Stress KillsBerhane Worku MD1, Shudhanshu Alishetti2, Kumudha Ramasubbu21. New York Presbyterian Brooklyn Methodist Hospital/Weill Cornell Medical Center Department of Cardiothoracic Surgery, Brooklyn, NY 112152. New York Presbyterian Brooklyn Methodist Hospital Division of Cardiology, Brooklyn NY 11215Corresponding AuthorBerhane Worku MDDepartment of Cardiothoracic SurgeryNew York Presbyterian Brooklyn Methodist Hospital506 6th StreetBrooklyn, NY 11215The medical, economic, and social consequences of the COVID-19 pandemic have been profound. Severe respiratory failure as well as inflammatory and thrombotic complications have resulted in hundreds of thousands of deaths. Political controversy continues regarding optimal strategies for large scale control of the pandemic. Social distancing policies have led to reduced transmission rates but the economic effects have been devastating. Optimal treatment strategies continue to evolve, and vaccine solutions are on the horizon. In addition to these more obvious issues, other severe consequences of the pandemic are slowly being recognized.In the current report, Kir et. al. describe two postmenopausal women presenting with signs and symptoms of acute coronary syndrome in the setting of severe psychological stress related to social isolation during the COVID-19 pandemic (1). Both were COVID negative and both had unremarkable coronary angiograms. Both were diagnosed with takotsubo cardiomyopathy based on the characteristic findings of angina, mild troponin elevation, electrocardiographic changes, and apical akinesis on echocardiogram. Both admitted to severe anxiety and stress in the days prior to the onset of symptoms. Both improved with conservative management including beta-blockers and anxiolytics with resolution of apical akinesis on follow up echocardiogram.Takotsubo or stress cardiomyopathy is a now well recognized entity typically presenting as angina or dyspnea in the setting of a severe emotional or physical stressor. Postmenopausal women are more frequently affected and a history of psychiatric disorders is frequently noted. Electrocardiographic abnormalities and mild troponin elevations are common. Diagnosis is based on the InterTAK diagnostic score. Echocardiography classically demonstrates apical ballooning with basal hyperkinesis, but other wall motion abnormalities are described usually extending beyond a traditional coronary artery distribution. Coronary angiography is frequently performed to rule out acute coronary syndrome but is unremarkable. The syndrome is typically self-limited, requiring conservative supportive management, but in severe cases can lead to heart failure and shock requiring high-dose pharmacologic support, mechanical circulatory support, and in ~5% of cases can be fatal (2).Emotional and physical stress are risk factors for a variety of conditions including cardiovascular disease. Furthermore, psychiatric disorders such as depression and anxiety are associated with poorer outcomes in the setting of cardiovascular disease. Proposed mechanisms for this include behavioral factors such as noncompliance with medications and lifestyle modifications (diet, exercise, smoking cessation). Biological factors are also suggested, including altered autonomic nervous system activity with elevations in catecholamine levels and inflammatory responses amongst others (3). Similar hypotheses have been put forth regarding the mechanism of takotsubo stress cardiomyopathy and perhaps some overlap exists between the cardiovascular manifestations of psychiatric disorders and overt stress cardiomyopathy.The COVID-19 pandemic has had several medical consequences beyond those related to viral infection itself. The suspension of certain medical and surgical services potentially allows for the natural history of various diseases to take their course. Unemployment impairs the ability of many to access what medical services remain available. Psychiatric disorders are inflamed in the setting of social, economic, and other stressors. A four to five-fold increase in the incidence of stress cardiomyopathy has been noted during the months following the COVID-19 outbreak unrelated to COVID-19 infection itself, presumably the consequence of stress related to the abovementioned effects of the pandemic and our response to it. (4). COVID-19 has taught us that stress kills.REFERENCESKir D, Beer N, De Marchena EJ. Takutsobo cardiomyopathy caused by emotional stressors in the Coronavirus Disease 2019 (COVID-19) pandemic era. J Card Surg in pressDe Chazal HM, Del Buono MG, Keyser-Marcus L, Ma L, Moeller FG, Berrocal D, Abbate A. Stress cardiomyopathy diagnosis and treatment. J Am Coll Cardiol 2018;72:1955-71Takagi H, Ando T, Umemoto. Perioperative depression or anxiety and postoperative mortality in cardiac surgery: a systematic review and meta-analysis. Heart Vessels 2017;32:1458-1468Jabri A, Kalra a, Kumar A, Alameh A, Adroja S, Bashir H, Nowacki AS, Shah R, Khubber S, Kanaa’N A, Hedrick DP, Sleik KM, Mehta N, Chung MK, Khot UN, Kapadia SR, Puri R, Reed GW. Incidence of stress cardiomyopathy during the coronavirus disease 2019 pandemic. JAMA Netw Open 2020 Jul 1;3(7):e2014780. doi: 10.1001/jamanetworkopen.2020.14780
Objectives: To compare pain, quality of life(QoL), sexual function and lower urinary tract symptoms(LUTS) between rigid(RC) and flexible cystoscopy(FC). Methods: Forty-one patients who were planned control cystoscopies were enrolled the study. At the first cystoscopy, 20 patients(Group 1) and other 21 patients(Group 2) were performed by using flexible(15,5Fr) and rigid cystoscope(15,5Fr), respectively. At the second cystoscopies, the patients in group 1 and group 2 were performed by using rigid and flexible cystosacope, respectively. In all the patients, pain was measured with visual pain scale(VPS) shortly after cystoscopy. Also SF, QoL and LUTS were assessed by using IIEF, SF-36 and MLUTS forms, respectively. Results: While 22 of the patients preferred FC, the other 19 preferred RC(p>0,05). There were no statistically differences between VPS, IIEF, SF-36 and MLUTS scores of the two groups. In multivariate analysis regarding quality of life, although sexual function, pain and cystoscopy type did not affect QoL, voiding symptoms affected independently QoL. After the both cystoscopy type, IIEF, SF-36 and MLUTS scores did not change statistically. Conclusion: The results showed that the effects on pain, sexual function, QoL and LUTS of RC and FC were similar. In general, cystoscopy did not affect negatively on QoL, sexual function and LUTS of the patients.
With the rapid increase of reported COVID-19 cases, German policymakers announced a 4-week “shutdown light” starting on Nov 2, 2020. Applying mathematical models, possible scenarios for the evolution of the outbreak in Germany are simulated. The results indicate that independent of the effectiveness of the current restrictive measures they might not be sufficient to mitigate the outbreak. Repeated shutdown periods or permanently applied measures over the winter could be successful alternatives.
