PLA2 , and hsCRP independently correlated with several CVD risk factors. PAF was correlated significantly with risk factors in an unexpected way; there was a medium positive correlation between PAF and HDL cholesterol (r= 0.394, p< 0.001) and medium negative correlations with Total:HDL cholesterol; (r= -0.436, p< 0.001) systolic blood pressure; (r= -0.307, p= 0.001); BMI (r= -0.381, p< 0.001); and waist circumference (r= -0.404, p< 0.001). There were large positive correlations between Lp-PLA2 and LDL (r= 0.525, p< 0.001) and non-HDL cholesterol (r= 0.508, p< 0.001). There were large positive correlations between hsCRP and Total:HDL cholesterol (r= 0.524, p< 0.001); BMI (r= 0.668, p< 0.001); and waist circumference (r= 0.676, p< 0.001). PAF, Lp-PLA2 , and hsCRP are implicated in the pathophysiology of inflammation in CVD; however, the relationships between each marker and traditional risk factors were different suggesting they may be involved in different atherogenic pathways.

Correlation between Microalbuminuria and Coronary Angiographic Severity in Non-diabetic Myocardial Infarction patients

Background: Microalbuminuria may have an association with myocardial infarction in absence of traditional risk factors like diabetes. The present study was intended to find the association between microalbuminuria and angiographic severity of coronary artery disease in non-diabetic myocardial infarction patients. Methods: This cross sectional analytical study included 105 non-diabetic patients with myocardial infarction who underwent coronary angiography (CAG). The microalbuminuria was defined as urine albumin to creatinine ratio (ACR) of 30 -300 mg/g, while angiographic severity was measured by Gensini score with score e” 36 was taken as moderate to severe coronary artery disease (Group I) and score below 36 was termed as absent or mild coronary artery disease (Group II). Association of microalbuminuria with severity of coronary artery disease was determined. Results: Presence of microalbuminuria was found significantly higher (45%) in patients with moderate to severe coronary artery disease than that in patients with absent or mild CAD (4.6%). The Odds of having moderate to severe coronary artery disease in patients with microalbuminuria was observed to be 17 times (95% CI = 4.5 - 63) higher than that in patients without having this condition. Correlation between ACR and Gensini score was also found a significant positive relationship (r=0.702, p&lt;0.001) with 70% of variation in Gensini score being explained by ACR. Conclusion: Microalbuminuria can be considered as a predictor of the severity of coronary artery disease in non-diabetic myocardial infarction patients. Cardiovasc j 2022; 15(1): 56-62

Clonal hematopoiesis of indeterminate potential in patients with acute coronary syndrome undergoing percutaneous coronary intervention in the absence of traditional risk factors.

To investigate the frequency of clonal hematopoiesis of indeterminate potential (CHIP) and evaluate its impacts on outcomes in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) in the absence of traditional cardiovascular risk factors (CVRFs). Whole-exome sequencing was performed to detect the presence of CHIP in 183 patients underwent PCI for the treatment of ACS. The association between CHIP-related mutations and major adverse cardiac or cerebral events (MACCEs, a composite of all-cause mortality, coronary revascularization, myocardial infarction, or stroke) was analyzed in such cohort. Of 179 patients [median age, 65years; 84 female (46.9%)] included in this analysis, CHIP-related mutations were detected in 36 (20.1%) patients. The somatic mutations most frequently occurred in the genes DNMT3A (17 mutations), TET2 (6 mutations), and ASXL1 (4 mutations). Clinical outcomes at median 635 follow-up days showed that DNMT3A/TET2/ASXL1-CHIP mutations were associated with significantly higher risk of MACCEs, compared with non-CHIP carriers in the CVRFs-absent ACS cohort (26.1% vs. 4.2%, log-rank P = 0.001). Multivariable regression showed that DNMT3A/TET2/ASXL1-CHIP driver mutations (HR 4.015; 95% CI 1.236-13.046; P = 0.021) were independent predictors of adverse clinical outcomes. The most frequent CHIP-related mutations, DNMT3A, TET2, and ASXL1 are significantly associated with increased risk of recurrent cardiovascular events. Our study may be valuable target to reduce residual risk in patients with ACS carrying specific mutations.

