Third-Degree Atrioventricular Block And Asystole After Lung Resection: A Rare Complication.

Surgical resection remains the optimal therapeutic option for early-stage operable NSCLC. Despite significant advances in recent years related to anesthetic and surgical techniques, cardiopulmonary complications remain major causes for postoperative morbimortality. In this paper we present a case of a patient who developed complete AV block followed by asystole after lung resection surgery. The patient underwent surgery via right VATS and the procedure was uneventful.  On the first post-operative day patient developed a third-degree atrioventricular block followed by 6 seconds asystole. Pharmacological treatment was instituted and implementation of a permanent pacemaker occurred on the third post-operative day, without complications. The remaining postoperative course was uneventful and the patient was discharged home on the sixth post-operative day. It is the objective of the authors to report and highlight this rare and potencial fatal complication of lung resection.

Interaction Between Risk Factors, Coronary Calcium, and CCTA Plaque Characteristics in Patients Age 18-45.

AIMS: The atherosclerotic profile and advanced plaque subtype burden in symptomatic patients ≤45 years old have not been established. This study aimed to assess the prevalence and predictors of coronary artery calcium (CAC), plaque subtypes, and plaque burden by coronary computed tomography angiography (CCTA) in symptomatic young patients. METHODS AND RESULTS: We included 907 symptomatic young patients (18-45 years) from Montefiore undergoing CCTA for chest pain evaluation. Prevalence and predictors of CAC, plaque subtypes, and burden were evaluated using semi-automated software. In the overall population (55% female and 44% Hispanic), 89% had CAC = 0. The likelihood of CAC or any plaque by CCTA increased with >3 risk factors (RF, OR 7.13 [2.14-23.7] and OR 10.26 [3.36-31.2], respectively). Any plaque by CCTA was present in 137 (15%); the strongest independent predictors were age ≥35 years (OR 3.62 [2.05-6.41]) and family history of premature CAD (FHx) (OR 2.76 [1.67-4.58]). Stenosis ≥50% was rare (1.8%), with 31% of those having CAC = 0. Significant non-calcified (NCP, 37.2%) and low-attenuation (LAP, 4.24%) plaque burdens were seen, even in those with non-obstructive stenosis. Among patients with CAC = 0, 5% had plaque, and the only predictor of exclusively non-calcified plaque was FHx (OR 2.29 [1.08-4.86]). CONCLUSIONS: In symptomatic young patients undergoing CCTA, the prevalence of CAC or any coronary atherosclerosis was not negligible, and the likelihood increased with RF burden. The presence of coronary stenosis ≥50% was rare and most often accompanied by CAC > 0 but there was a significant burden of NCP and LAP even within the non-obstructive group.

Impact of Hyperuricemia and Urate-Lowering Agents on Cardiovascular Diseases.

The association between hyperuricemia and cardiovascular diseases has been studied for many years. Research has shown a link between high uric acid levels and increased risk of including coronary artery disease hypertension and other cardiovascular conditions. Urate-lowering therapy, particularly with xanthine oxidase inhibitors like allopurinol, has shown promising results in reducing blood pressure in individuals with hyperuricemia and hypertension. Clinical trials and studies have demonstrated significant reductions in both systolic and diastolic blood pressure with urate-lowering treatment. Urate-lowering treatment has shown a favorable effect on reducing systolic blood pressure and major adverse cardiovascular events in patients with previous cardiovascular disease. In terms of cardiovascular safety, clinical trials have indicated that xanthine oxidase inhibitors such as febuxostat are non-inferior to allopurinol and do not increase the risk of death or serious adverse events. Overall, these findings highlight the importance of managing hyperuricemia and utilizing urate-lowering therapy to mitigate the adverse cardiovascular effects associated with elevated uric acid levels.

A Successful Treatment of COVID-Induced Acute Idiopathic Pancreatitis with an RNA-Polymerase Inhibitor Agent.