COVID-19 and nuclear cardiology: Introducing the ‘’forward” virtual visit Angelidis G, Valotassiou V, Psimadas D, Georgoulias PNuclear Medicine Laboratory, University of Thessaly, Larissa, GreeceWe read with great interest the recent review article by Kaushik A, et al. concerning the potential role of digital health applications in the present pandemic situation . As the authors noted, alternative tools are needed for the optimal management of cardiovascular patients, avoiding unnecessary visits to health care facilities. The severe acute respiratory syndrome – coronavirus – 2 (SARS-CoV-2) can invade the cardiovascular cells, potentially causing life-threatening cardiac impairment . In particular, patients with pre-existing cardiovascular diseases are characterized by a higher risk of adverse cardiovascular events. Therefore, most of those referred for nuclear cardiology techniques are expected to be at higher risk of developing serious coronavirus disease 2019 (COVID-19) complications. However, the performance of the individually required diagnostic and follow-up procedures is important .Telemedicine applications have been used in public health emergencies, leading to several advantages in terms of safety and efficacy. In the field of nuclear cardiology, the initial evaluation of patients’ history and clinical features can take place remotely (‘’forward” virtual visit). This approach seems to be patient-centred (permitting an adequate case assessment) and conducive to self-quarantine (protecting patients, healthcare professionals, and the community from viral exposure). Importantly, possible clinical presentations of COVID-19 may be evaluated during the ‘’forward” virtual visit, as well as information regarding travel and exposure histories. Moreover, local epidemiological information may be used to adjust screening pattern, and special measures could be developed (such as isolation in dedicated ‘’hot” rooms) for patients with high-risk features. After the performance of the examination, telemedicine applications could be also used for the consultation with the patients.Telemedicine applications may contribute to a better adjustment of nuclear cardiology services under the current demanding circumstances. Of course, no telemedicine programme can be created overnight, but this approach may be of value not only during the next months but also after the end of COVID-19 pandemic . For example, our nuclear medicine laboratory is located in central Greece providing services to inhabitants of mountain villages, and nearby small islands. Consequently, the use of telemedicine applications could aid our practice in the future as well, particularly during the winter months when travelling by car or sea travels may be extremely demanding.
Editorial: Respiratory outcomes post Nusinersen in Spinal Muscular Atrophy Type 11 Kate Gonski1,2 Dominic A. FitzgeraldDepartment of Respiratory Medicine, The Children’s Hospital at Westmead, Sydney, NSW, Australia 2145Discipline of Child & Adolescent Health, Sydney Medical School, Faculty of Health Sciences, University of Sydney, NSW, Australia 2145Corresponding author:Dominic A. Fitzgerald MBBS PhD FRACPClinical Professor Child & Adolescent HealthDepartment of Respiratory MedicineThe Children’s Hospital at WestmeadLocked Bag 4001Westmead, NSWAustralia, 2145.1458 words15 referencesTime to wake up and smell the roses as the real world respiratory experiences have arrived for Spinal Muscular Atrophy type 1 (SMA1)! Nusinersen, the first drug to be approved for treatment of SMA1, has changed the natural history of the disease and has now been commercially available in many countries for up to four years(1). SMA 1, the most common cause of infant death attributed to respiratory insufficiency, results from a degeneration of alpha motor neurons in the spinal cord and brainstem resulting in progressive skeletal muscle weakness of the limbs, respiratory and bulbar muscles (2). Most patients with SMA1 will have respiratory complications in the first year of life requiring therapy to support airway clearance and ventilation (2). The pan-ethnic incidence is 1 in 11,000 births (3). Milder phenotypes occur as SMA types 2 and 3 in childhood with a much better prognosis (4) and countries may offer nusinersen for these patients also.In this issue, Lavie and colleagues (5) offer insights into clinicalrespiratory outcomes from 3 years of prospective data collection in their cohort of 20 SMA1 patients treated before and after 2 years of nusinersen in Israel. Their work builds on the scientific evidence of efficacy of nusinersen primarily for motor outcomes over the last decade. A phase 3 randomised, double-blinded, sham controlled clinical trial in patients with SMA 1 showed that those treated with nusinersen had a significant motor milestone response with a higher likelihood of event-free survival(6). This group did not show a difference in the frequency of serious respiratory adverse events between the groups, thereby leaving unanswered questions about the effect of the medication on respiratory morbidity. Over the past few years, the translatability of outcomes from randomized controlled studies to current real-world outcomes has been questioned (7-9).A letter to the editor by LoMauro et al. involving children with SMA1 described a milder subset of children with SMA 1 [Described as type SMA 1c: onset between 3 and 6 months] treated with nusinersen who had an improvement in accessory muscle use and reduced daily hours of ventilation when compared to a natural history cohort (7). This was not reported in the more severe SMA 1a and 1b groups. Sansone et al. (8) published an observational, longitudinal cohort study looking at respiratory support requirements at baseline, 6 months and 10 months after nusinersen treatments in 118 children with SMA1. Semi-structured qualitative interviews from caregivers were collected at each interval. They showed that 77% of the cohort’s respiratory requirements remained stable and more than 80% of children treated before 2 years survived in contrast to the lower survival reported in natural history studies. The limitation of this study is that they used modality and number of hours of ventilation as the surrogate for respiratory function which can be influenced significantly by respiratory care, management and patient compliance. Chen et al. (9) also published follow-up data (single-centre) in SMA 1 children treated with nusinersen in order to further understand the comprehensive real-world outcomes of this new treatment. While this study was limited by its small sample size of 9, it highlighted that children with SMA1 treated with nusinersen continued to develop considerable respiratory comorbidities. Although a large amount of data has been collected over the past 5 years, there remain gaps in the understanding of many aspects of the use of nusinersen in SMA beyond modest increases in peripheral muscle strength and in particular whether these improvements will translate into reduced respiratory morbidity and less respiratory failure with dependence upon non-invasive ventilation (NIV) (10).The paper by Lavie et al. (5) contributes to our understanding with its focus on ‘real-world’ variables including starting or ongoing need for assisted ventilation, the use of mechanical insufflation-exsufflation, respiratory complications, and treatment cessation due to respiratory reasons, or death in around 