Clinical Manifestations and Diagnosis of Pulmonary Embolism in Routine Clinical Practice: Data from the Ryazan Regional Vascular Center

BACKGROUND: Data on the peculiarities of the clinical presentation and characteristics of pulmonary embolism (PE) and problems of its diagnosis in routine clinical practice (CP) are limited. Data obtained long ago are mostly described in terms of venous thromboembolism in general and practically do not include Russian patients with PE. The study was performed within the RusSIan REgistery of pulmoNAry embolism (SIRENA) register.&#x0D; AIM: To study the peculiarities of the clinical and demographic profile and diagnosis of PE in modern CP in comparison with the results of other PE registers.&#x0D; MATERIALS AND METHODS: In this registry-based study, medical records were analyzed to obtain information on the demographic profile, clinical presentation, and examination results of patients with PE (n = 107; age, 63 (5274) years; men, 39.3%) who received inpatient treatment in one of the Ryazan Regional Vascular centers. The study period was 13 months (20182019).&#x0D; RESULTS: The most common concomitant pathologies were arterial hypertension (70.1%), obesity (46.7%), and diabetes mellitus (17.8%). High- and moderate-risk factors were identified in 26.2% and 72.9% of the patients, respectively. Low-risk factors identified in 5.6% of the patients in different combinations did not have a single risk factor for PE development. Clinical manifestations included shortness of breath (93.5%), chest pain (43.0%), severe weakness (59.8%), tachycardia (29.0%), hypoxemia (27.1%), and unstable hemodynamics (18.7%). The most frequent electrocardiographic sign was a T-wave inversion in the right chest leads (52.3%). Right ventricle dysfunction was detected in 38.1% of the cases and elevation of troponin levels in 33.6%. According to the Pulmonary Embolism Severity Index scale, high- and very-high-risk cases accounted for 46.7% of the cases. According to the results of the integrated assessment of PE severity, 34.6% and 14.0% of the patients moved to the lower- and higher-risk classes, respectively. The proportion of moderate-risk cases increased from 23.4% to 62.6%, and the high- and very-high-risk cases reduced from 46.7% to 32.0%.&#x0D; CONCLUSION: The modern clinical picture of PE is characterized by a higher prevalence of concomitant pathology and reduction of the rates of traditional risk factors. There remain difficulties in PE diagnosis, which are associated with the concomitant pathology, absence of traditional risk factors, and non-specificity of the clinical manifestations and results of additional examinations.

Clinical and Biologic Characteristics and Outcomes in Young and Middle-Aged Patients With Laryngeal Cancer: A Retrospective Cohort Analysis.

To describe the clinical and biologic characteristics and outcomes of young and middle-aged (YMA; <65 years) patients according to the presence or absence of traditional risk factors for laryngeal cancer. Retrospective cohort analysis. Single-institution academic medical center. Patients without a history of clinically significant tobacco use or heavy alcohol use were defined as "nontraditional": ≤5 pack-years, ≤5 years smoked, ≤14 alcoholic drinks per week, and ≥15-year interval from last tobacco abuse use to diagnosis. Remaining patients were categorized as "traditional." Select tumor samples were evaluated for bacterial and viral DNA by multiplex polymerase chain reaction. Seventy-eight YMA patients with primary laryngeal squamous cell carcinoma were identified, 23% (n = 18) of whom were nontraditional. Nontraditional patients were younger than traditional patients (median age, 51 vs 59 years; P < .001). Twenty-eight tumors were prospectively tested for human papillomavirus (HPV), and nontraditional patients were more likely to exhibit high-risk HPV (57% vs 5%, P < .01). Among 17 select tumors (nontraditional, n = 8; traditional, n = 9), 35% exhibited HPV16 (nontraditional, 63%; traditional, 11%; P = .05). Other viruses were identified but did not differ according to risk status: herpesviruses (40%) and Merkel cell polyomavirus (7%). Chlamydia, β-HPV, and γ-HPV DNA was not detected in any samples. Median length of follow-up was 42 months. On adjusted analyses, nontraditional patients exhibited nonsignificantly improved overall survival (hazard ratio, 0.24 [95% CI, 0.03-1.82]; P = .17) and disease-free survival (hazard ratio, 0.34 [95% CI, 0.10-1.23]; P = .08) as compared with traditional patients. Almost one-quarter of YMA patients lacked characteristic risk factors for laryngeal squamous cell carcinoma, and their tumors exhibited a higher prevalence of high-risk HPV. The significance of HPV16 and other tumor viruses with outcomes in nontraditional patients should be evaluated further.

Comparative Host-Pathogen Interaction Analyses of SARS-CoV2 and Aspergillus fumigatus, and Pathogenesis of COVID-19-Associated Aspergillosis.

COVID-19 caused a global catastrophe with a large number of cases making it one of the major pandemics of the human history. The clinical presentations of the disease are continuously challenging healthcare workers with the variation of pandemic waves and viral variants. Recently, SARS-CoV2 patients have shown increased occurrence of invasive pulmonary aspergillosis infection even in the absence of traditional risk factors. The mechanism of COVID-19-associated aspergillosis is not completely understood and therefore, we performed this system biological study in order to identify mechanistic implications of aspergillosis susceptibility in COVID-19 patients and the important targets associated with this disease. We performed host–pathogen interaction (HPI) analysis of SARS-CoV2, and most common COVID-19-associated aspergillosis pathogen, Aspergillus fumigatus, using in silico approaches. The known host–pathogen interactions data of SARS-CoV2 was obtained from BIOGRID database. In addition, A. fumigatus host–pathogen interactions were predicted through homology modeling. The human targets interacting with both pathogens were separately analyzed for their involvement in aspergillosis. The aspergillosis human targets were screened from DisGeNet and GeneCards. The aspergillosis targets involved in both HPI were further analyzed for functional overrepresentation analysis using PANTHER. The results indicate that both pathogens interact with a number of aspergillosis targets and altogether they recruit more aspergillosis targets in host–pathogen interaction than alone. Common aspergillosis targets involved in HPI with both SARS-CoV2 and A. fumigatus can indicate strategies for the management of both conditions by modulating these common disease targets.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00248-021-01913-6.