Acute idiopathic pancreatitis (AIP) has been rarely linked to SARS-CoV-2 and its mechanism is not completely understood. As a result, its management, due to the heterogeneity of the literature, may pose a challenge. This case report describes a 59-year-old female who presented to the emergency department with severe epigastric pain, fever, and a positive SARS-CoV-2 polymerase chain reaction (PCR) test. Imaging confirmed acute interstitial pancreatitis, which was successfully managed using the viral RNA polymerase inhibitor, remdesivir. Pancreatitis-associated complications, such as sepsis and shock, are recognized as significant factors contributing to extended hospitalization and increased mortality rates. The management of autoimmune pancreatitis poses a challenge due to the diverse existing literature, resulting in a lack of standardized approaches. Although the impact on inpatient mortality of remdesivir remains uncertain, early administration of RNA polymerase inhibitors could alleviate complications and positively impact the duration of hospitalization. Further research is important to create optimal management strategies for complications related to COVID-19-related pancreatitis.

Outcomes Of Surgically Treated N2-Positive Non-Small Cell Lung Cancer.

INTRODUCTION: The role of surgery in the treatment of stage IIB/IIIA lung cancer is still a matter of debate. To assess the outcomes of N2-positive patients, we performed a retrospective 10-year study including all patients with histologically proven N2 disease submitted to lung resection surgery by the same surgical team in three different hospitals. MATERIALS AND METHODS: Demographic, clinical, surgical and survival data were collected from patients' clinical registries. Patients were divided into groups according to evidence of neoadjuvant chemotherapy and number of positive N2 stations. Outcomes regarding survival time within and between groups were calculated and compared. RESULTS: Sixty-four patients were included in our study, with a mean age of 62,2 years. Surgery was performed by uniportal VATS in 43.8% of cases. A mean of 3 nodal stations were sampled and 35 patients (54.7%) had one single positive N2 station. Post-operative complications occurred in 27% of patients but no post-operative mortality was recorded. Twenty-seven patients (42.2%) were submitted to neoadjuvant chemotherapy. Survival time within this group was of 67,7±10,5 months, which was not statistically different from those who performed upfront surgery (survival time 48±5,2 months). Patients with single N2 positive stations had a longer survival time than those with multiple N2 positive stations (p<0.05). Within the group of patients with single N2 disease (n=35), no difference in survival time was found regarding neoadjuvant therapy. CONCLUSIONS: Surgery is effective in selected patients with N2 disease, in particular those with single-N2 positive stations. Neoadjuvant chemotherapy may not grant survival benefit. Adequate pre-operative staging is essential.

Crochetage, the Forgotten Electrocardiographic Sign.

Acquired complete heart block is a rare but severe arrhythmia caused by various factors such as infections, medications, and autoimmune conditions. Atrial septal defect (ASD) is a common congenital heart defect, with larger ASDs possibly causing symptoms such as fatigue, shortness of breath, and frequent respiratory infections. In some cases, high-grade atrioventricular block with ASD can occur; however, the exact incidence is not well established. We report a rare case of a 15-year-old male presenting with acute dizziness. Initial electrocardiogram (EKG) showed a complete heart block with a Crochetage sign. Patent foramen ovale (PFO) was confirmed by transthoracic and transesophageal echocardiograms. Closure of PFO and permanent pacemaker resulted in complete resolutions of symptoms and disappearance of Crochetage sign.

Role of genetic polymorphisms in clopidogrel response variability: a systematic review.