15% of cases attributed to pulmonary aspiration. In essence, it is a source of modest encouragement for clinicians as the majority of children demonstrated stability of respiratory support over the first two years of treatment with nusinersen which is in itself much better than the natural history of the condition with progressive decline and death in 90% by the age of 2 years. However, there are some gaps in knowledge in this paper which will require further studies. It is unclear exactly why children started ventilation specifically, who went to tracheostomy and why others went to NIV and what their initial ventilator pressures were. Management algorithms have been available to outline this in neuromuscular diseases . Further, it is unclear how many children had polysomnograms and what the results were in terms of apnoea indices, measures of hypoventilation, alterations in oxygenation and extent of transcutaneous CO2 abnormalities, other than that they were consistent with the standards of care for the treatment of children with SMA published in 2007 . Further guidelines have since emerged in the nusinersen era . Certainly, the positive impact of the use of NIV on respiratory outcomes, including hospitalisations, albeit in the broader neuromuscular population, has been established . As would be hoped, a reduction in admissions was seen in the present study in SMA1. Nonetheless, as all clinicians appreciate, what is prescribed and what is used for the treatment of anything in “the real world” varies widely. Think of asthma preventers or any therapies in cystic fibrosis including expensive correctors. In a prospective study on real world respiratory outcomes, the absence of information on adherence with average daily hours of support from memory cards inside the NIV devices is a short-coming of the study of Lavie et al. (5). This is something which, with serial assessment of polysomnography parameters, should be addressed in future studies in SMA1 treated patients to ascertain the true rather than potentially perceived benefit of NIV.Lavie et al. (5) provide insight into the everyday clinical respiratory burden of patients with SMA1 treated with nusinersen while highlighting further areas of research. Specifically, they rightly suggest a beneficial effect with the earliest initiation of nusinersen due to the possibility that nusinersen may have an effect on preserving respiratory function if started at a younger age. This mirrors data in the larger RCT where earlier treatment was associated with better motor outcomes. Logically, this could be readily achieved with emerging increase in new born screening programs including SMA genes in countries such as Australia and Belgium . This would also enable quantification of the number of copies of SMN2 genes present, missing in 30% of cases in the series of Lavie et al. (5). This stratification of genotype may be more important than ever in the nusinersen era as we improve our ability to predict outcomes beyond age of presentation [Types 1a, 1b and 1c] . The argument for newborn screening for SMA, with earlier diagnosis and improved outcomes for such an expensive therapy seems persuasive.This article explores patient outcomes in a real-world setting and found that the need for assisted ventilation did not worsen as would be with the natural progression of SMA1. However, they showed no improvement either. Therefore, nusinersen is a small step forward with the promise of much more to come from gene therapy and potentially combinations of therapies. Longer term studies with international prospective data registries are warranted and should be funded by international neuromuscular societies at arm’s length from pharmaceutical companies. It is as important to document respiratory outcomes rather than just predominantly modest motor outcomes not only for SMA1 but also SMA2 and SMA3, because at the end of the day in the real world, your respiratory wellbeing determines morbidity and mortality.References1. LoMauro A, Mastella C, Alberti K, Masson R, Aliverti A, Baranello G. Effect of nusinersen on respiratory muscle function in different subtypes of type 1 spinal muscular atrophy. American Journal of Respiratory and Critical Care Medicine. 2019;200(12):1547-1550.2. Kolb SJ, Coffey CS, Yankey JW, Krosschell K, Arnold WD, Rutkove SB, et al. Natural history of infantile-onset spinal muscular atrophy. Ann Neurol. 2017; 82(6):883-8913. Sugarman EA, Nagan N, Zhu H, Akmaev VR, Zhou Z, Rohlfs EM, et al. Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: Clinical laboratory analysis of >72 400 specimens. Eur J Hum Genet. 2012; 20 (1):27-324. Farrar MA, Park SB, Vucic S, Carey KA, Turner BJ, Gillingwater TH, et al. Emerging therapies and challenges in spinal muscular atrophy. Annals of Neurology. 2017; 81(3):355-3685. Lavie M, Diamant N, Cahal M, Sadot E, Be’er M, Fatal A, Sagi L, Domany KA, Amirav I. Nusinersen for Spinal muscular Atrophy Type 1: real World Respiratory Experience. Pediatr Pulmonol 2020; XXXX; doi xxxx6. Finkel RS, Mercuri E, Darras BT, Connolly AM, Kuntz NL, Kirschner J, et al. Nusinersen versus sham control in infantile-onset spinal muscular atrophy. N Engl J Med. 2017; 377:1723-17327. LoMauro A, Mastella C, Alberti K, Masson R, Aliverti A, Baranello G. Effect of nusinersen on respiratory muscle function in different subtypes of type 1 spinal muscular atrophy. American Journal of Respiratory and Critical Care Medicine. 2019 Dec 15;200(12):1547-508. Sansone VA, Pirola A, Albamonte E, Pane M, Lizio A, et al Respiratory Needs in Patients with Type 1 Spinal Muscular Atrophy Treated with Nusinersen. The Journal of Pediatrics. 2020; 219 P223-228. E49. K-A. Chen, J. Widger, A. Teng, D.A. Fitzgerald, A. D’Silva, M. Farrar, Real-world respiratory and bulbar comorbidities of SMA type 1 children treated with nusinersen: 2-year single centre Australian experience, Paediatric Respiratory Reviews (2020), doi: httpds://doi.org/10.1016/j.prrv.2020.09.00210. Fitzgerald DA, Doumit M, Abel F. Changing respiratory expectations with the new disease trajectory of nusinersen treated spinal muscular atrophy [SMA] type 1. Paediatric Respiratory Reviews. 2018 Sep 1;2 8:11-7.11. Hull J, Aniapravan R, Chan E, Chatwin M, Forton J, Gallagher J, Gibson N, Gordon J, Hughes I, McCulloch R, Russell RR. British Thoracic Society guideline for respiratory management of children with neuromuscular weakness. Thorax. 2012 Jul 1;67(Suppl 1):i1-40.12. Wang CH, Finkel RS, Bertini ES, Schroth M, Simonds A, Wong B, Aloysius A, Morrison L, Main M, Crawford TO, Trela A. Consensus statement for standard of care in spinal muscular atrophy. Journal of child neurology. 2007 Aug;22(8):1027-49.13. Finkel RS, Mercuri E, Meyer OH, Simonds AK, Schroth MK, Graham RJ, Kirschner J, Iannaccone ST, Crawford TO, Woods S, Muntoni F. Diagnosis and management of spinal muscular atrophy: Part 2: Pulmonary and acute care; medications, supplements and immunizations; other organ systems; and ethics. Neuromuscular Disorders. 2018 Mar 1;28(3):197-207.14. Young HK, Lowe A, Fitzgerald DA, Seton C, Waters KA, Kenny E, Hynan LS, Iannaccone ST, North KN, Ryan MM. Outcome of noninvasive ventilation in children with neuromuscular disease. Neurology. 2007 Jan 16;68(3):198-201.15. Boemer F, Caberg JH, Dideberg V, Dardenne D, Bours V, Hiligsmann M, Dangouloff T, Servais L. Newborn screening for SMA in Southern Belgium. Neuromuscular Disorders. 2019 May 1;29(5):343-9.