Time dependent deterioration of mitochondrial oxidative capacity in heart transplantat recipients with type 2 diabetes mellitus

Abstract Background Diabetic cardiomyopathy is defined as Heart failure in patients with Type 2 Diabetes (T2DM) in absence of traditional risk factors. Following HTX, a substantial number of recipients develop insulin resistance or T2DM, associated with cardiac allograft vasculopathy and with increased mortality. Recently we have shown that endomyocardial biopsies of heart transplant (HTX) recipients with T2DM express reduced mitochondrial respiration. Purpose The current study analyses time depended impact of T2DM on myocardial mitochondrial respiration of a priorly non-diabetic heart. We hypothesized that myocardial mitochondrial oxidative phosphorylation capacity declines in patients with T2DM compared to glucose tolerant heart transplant recipients and that reduced mitochondrial respiration leads to impairment of cardiac function. Methods We included 101 HTX recipients who underwent routine endomyocardial biopsy. Patients with T1DM or a Donor with DM were excluded. Patients were classified according to criteria of the American Diabetes Association as non-diabetic (n=23), prediabetic (n=38) or T2DM (n=40), by either Fasting Plasma Glucose, 2h Plasma Glucose, HbA1c or intake of antidiabetic medication. We performed ex vivo high resolution respirometry on permeabilized fibres to assess myocardial mitochondrial respiration. Left ventricular ejection fraction (LV-EF) was assessed by cardiac-MRI or Echocardiography. Results Groups were of comparable age (p=0.06), sex (p=0.25) and time since HTX (p=0.91). Mean time since HTX was 29 months. Current rejection episodes (p=0.37) or corticoid pulse therapy (p=0.46) did not significantly differ between groups. Linear regression in T2DM patients revealed an inverse relationship between time since HTX and mitochondrial respiration at state III conditions supported by the substrates octanoyl-carnitine and ADP (R2=0.16, F(1,38)=6.97, p=0.01). Regression analyses for non-DM group and Prediabetes group revealed no significant relationship between time since HTX and mitochondrial function (non-DM: R2=0.04, F(1,21)=0.9, p=0.35; Prediabetes: R2=0.01, F(1,36)=0.27, p=0.61). Exclusion of patients with cellular allograft rejection (ISHLT ≥1) or of patients with recent corticoid pulse therapy did not alter these results. Linear correlation revealed a significant relationship (r=0.33, p=0.04) between declining mitochondrial state III respiration and left ventricular ejection fraction (n=39), suggesting associated functional consequences. Conclusions Our results suggest a T2DM associated decline of mitochondrial oxidative capacity in HTX recipients. Reduced mitochondrial respiration is associated to lower LV-EF. Targeting mitochondrial respiration might be a promising novel therapeutic approach to address T2DM associated mortality. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): German Research Counsil

Recurrent acute pancreatitis during a ketogenic diet\u2014a case report and literature review

BackgroundThe ketogenic (“keto”) diet has been gaining more attention lately in the medical literature and the lay media as a potentially effective method for weight control and management of type 2 diabetes. Though rare, there have been case reports of serious side effects. Here, we present a peculiar case of pancreatitis presumably associated with the ketogenic diet.Case presentationA 35-year-old man on a calorie-restricted ketogenic diet presented to the emergency department with weekly abdominal pain on Monday mornings, each time after dietary indiscretions (“cheat days”) on the weekend. It was found that he had a clinical presentation consistent with acute pancreatitis with no associated alcohol use, hypertriglyceridemia, pancreatic obstruction, or other anatomic abnormalities. The patient’s symptoms resolved with conservative management and progressive reintroduction of a standard diet.ConclusionThis case indicates that the ketogenic diet could lower the threshold for acute pancreatitis, and that an episodic stressor may trigger an acute attack in the absence of traditional risk factors.

Coronary artery disease in the absence of traditional risk factors: a call for action.

We examined the 256 clinical trials underpinning the two current international ST-elevation myocardial infarction (ST EMI) management guidelines to ascertain the proportion of trials that reported patients with no standard modifiable risk factors as a separate group. We examined the 256 clinical trials underpinning the two current international ST-elevation myocardial infarction (ST EMI) management guidelines to ascertain the proportion of trials that reported patients with no standard modifiable risk factors as a separate group.