INTRODUCTION: Clopidogrel is a P2Y12 inhibitor that has become a mainstay treatment following percutaneous intervention with drug-eluting stent placement to decrease restenosis and its potential complications, including sudden cardiac death and ischaemic strokes in patients with significant vascular disease. AREAS COVERED: As a prodrug, the metabolism and efficacy of clopidogrel are contingent on the presence of wild-type CYP450 (CYP2C19) alleles. Genetic polymorphisms and variants are well known to impair its ability to prevent major adverse cardiovascular events in these patients, with inadequate response rates as high as 30% in previous publications. Patterns of allelic frequencies are expected to exhibit similarities between individuals of the same ancestry, ethnic group or geographic region. Accordingly, we seek to further elucidate worldwide prevalence rates for genetic polymorphisms in the CYP2C19-dependent metabolism of clopidogrel and review the potential of personalised CYP2C19 genotyping in clinical practice to mitigate this high treatment resistance and its associated burden on patients. EXPERTS' COMMENTARY: Our findings support the consideration of genotyping before initiation of therapy to guide adequate dosage or substitutions of other P2Y12 inhibitors to promote personalised, precision medicine and to prevent adverse events when these therapies may inevitably fail in patients with variants of the CYP450 (CYP2C19) system.

Six-minute rowing test: a practical tool for training prescription, from ventilatory thresholds and power outputs, in amateur male rowers.

Background: The 6-minute rowing ergometer test (6-minRT) is valid and reliable for establishing maximal aerobic power (MAP) in amateur male rowers. However, ventilatory thresholds (VTs) have not yet been established with their mechanical correspondence in this test. Objective: The primary objective was to determine the VTs in the 6-minRT achieved by amateur male rowers, while the secondary objective was to determine the correspondence between ventilatory, mechanical, and heart rate (HR) outcomes of the 6-minRT. Methods: Sixteen amateur male rowers were part of the study. All participants were instructed to perform an incremental test (IT) and a 6-minRT. Determination of the ventilatory parameters for the first ventilatory threshold (VT1), the second ventilatory threshold (VT2), and 6minRTVO2max were performed by correlating the outcomes of VT1, VT2, and VO2max obtained in the IT, with the outcomes of 6-minRT. For these purposes, Pearson's test was used, with the following criteria: trivial, <0.1; small, 0.1-0.3; moderate, 0.3-0.5; high, 0.5-0.7; very high, 0.7-0.9; or practically perfect, >0.9. The significance level was p < 0.05. Results: The IT analysis determined that VT1 and VT2 correspond to 55 and 80% of VO2max, respectively. A high correlation was observed between IT outcomes in VT1, VT2, and VO2max, with the outcomes of 6-minRT (r > 0.6). Conclusion: Based on IT ventilatory parameters and concordance analysis, VT1 and VT2 of 6-minRT are determined at 55 and 80%, respectively, of both ventilatory parameters and their corresponding mechanical outcomes and HR.

COVID-19-Induced Cardiac Tamponade: A Case Study and a Literature Review.

COVID-19 presentation is heterogeneous. As a viral illness, it could cause pericardial effusion leading to cardiac tamponade. We present a patient coursing with this viral illness that was found to have cardiac tamponade. We report a case of a 79-year-old female who presented with shortness of breath and dry cough for one week and resulted positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Her initial chest X-ray showed a bottle-shaped heart. Computed chest tomography showed pericardial effusion, and an echocardiogram confirmed moderated pericardial effusion with signs of tamponade. He improved with conservative therapy with colchicine, ibuprofen, cefepime, dexamethasone, dolutegravir, and apixaban for pulmonary emboli. An early approach in cardiac tamponade induced by COVID-19 is crucial to promptly address an aggressive directed therapy, avoiding potential complications or unnecessary procedures.

Interplay Between Zero CAC, Quantitative Plaque Analysis, and Adverse Events in a Diverse Patient Cohort.