An Unusual Case of Necrotizing Pneumonia Presenting with Acute Kidney InjuryUgur Berkay Balkanci, MDSchool of Public Health, University of Minnesota, Minneapolis, MNDavid J. Sas, DODivision of Pediatric Nephrology and Hypertension, Department of Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, MinnesotaNadir Demirel, MDDivision of Pediatric Pulmonology, Department of Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, MinnesotaCorresponding Author:Nadir Demirel, MDDivision of Pediatric Pulmonology200 First Street SWRochester, MN 55906Tel. No.: 5075380754Fax No.: 5072840727Demirel.email@example.comKey words: postinfectious glomerulonephritis, pneumothorax, complications, complicated pneumoniaFinancial Disclosure: The authors have indicated they have no financial relationships relevant to this article to disclose.Funding: No external funding.Short title: “An unusual case of necrotizing pneumonia”To the Editor:Lower respiratory tract infections are the most common reason for hospitalization in the pediatric age group in the United States. Although pneumonia is prevalent, complicated pneumonia such as empyema, lung abscess and necrotizing pneumonia (NP) is uncommon in children1. The prevalence of complicated pneumococcal pneumonia decreased significantly after the introduction of the thirteen-valent pneumococcal vaccine in 20101. NP in the pediatric population is a severe disease characterized by extensive destruction and liquefaction of the lung tissue resulting in loss of the pulmonary parenchymal architecture, cavitation of the lung, and pleural involvement. Renal complications of complicated pneumonia are rare and mostly reported as atypical hemolytic uremic syndrome (HUS)2. Post-infectious glomerulonephritis (PIGN) is an unexpected complication of bacterial pneumonia3.We report a six-year-old otherwise healthy fully vaccinated girl with a 4-day history of fever, abdominal pain, vomiting, non-bloody diarrhea, and poor oral intake. Parents reported decreased urine output and dark-colored urine on the day of admission. Initial evaluation revealed serum creatinine of 5.01 mg/dL and blood urea nitrogen of 86 mg/dL, elevated acute phase reactants suggesting acute kidney injury (AKI) in the setting of an undiagnosed acute infectious process. The patient was admitted with decreased effective circulatory volume. Urinalysis revealed hematuria with <25% dysmorphic red blood cells (RBCs), proteinuria, pyuria, and RBC casts and granular casts, suggestive of acute glomerulonephritis.She was started on intermittent hemodialysis at day 2 of admission to address uremia, fluid overload, and hyperphosphatemia. A renal biopsy revealed diffuse exudative glomerulonephritis, consistent with infection-related glomerulonephritis. ASO, Anti-DNase B were negative; C3, C4 levels were low. She was treated with pulse IV methylprednisolone 10mg/kg/day for three days. The first 5 days in the hospital, the patient remained afebrile and her lung exam was normal without respiratory symptoms.On day six of admission, she developed acute right-sided chest pain and shortness of breath during hemodialysis. Chest x-ray (CXR) revealed a large right-sided tension pneumothorax, prompting therapeutic chest tube placement. Repeat CXR revealed reexpansion of the right lung and a significant right upper lobe consolidation with an ovoid hyperlucency and an air-fluid level. A chest CT scan confirmed the diagnosis of NP with multiple cavities (Image).Flexible bronchoscopy was performed with bronchoalveolar lavage revealing 42% neutrophils and negative cultures. She was treated with broad spectrum intravenous antibiotics.During admission, she developed hypertension, well-controlled with scheduled enalapril and amlodipine, as well as isradipine as needed. On day 14 of admission, hemodialysis was discontinued as kidney function improved, and chest tube was removed. She was discharged at day 26 of admission on intravenous ceftriaxone and oral metronidazole to complete 30 days of treatment. A repeat chest CT at end of treatment showed complete resolution of NP. Renal functions and blood pressure normalized on follow up.NP is characterized by persistent high fevers and prolonged hospitalizations even with appropriate antibiotic treatment1. Most often, NP affects immunocompetent children with no underlying risk factors4. The pathophysiology of this complication is acute liquefactive necrosis of the lung parenchyma which results in the development of pneumatoceles4. The most common pathogen causing NP is Streptococcus pneumoniae followed by Staphylococcus aureus and Streptococcus pyogenes. Other rarer bacterial and viral pathogens are Mycoplasma pneumonia, Influenza, and Adenovirus1. Identifying the microbiologic pathogen can be challenging and is only made in 50% of cases1. In our case, we did not isolate the causative microorganism. NP typically resolves without residual morbidity, even after a protracted course1,4.Pleural involvement is almost universal in NP, and the course of pleural disease often determines duration and outcome, particularly as it relates to the complication of bronchopleural fistula (BPF)1. BPF is most likely due to the necrotic development of a connection between bronchial space and pleural space4. BPF formation is associated with a significantly longer hospital stay in children with NP4. Yet, most cases heal without surgical intervention4. Tension pneumothorax has been observed as a rare complication of NP1.Renal involvement in complicated pneumonia is rare. Atypical HUS has been reported as a complication of pneumonia, particularly associated with empyema. (most commonly due to invasive Streptococcus pneumoniae)2. In a case series of 37 cases of atypical HUS, 34 patients (92%) had pneumonia with 10 patients (29%) with NP5. Less commonly, pneumonia can be associated with PIGN. PIGN is the most common glomerulonephritis in children worldwide. Pneumonia-associated PIGN is rare. In a case series from the US, PIGN accounted for 0.15% of admissions for pneumonia and 0.39% of admissions for glomerulonephritis6. Pneumonia-associated PIGN is known to be caused by various bacterial pathogens including Streptococcus pneumoniae, Staphylococcus aureus, Mycoplasma pneumoniae, Chlamydia pneumoniae, Nocardia, and Coxiella burnetii3. Different from the usual presentation of the PIGN (in which the time interval between a pharyngeal group A Streptococcal infection and PIGN is 6 to 10 days), pneumonia-associated PIGN is usually concomitant with the pulmonary disease3,6.Our case is unusual in several ways: pneumonia-associated PIGN typically presents with respiratory symptoms first, and acute kidney injury developing during the course of pneumonia3. More surprisingly, the patient developed NP which is characterized by even more severe respiratory symptoms1. Yet, our patient presented without respiratory complaints and pneumonia became apparent only after the development of pneumothorax. We could only identify 2 cases of pneumonia-associated PIGN who presented with renal involvement before pulmonary complaints6,7. Also, previous cases in the literature of pneumonia-associated PIGN report mostly a non-complicated course of pulmonary disease3,6. In a case series of 11 children with pneumonia-associated