BACKGROUND: Coronary artery calcium scoring (CAC) has garnered attention in the diagnostic approach to chest pain patients. However, little is known about the interplay between zero CAC, sex, race, ethnicity, and quantitative coronary plaque analysis. METHODS: We conducted a retrospective analysis from our computed tomography registry of patients with stable angina without prior myocardial infarction or revascularization undergoing coronary computed tomography angiography at Montefiore Healthcare System. Follow-up end points collected included invasive angiography, type-1 myocardial infarction, coronary revascularization, cardiovascular and all-cause death. RESULTS: A total of 2249 patients were included (66% female). The median follow-up was 5.5 years. The median age of those without CAC was 52 years (interquartile range, 44-59) and 60 years (interquartile range, 53-68) in those with CAC. Most patients were Hispanic (58%), and the rest were non-Hispanic Black (28%), non-Hispanic White (10%), and non-Hispanic Asian (5%). The majority had CAC=0 (55%). The negative predictive value of CAC=0 was 92.8%, 99.9%, and 99.9% for any plaque, obstructive coronary artery stenosis, and the composite outcome of all-cause death, myocardial infarction, or coronary revascularization, respectively. Among patients without CAC (n=1237), 89 patients (7%) had evidence of plaque on their coronary computed tomography angiography with a median low-attenuation noncalcified plaque burden of 4% (2-7). There were no significant differences in the negative predictive value for CAC=0 by sex, race, or ethnicity. Patients with ≥2 risk factors had higher odds of having plaque with zero CAC. CONCLUSIONS: In summary, no sex, race, or ethnicity differences were demonstrated in the negative predictive value of a zero CAC; however, patients with ≥2 risk factors had a higher prevalence of plaque. A small percentage (7%) of symptomatic patients undergoing coronary computed tomography angiography with zero CAC had noncalcified coronary plaque, with the implication that caution is needed for downscaling of preventive treatment in patients with zero CAC, chest pain, and multiple risk factors.

Somatic Embryogenesis in Conifers: One Clade to Rule Them All?

Somatic embryogenesis (SE) in conifers is usually characterized as a multi-step process starting with the development of proembryogenic cell masses and followed by histodifferentiation, somatic embryo development, maturation, desiccation, and plant regeneration. Our current understanding of conifers' SE is mainly derived from studies using Pinaceae species as a model. However, the evolutionary relationships between conifers are not clear. Some hypotheses consider conifers as a paraphyletic group and Gnetales as a closely related clade. In this review, we used an integrated approach in order to cover the advances in knowledge on SE in conifers and Gnetales, discussing the state-of-the-art and shedding light on similarities and current bottlenecks. With this approach, we expect to be able to better understand the integration of these clades within current studies on SE. Finally, the points discussed raise an intriguing question: are non-Pinaceae conifers less prone to expressing embryogenic competence and generating somatic embryos as compared to Pinaceae species? The development of fundamental studies focused on this morphogenetic route in the coming years could be the key to finding a higher number of points in common between these species, allowing the success of the SE of one species to positively affect the success of another.

Assessment of calcinosis in Portuguese patients with systemic sclerosis - a multicenter study.

INTRODUCTION/OBJECTIVES: The study aims to define the clinical and subclinical calcinosis prevalence, the sensitivity of radiographed site and clinical method for its diagnosis, and the phenotype of Portuguese systemic sclerosis (SSc) patients with calcinosis. METHOD: A cross-sectional multicenter study was conducted with SSc patients fulfilling Leroy/Medsger 2001 or ACR/EULAR 2013 classification criteria, registered in the Reuma.pt. Calcinosis was assessed through clinical examination and radiographs of hands, elbows, knees, and feet. Independent parametric or non-parametric tests, multivariate logistic regression, and sensitivity calculation of radiographed site and clinical method for calcinosis detection were performed. RESULTS: We included 226 patients. Clinical calcinosis was described in 63 (28.1%) and radiological calcinosis in 91 (40.3%) patients, of which 37 (40.7%) were subclinical. The most sensitive location to detect calcinosis was the hand (74.7%). Sensitivity of the clinical method was 58.2%. Calcinosis patients were more often female (p = 0.008) and older (p < 0.001) and had more frequently longer disease duration (p < 0.001), limited SSc (p = 0.017), telangiectasia (p = 0.039), digital ulcers (p = 0.001), esophageal (p < 0.001) and intestinal (p = 0.003) involvements, osteoporosis (p = 0.028), and late capillaroscopic pattern (p < 0.001). In multivariate analysis, digital ulcers (OR 2.63, 95% CI 1.02-6.78, p = 0.045) predicted overall calcinosis, esophageal involvement (OR 3.52, 95% CI 1.28-9.67, p = 0.015) and osteoporosis (OR 4.1, 95% CI 1.2-14.2, p = 0.027) predicted hand calcinosis, and late capillaroscopic pattern (OR 7.6, 95% CI 1.7-34.9, p = 0.009) predicted knee calcinosis. Anti-nuclear antibody positivity was associated with less knee calcinosis (OR 0.021, 95% CI 0.001-0477, p = 0.015). CONCLUSIONS: Subclinical calcinosis high prevalence suggests that calcinosis is underdiagnosed and radiographic screening might be relevant. Multifactorial pathogenesis may explain calcinosis predictors' variability. Key Points • Prevalence of subclinical calcinosis in SSc patients is substantial. • Hand radiographs are more sensitive to detect calcinosis than other locations or clinical method. • Digital ulcers were associated with overall calcinosis, esophageal involvement and osteoporosis were associated with hand calcinosis, and late sclerodermic pattern in nailfold capillaroscopy was associated with knee calcinosis. • Anti-nuclear antibody positivity may be a protective factor for knee calcinosis.

The Role of Lung Ultrasound in Systemic Sclerosis: A Systematic Review.

BACKGROUND: In systemic sclerosis (SSc), high-resolution computed tomography (HRCT) of the chest is the standard criterion for the diagnosis of interstitial lung disease (ILD). However, recent evidence suggests that lung ultrasound (LUS) can also detect ILD, without radiation exposure. Thus, our goal was to perform a systematic review, aiming to clarify the role of LUS in the detection of ILD in SSc. METHODS: A systematic review was carried out in PubMed and EMBASE (PROSPERO register number CRD42022293132), to identify studies that compared LUS with HRCT in the detection of ILD in patients with SSc. Risk of bias was assessed with the QUADAS-2 () tool. RESULTS: Three hundred seventy-five publications were identified. After screening, 13 were included in the final analysis. No study presented high risk of bias. Lung ultrasound protocol was highly heterogeneous between authors, specifically concerning transducer, intercostal spaces evaluated, exclusion criteria, and definition of positive LUS. Most authors evaluated the presence of B-lines as a surrogate of ILD, with only 4 focusing on pleural changes. A positive correlation between LUS findings and ILD detected by HRCT was reported. Results also revealed high sensitivity (74.3%-100%) but variable specificity (16%-99%). Positive predictive value varied between 16% and 95.1%, and negative predictive value between 51.7% and 100%. CONCLUSION: Lung ultrasound is sensitive in the detection of ILD, but specificity must be optimized. The value of pleural evaluation also requires further investigation. Moreover, a consensus is needed to define a uniform LUS protocol to implement in future investigations.

Severe Liver Injury Secondary to COVID-19-Induced Rhabdomyolysis in McArdle Disease.

Severe liver injury is an uncommon condition caused by non-traumatic rhabdomyolysis. This rare correlation is more commonly seen in the aspartate aminotransferase (AST) than in the alanine transaminase (ALT) level elevation. We report a case of a 27-year-old male with a history of McArdle disease who presented with generalized muscle aches associated with dark urine. His workup showed SARS-CoV-2 positive, severe rhabdomyolysis (creatinine kinase [CK] > 40000 U/L) and acute kidney injury (AKI) followed by severe liver injury (AST/ALT: 2122/383 U/L). He was started on aggressive intravenous hydration. After multiple boluses, he became overloaded, fluids were re-adjusted and continued, his renal function, CK, and liver enzymes improved, and the patient was discharged; during his visit at the post-discharge, the patient was asymptomatic and no clinical or laboratory abnormalities were found. The glycogen storage diseases are challenging, but prompt and accurate assessment is determinant in recognizing potential life-threatening complications of SARS-CoV-2. The failure to identify complicated rhabdomyolysis could lead to the patient's rapid deterioration, ending in multiorgan failure.

Osteolysis in Systemic Sclerosis: A Scoping Review.