PIGN, only one case developed a small empyema6. Similarly, the majority of the reported cases of pneumonia-associated PIGN describe a benign course of renal disease3,6. Our patient’s kidney failure progressed rapidly, and she required 2 weeks of intermittent hemodialysis and a three-day course of pulse steroid therapy. At present, systemic corticosteroids are not recommended for patients with complicated pneumonia. A Cochrane review including 17 randomized controlled trials, of which four were conducted on children, found that corticosteroid therapy reduced mortality and morbidity in adults with severe CAP, and morbidity, but not mortality, in adults and children with non-severe CAP1. We speculate that pulse steroid treatment may have modified the course of NP in our patient.This case suggests an atypical presentation of NP with predominant renal complications is possible. Pediatricians should be aware of renal complications of respiratory diseases. Systemic steroids should be considered in the treatment of NP.References:1. de Benedictis FM, Kerem E, Chang AB, Colin AA, Zar HJ, Bush A. Complicated pneumonia in children. Lancet 2020;396:786-798.2. Spinale JM, Ruebner RL, Kaplan BS, Copelovitch L. Update on Streptococcus pneumoniae associated hemolytic uremic syndrome. Curr Opin Pediatr 2013;25:203-208.3. Carceller Lechón F, de la Torre Espí M, Porto Abal R, Écija Peiró JL. Acute glomerulonephritis associated with pneumonia: a review of three cases. Pediatr Nephrol 2010;25:161-164.4. Sawicki GS, Lu FL, Valim C, Cleveland RH, Colin AA. Necrotising pneumonia is an increasingly detected complication of pneumonia in children. Eur Respir J 2008;31:1285-1291.5. Banerjee R, Hersh AL, Newland J, Beekmann SE, Polgreen PM, Bender J, Shaw J, Copelovitch L, Kaplan BS, Shah SS. Streptococcus pneumoniae-associated Hemolytic Uremic Syndrome Among Children in North America. Pediatr Infect Dis J 2011;30:736-739.6. Srivastava T, Warady BA, Alon US. Pneumonia-associated acute glomerulonephritis. Clin Nephrol 2002;57:175-182.7. Schachter J, Pomeranz A, Berger I, Wolach B. Acute glomerulonephritis secondary to lobar pneumonia. Int J Pediatr Nephrol 1987;8:211-214.
Neuromuscular medicine is being revolutionized by new genetic and molecular therapies. The purpose of this Special Issue is to present an overview of these new therapies, to examine their cardiopulmonary effects, and to consider the future of neuromuscular cardiopulmonary care. The emphasis will be on Duchenne muscular dystrophy (DMD) and, to a lesser extent, spinal muscular atrophy (SMA), as these are the diseases with the most robust new drug development and related cardiopulmonary outcome data. This Special Issue contains articles on a number of relevant topics, including an overview of new genetic and molecular therapies for DMD, examining the currently available cardiopulmonary outcome data; and a critical examination of pulmonary outcome measures, assessing which outcomes should be used in treatment studies. We will provide an overview of cardiopulmonary phenotypic variability and discordance and their implications for assessing patient prognosis and response to therapies, and present a new perspective on neuromuscular-induced sleep-disordered breathing, viewed in the context of new and emerging therapies. Finally, we will consider which cardiac imaging modalities should be used as outcome measures in studies assessing DMD heart function, and take a look at novel therapeutic approaches to DMD heart disease, including management of rhythm disorders and heart failure, and the use of left ventricular assist devices.
Editorial: Natural Sciences is debuting“There’s a way to do it better – find it.” –Thomas A. EdisonWelcome to Wiley’s new flagship journal, Natural Sciences. Our aim is to meet the challenge of publishing top-tier papers in an open-science environment and thereby contribute to innovating the ways scientists communicate with one another and with society at large. We encourage you to partake in this transformative endeavor.Natural Sciences is an inter- and multidisciplinary journal that publishes outstanding research from the global community spanning biology, chemistry, and physics and their interfaces, as well as seminal works from related fields such as engineering and biomedical research. The journal’s aspiration is to promote the sharing and hybridization of disciplinary perspectives and thereby to foster crossing of the traditional boundaries that have previously separated disciplines. The journal will feature Research Articles of all lengths and formats, Commentaries, and Reviews, as well as Editorials, Highlights, Book Reviews, and News items.In contrast to many other high-ranking “elite” journals, Natural Sciences is run by practicing academic scientists who will treat submitted papers just like they wish their own papers would be treated – fairly, quickly, and without bias. That’s why our tagline readsA Journal of, by, and for scientists .By embracing open science, Natural Sciences will promote the global scientific community’s shared goal of enriching society with freely accessible prime scientific research. With open-science in general and open-access publishing in particular, the cost of scientific publishing will be carried by funding agencies or research institutions, and not the reader. Subscription-model-based academic publishing will be relegated to the sidelines, and scientific publications made freely accessible and re-usable for all.Moreover, Natural Sciences supports the cultural changes in the research community that call for increased transparency and openness in communicating and sharing the results of scientific research. Open science encompasses not only open-access publishing but also open peer review and sharing of primary scientific data. These, along with reviewer recognition, are key innovations effecting such a transformation and will be espoused by Natural Sciences .In developing the concept of Natural Sciences , we worked closely with Wiley to ensure efficient editorial practices. Wiley’s international network of experienced professionals steeped in scientific publishing are there for us 24/7. Together, we are committed to open-science publishing that is timely and rigorous – and to embracing open-science innovations in the process.The ideas and values that led us to envision Natural Sciences are summarized in our Manifesto [link to https://onlinelibrary.wiley.com/page/journal/26986248/homepage/manifesto].Natural Sciences is now open for submissions [link to https://mc.manuscriptcentral.com/naturalsciences]. The Article Processing Charge (APC) will be waived during the first two years.Looking forward to your submissions,Bretislav Friedrich, Executive EditorMarianne Bronner, Chief Biology EditorVivian Yam, Chief Chemistry EditorGerard Meijer, Chief Physics Editor [link all the names to https://onlinelibrary.wiley.com/page/journal/26986248/homepage/editorial-board]
This study presents a rare case of postoperative amyloidosis of the tongue base and provides a summary of the known literature of tongue amyloidosis. The diagnosis was by physical examination, radiological findings, and histopathological Congo red stain. Bone marrow biopsy the revealed “Plasma cell myeloma” as a cause.