OBJECTIVE: To perform a scoping review focusing on osteolysis in systemic sclerosis (SSc). METHODS: This review was performed in line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) recommendations. RESULTS: From a total of 351 results, 29 articles were included for the final analysis. The publications included proved to be heterogeneous regarding the population and inclusion criteria. The lack of a standardized method of detection of osteolysis further enhanced these inequalities. Most studies reported location/prevalence of osteolysis and associations with other manifestations, with only a minority focusing on topics like predictors of osteolysis and its prognostic value. None of the authors addressed treatment approach. The most frequently analyzed and prevalent location was acro-osteolysis (AO). Diffuse cutaneous subtype and anti-topoisomerase I antibody correlated positively with AO. Disease duration, calcinosis, and digital ischemia were the features more frequently associated with AO, but only the last 2 predicted AO. Ultrasound showed high sensitivity for detection of AO. CONCLUSION: Despite the effect that osteolysis has on patients with SSc, there is a significant lack of studies on this area. Notably, there are no studies that we know of focused on treatment. Also, there is a lack of longitudinal studies that would allow a reliable assessment of its prognostic value and predictors.

Enzymatic Antioxidant System Activation Assures the Viability of Guadua chacoensis (Bambusoideae, Poaceae) Embryogenic Cultures during Cryopreservation.

This study aimed to establish a cryopreservation protocol for G. chacoensis embryogenic cultures (ECs) and to investigate the role of antioxidant enzymes activities during cryopreservation. The growth dynamics of cell suspensions were also investigated, followed by a phytotoxicity test to assess the ECs' ability to tolerate the use of cryoprotective solutions for different incubation times (0, 30, 60, 120, and 240 min). We evaluated the EC redox state in three steps of cryopreservation: after incubation in cryoprotection solution, after thawing, and 60 days after regrowth. Our results showed that the ECs support the use of cryoprotective solution until 120 min, showing phytotoxic effects with 240 min of incubation. This study reports a 100% survival of the cultures and a 10% increase ratio in fresh material for both incubation times tested (60 and 120 min). Increased malonaldehyde content was identified after incubation in the cryoprotective solution. An increase in the activities of catalase and ascorbate peroxidase was also identified in the subsequent steps, suggesting that the activation of antioxidant enzymes is essential for maintaining cell homeostasis during cryopreservation.

COVID-19 therapy and vaccination: a clinical narrative review.

The SARS-CoV-2 pandemic is the most globally impacting health issue our world has faced over the last century. As of January 7, 2022, around 300 million cases have been reported worldwide, with over 5 million deaths. The SARS-CoV-2 infection causes a hyperactive host immune response leading to an excessive inflammatory reaction with the release of many cytokines - cytokine storm - commonly noticed in acute respiratory distress syndrome, sepsis and fulminant multiorgan failure. Since the beginning of the pandemic, the scientific medical community has worked on therapeutic procedures that interfere with the exaggerated immune response. Thromboembolic complications are widespread in patients who are critically ill with COVID-19. Anticoagulant therapy was initially considered a cornerstone in hospitalized patients and even in the early post-discharge period; however, later trials have aborted the clinical benefits except for suspicion of or confirmed thrombosis. Immunomodulatory therapies are still crucial in moderate to severe COVID-19. Immunomodulator therapies include various medications from steroids to hydroxychloroquine, tocilizumab and Anakinra. Anti-inflammatory agents, vitamin supplements and antimicrobial therapy had initial encouraging evidence, but there are limited data to review. Convalescent plasma, immunoglobulins, eculizumab, neutralizing IgG1 monoclonal antibodies and remdesivir have positively impacted inpatient mortality and hospital length of stay. Eventually, wide population vaccination was proven to be the best tool to overcome the SARS-CoV-2 pandemic and help humanity return to regular life. Many vaccines and various strategies have been used since December 2020. This review discusses how the SARS-CoV-2 pandemic has progressed and surged, and summarizes the safety and efficacy of the most used therapies and vaccines in the light of recent evidence.