The sinoatrial node in medication-resistant inappropriate sinus tachycardia: to modify or to ablate?Khalil El Gharib1*1Hôtel-Dieu de France, Beirut, Lebanon*Author for correspondence: firstname.lastname@example.orgKEYWORDS: IST, sinus node modification, sinus node ablation, radiofrequency ablation, surgical ablationNo conflict of interest to discloseFunding: noneInappropriate sinus tachycardia (IST) is defined as a resting heart rate >100 beats per minute (with a mean heart rate >90 beats per minute over 24 hours) associated with highly symptomatic palpitations(1). The syndrome is associated neither with structural heart disease nor with any secondary cause of sinus tachycardia(2) and evidence suggests that enhanced intrinsic automaticity of the sinoatrial node, which can be due to anti-β-adrenergic antibodies, is behind its genesis(3). However, it is benign in terms of clinical outcomes and echocardiographic evidence of ventricular dysfunction(4), being rarely associated with tachycardia-induced cardiomyopathy(3).Patients with IST are essentially treated with ß-blockers to alleviate their symptoms(5). Ivabradine, a drug that inhibits funny calcium channels, particularly abundant in the SA node, showed modest benefit, receiving class IIa recommendation in the treatment of IST(4). But, the duration of medical therapy might be indefinite, and, a considerable number of patients would respond inadequately, or have no response, even after prolonged therapy(5). Historically, such patients would have subtotal right atrial excision, atrioventricular junctional ablation with permanent pacemaker implantation, or chemical occlusion of the sinus node artery(6). These options are considered today unacceptable in this setting, and other therapeutic approaches should be unveiled when resistance to medical treatment appears.Electrophysiological study was initially purely diagnostic, but recent advances in technology have allowed us to intervene(7); patients with ventricular and supraventricular tachyarrhythmias are successfully treated with percutaneous catheter procedures. Of these, SA node ablation/ modification has been proposed as alternative approaches in IST that is not responding to medical treatment; trials reported auspicious results, highlighted here.Electrophysiologic mapping to the site of the earliest endocardial activation during either spontaneous sinus tachycardia or isoproterenol-induced sinus tachycardia has rendered these procedures feasible(8). Additionally, combination with intracardiac echocardiography permitted a more accurate electrophysiologic and anatomic localization of the sinoatrial node(9).Sinus node modification is not a focal ablation, but requires complete abolition of the cranial portion of the SA node complex, the one that exhibits the most of the autonomic activity(9). It is defined as successful when the heart rate decreases by 30 beats per minute (bpm) during isoproterenol infusion(8). Short-term success was also defined by other investigators when there was a reduction of the baseline sinus rate to less than 90 bpm and the sinus rate during isoproterenol infusion by more than 20% or by 25%(8). The acute success rate for modification has been varying between 76 and 100 % across trials, while long-term clinical outcomes are modest at best, with reported freedom from IST ranging from 23 to 85%(10).Complications specific to SA node modification include superior vena cava (SVC) syndrome, diaphragmatic paralysis, and sinus node dysfunction(10). And while modification with conventional methods has its setbacks, modification using laser energy can be considered in the setting of IST. This modality creates clear-cut homogenous transmural lesions of the myocardium that comprises the scattered “functional” SA node(11). The burnt myocardium will then heal into a dense fibrous scar, decreasing potential amplitudes. And when adapting laser energy settings to the thickness of the myocardial wall, collateral damages such as esophageal fistulae, lung burns, and phrenic nerve palsy will be avoided(11); thus, this technique may prove itself as a new intriguing alternative for the safe and effective treatment of IST.SA node modification is apt in achieving acute reductions in postprocedural heart rate. However, and as aforementioned, success rates are suboptimal in terms of symptomatic control with a significant recurrence rate(12). Catheter ablation aiming at either total exclusion and obliteration of the SA node has been described and performed, success being defined as a slowing of >50% from the baseline rate of tachycardia along with a junctional escape rhythm(12). With radiofrequency (RF) applications, the earliest local atrial activation time would shift from a cranial location to a more caudal one, usually at the mid-lateral right atrium(5). Reviews have reported that acute success rates were consistently to be as high as 88.9%, with an overall frequency of recurrence of 19.6%, the latter occurring within a wide range of post-ablation intervals, anywhere from a few weeks to several months after the procedure(12). Additionally, Takemoto and colleagues documented a significant drop in B-type natriuretic peptide levels, 6 to 12 months after ablation, suggesting fewer stretching shears on cardiac muscle.Two types of response of the sinus tachycardia to RFA were observed across studies, whether a step-wise reduction in sinus rate accompanying migration of the site of earliest atrial activation in a cranial-caudal direction along the lateral right atrial wall, or an abrupt drop in heart rate in response to RFA at a focal site of earliest atrial activation(13).However, RFA of inappropriate sinus tachycardia requires a large number of applications of radiofrequency energy and is, as in SA node modification, associated with a high recurrence rate(13). Complete remission is achieved only in approximately 50% of patients in some studies(14); longer history of IST and those reporting near syncope/syncope having a higher probability of recurrence(15).While other studies have shown that RF ablation of the SA node can achieve even longer-term reductions in the sinus rate and relief of symptoms in two-thirds of patients with drug-refractory, inappropriate sinus tachycardia(13), aiming specific sites related to the SA node should be elaborated, for better and optimal outcomes Killu and colleagues created a lesion in the arcuate ridge resulting in complete abolition of the tachycardia, since arrhythmias arising in this region may exhibit both electrocardiographic and clinical similarities to IST(16). This has led to consider ablation of the arcuate ridge as a treatment of refractory IST, necessitating larger trials to confirm its potential role.Phrenic nerve injury is a severe and dreaded complication of SN ablation(12). Pericarditis, right diaphragmatic paralysis, and SVC syndrome are other undesirable side effects of the procedures, variously reported in studies. but a common complication was observed in them all, atrial tachyarrhythmias(12). It has been hypothesized that myocardial pathology, such as inflammation and fibrosis, considered iatrogenic due to the ablation procedures, may be promoting arrhythmias both in the region of the SA node, as well as in remote locations(12). Through multivariable analysis, higher resting heart rates post-ablation and smaller cranial-to-caudal shifts have been defined as predictors of atrial arrhythmias(15). In conclusion, catheter ablation could be considered an effective treatment for highly symptomatic, drug-refractory patients, even for those who did not respond to SA node modification(5).The sinus node is located close to the epicardial surface and catheter-based ablations do not always make full-thickness lesions across the atrial muscle, leading to failure of the ablation(17), besides the numerous trabeculae and the widely variable anatomy.Surgical ablation is not a first-line or routine management strategy for IST, but it has been proposed when IST resists or recurs after SN modification/ endocardial ablation(17). Effectively, in several studies, epicardial lesions, through a single small incision in one of the intercostal spaces, successfully slowed heart rate and shifted activation to a more caudal location, and surprisingly, subsequent endocardial lesions led to an even greater drop in heart rate and more caudal site of earliest activation(18). These outcomes were again replicated when using minimally invasive thoracoscopic ablation of the epicardial site of the SA node, concluding of the promising efficacy and the safety of this approach, since it preserves the phrenic nerve(17), although continued follow-up after surgery is required.Medication-resistant IST remains a medical challenge for physicians and cardiologists; and in the era of great advances in interventional cardiology, its treatment remains debatable. Sinus node modification/ ablation is not recommended as first-line therapy in IST, this procedure should be considered only in drug-refractory patients who have severe symptoms(13). Although the number of patients in the available studies is generally small, both procedures have documented an encouraging success rate in the short-term, while being less impressive in the long-term. It has been hypothesized that this discrepancy is due to the relatively large potential area of atrial pacemaker cells(18); modification or ablation may fail to ablate or isolate all the pathways that comprise the functional SA node because they often target the anatomic part and the area of earliest atrial activation(19). Others have explained that the long-term slowing in rhythm fails because these procedures inconsistently produce transmural lesions in the right atrium. Surgical treatment of IST has proposed a solution to the latter conflict when isolating the SA node with a wide cuff of surrounding atrial muscle(19). And with the advent of bipolar RF clamps and minimally invasive cardiac surgical techniques with thoracoscopic guidance, this approach appears more appealing than before, especially when combined with endocardial ablation(19). But again, current data specifies employing these techniques in highly selected cases.
Comment on: The use of anakinra in the treatment of secondary hemophagocytic lymphohistiocytosis1Paige Vicenzi, OMS-IV, 2Zahra Jiwani, DO, 3Ricardo Guirola, MD,1,4Tyler Hamby, PhD, 5Anish Ray, MD1Texas College of Osteopathic Medicine, University of North Texas Health Science Center2Department of Pediatrics, Children’s Hospital of Michigan3Department of Pediatric Rheumatology, Cook Children’s Health Care System4Department of Research Operations, Cook Children’s Health Care System5Department of Pediatric Hematology/Oncology, Cook Children’s Health Care SystemCorresponding Author:Anish Ray, MD1500 Cooper St., 5th floor,Fort Worth, TX 76104Phone: 425-205-0926Anish.Ray@CookChildrens.orgWord Count: 497Number of Tables: 0Number of Figures: 1Running Title: Anakinra in Secondary HLHKeywords: hemophagocytic lymphohistiocytosis, anakinra, pediatricThe authors have no financial support or conflicts of interest.Hemophagocytic lymphohistiocytosis (HLH) is a rare yet potentially fatal systemic disease arising from uncontrolled activation of the immune system. According to the Histiocyte Society’s 2004 guidelines, patients must meet five of eight criteria to be diagnosed with HLH . HLH may be classified into primary and secondary. Primary, or familial, HLH is attributed to underlying defects in genes that control natural killer (NK) and cytotoxic T-lymphocyte (CTL) cell degranulation. Secondary HLH, in contrast, may occur in the context of triggers, such as malignancy, rheumatologic disease, or infection. Systemic-onset juvenile idiopathic arthritis (SoJIA) is a well-recognized trigger of HLH and both share overlapping features (e.g. fever and elevated ferritin). Management of SoJIA includes the immunomodulator Anakinra, an interleukin 1 (IL-1) receptor antagonist hypothesized to dampen an overactive immune system. Three patients treated for HLH with concomitant SoJIA diagnosis at Cook Children’s Medical Center between 2014 and 2019 are described below in order to examine the role of immunomodulators in their clinical course and outcome.Three Hispanic patients (aged 8-15) presented with a constellation of systemic symptoms, including fever, generalized rash, fatigue, and weight loss. Upon fulfilment of necessary criteria and subsequent diagnosis of HLH, they were treated accordingly with HLH-2004 protocol. Case 3, whose HLH was suspected to be secondary to Epstein-Barr Virus (EBV) infection, rapidly responded to treatment and, therefore, briefly discontinued Etoposide; however, she tolerated this poorly and resumed treatment after a six-week hiatus with the addition of weekly Rituximab to mitigate rising EBV titers. All patients achieved remission.Past medical history for case 3 included autoimmune disorders such as celiac disease, type 1 diabetes and suspected idiopathic juvenile arthritis for which she did not require ongoing care prior to presenting with features of secondary HLH. Cases 1 and 2 were diagnosed with SoJIA following their HLH diagnosis. Cases 1 and 3 relapsed with HLH within months of their initial encounter. Due to their concurrent diagnosis of SoJIA, both received daily Anakinra. Case 3 experienced rapid resolution of symptoms. In contrast, Case 1 had unsatisfactory response of musculoskeletal manifestations prompting switch from Anakinra to weekly Tocilizumab—another biologic that antagonizes IL-6 receptor—with favorable response. Case 2 was started on daily Anakinra immediately following his diagnosis of SoJIA and has yet to relapse. In summary, all cases have yet to experience an additional relapse following introduction of Anakinra or Tocilizumab. Figure 1 provides the treatment timelines for Cases 1-3 who had 5.37, 2.87, and 4.62 years of follow up, respectively.Though traditional therapy for HLH includes intensive courses of etoposide and corticosteroids with substantial risk for morbidity and mortality, biologics represent a newer class of medications highly effective in treating diseases with inflammatory or immune-mediated components . In a reimaging of the HLH treatment algorithm, a recent study proposes Anakinra as initial treatment with sequential escalation of immunosuppression to mitigate adverse effects . This case series reinforces that immunomodulators, such as Anakinra, are safe and promising treatment options in pediatric patients with secondary HLH.
Carotenoids are widely used in functional foods, cosmetics, and health supplements, and their importance and scope of use are continuously expanding. Here, we characterised carotenoid biosynthetic genes of the plant-pathogenic bacterium Pantoea ananatis, which carries a carotenoid biosynthetic gene cluster (including crtE, X, Y, I, B, and Z) on a plasmid. Reverse transcription–polymerase chain reaction (RT-PCR) analysis revealed that the crtEXYIB gene cluster is transcribed as a single transcript and crtZ is independently transcribed in the opposite direction. Using splicing by overlap extension with polymerase chain reaction (SOE by PCR) based on asymmetric amplification, we reassembled crtE–B, crtE–B–I, and crtE–B–I–Y. High-performance liquid chromatography confirmed that Escherichia coli expressing the reassembled crtE–B, crtE–B–I, and crtE–B–I–Y operons produced phytoene, lycopene, and β-carotene, respectively. We found that the carotenoids conferred tolerance to UV radiation and toxoflavin. Pantoea ananatis shares rice environments with the toxoflavin producer Burkholderia glumae and is considered to be the first reported example of producing and using carotenoids to withstand toxoflavin. We confirmed that the carotenoid production of P. ananatis is dependent on RpoS, which is positively regulated by Hfq/ArcZ and negatively regulated by ClpP, similar to an important regulatory network of E. coli (HfqArcZ → RpoS Ͱ ClpXP). We also demonstrated that Hfq-controlled quorum signalling de-represses EanR to activate RpoS, thereby initiating carotenoid production. Survival genes such as those responsible for the production of carotenoids of the plant-pathogenic P. ananatis must be expressed in a timely manner to overcome stressful environments and compete with other microorganisms. This mechanism is likely maintained by a brake with excellent performance, such as EanR.
Xiaodong Zhang1, MD, PhD, Ruike Yang1 2, MD, Luigi Di Biase1, MD, PhD, FHRS1 Division of Cardiology, Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York2 Division of Cardiology, Department of Medicine, Henan Provincial People’s Hospital, Zhengzhou, ChinaCorrespondence : Dr Luigi Di Biase, Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210th St, Bronx, NY 10467. E-mail address: email@example.com .Keywords : narrow complex tachycardia, dual atrioventricular nodal non-re-entrant tachycardia, dual atrioventricular nodal re-entrant tachycardia, autonomic nervous system
Background: Antiepileptic drugs (AEDs) are widely used for the treatment of epilepsy, but they can be associated with the development of mainly delayed/non-immediate hypersensitivity reactions (HRs). Although these reactions are usually cutaneous, self-limited and spontaneously resolve within days after drug discontinuation, sometime HRs reactions to AEDs can be severe and life threatening. Aim: This paper seeks to show examples on practical management of AEDs HRs in children starting from a review of what it is already known in literature. Results: Risk factors include age, history of previous AEDs reactions, viral infections, concomitant medications and genetic factors. The diagnosis work-up consists of in vivo (Intradermal testing and Patch testing) and in vitro tests [serological investigation to exclude the role of viral infection, lymphocyte transformation test (LTT), cytokine detection in ELISpot assays and granulysin (Grl) in flow cytometry]. Treatment is based on a prompt drug discontinuation and mainly on the use of glucocorticoids. Conclusion: Dealing with AEDs HRs is challenging. The primary goal in the diagnosis and management of HRs to AEDs should be trying to accurately identify the causal trigger and simultaneously identify a safe and effective alternate anticonvulsant. There is therefore an ongoing need to improve our knowledge of HS reactions due to AED medications and in particular to improve our diagnostic capabilities.
When Thetis dipped her son Achilles into the River Styx to make him immortal, she held him by the Heel, which was not submerged, and thus created a weak spot that proved deadly for Achilles. Millennia later, Achilles Heel is part of today’s lexicon meaning an area of weakness or a vulnerable spot that causes failure. Also implied is that an Achilles Heel is often missed, forgotten or underappreciated, until it is under attack, and then failure is fatal. Paris killed Achilles with an arrow ‘guided by the Gods’. At the International Congress of the Immunology of Diabetes Society, 2018, five leading experts were asked to present the case for a particular cell/element that could represent the Achilles Heel of T1D. Their arguments are summarized here, to make this case.
Aim: To show if lower urinary tract symptoms (LUTS) could be symptoms of COVID-19 with validated questionnaires. Methods: The 96 COVID-19 patients who were hospitalized at a tertiary center were collected retrospectively. After the exclusion criteria, 46 patients were consisted as the study population. The male and female patients then fill formed the International Prostate Symptom Score and Urinary Symptom Profile respectively. All patients responded to these questions for the three period. Results: 27 female (58.6 %) and 19 male (41.4 %) COVID-19 patients answered the questions In the male patients, while there were no statistically significant differences in the total IPSS, the voiding IPSS score, and quality of life between the three periods (p=0.148; p=0.933, p=0.079, respectively), the storage IPSS scores had a significant difference between the three periods (p=0.05). In the female patients, low stream scores, were similar between the three periods (p=0.368). The scores of stress incontinence and an overactive bladder had a significant difference between the three periods (p=0.05 and p=0.05). Conclusion: LUTS, especially storage symptoms, might be one of the initial symptoms of COVID-19 and the clinicians should evaluate LUTS with other known symptoms of the virus when a patient is suspected of having COVID-19.