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Yi Li

and 19 more

Aims: To optimize the dosing regimen in patients with severe renal impairment based on population pharmacokinetic/pharmacodynamic (PPK/PD) analysis. Methods: The pharmacokinetics and safety of nemonoxacin was evaluated in a single-dose, open-label, nonrandomized, parallel-group study after single oral dose of 0.5 g nemonoxacin capsule in 10 patients with severe renal impairment and 10 healthy controls. Both blood and urine samples were collected within 48 hours after admission and determined the concentrations. A PPK model was built using nonlinear mixed effects modelling. The probability of target attainment (PTA) and the cumulative fraction of response (CFR) against S. Pneumoniae and S. aureus was calculated by Monte Carlo simulation. Results: The data best fitted to a two-compartment model, from which the PPK parameters were estimated, including clearance (8.55 L/h), central compartment volume (80.8 L), and peripheral compartment volume (50.6 L). The accumulative urinary excretion was 23.4±6.5% in severe renal impairment patients and 66.1±16.8% in healthy controls. PPK/PD modeling and simulation of 4 dosage regimens found that nemonoxacin 0.5 g q48h was the optimal dosing regimen in severe renal impairment patients, evidenced by higher PTA (92.7%) and CFR (>99%) at nemonoxacin MIC ≤ 1 mg/L against S. pneumoniae and S. aureus. The alternative regimens (0.25 g q24h; loading dose 0.5 g on Day 1 followed by 0.25 g q24h) were insufficient to cover the pathogens even if MIC ≤ 0.5 mg/L. Conclusion: An extended dosing interval (0.5 g q48h) may be appropriate for optimal efficacy of nemonoxacin in case of severe renal impairment.

Hyung Kyu Park

and 7 more

Background: Air pollution can be a risk factor for respiratory viral transmission and infection. The COVID-19 outbreak in 2020 may have affected ambient air pollution levels. Therefore, this study aimed to investigate air pollution levels and respiratory virus infection rates before and after the COVID-19 pandemic as well as determine relationships between these factors. Methods: The daily mean temperature and concentrations of air pollutants (PM2.5, PM10, O3, NO2, CO, and SO2) in five metropolitan cities in South Korea were collected for the months of February to May from 2015 to 2020. Results of 14 respiratory viruses isolated using polymerase chain reaction in children with upper or lower respiratory tract infections were gathered during the same period. Trends of respiratory virus infection, temperature, and air pollutant level from February to May for six years were evaluated and possible relationships between respiratory virus infections and ambient air pollutant levels were assessed. Results: Most air pollutants exhibited significantly decreasing trends in 2020 compared to the years before COVID-19. There were no differences in temperature. Adenovirus, bocavirus, metapneumovirus, parainfluenza virus 3, and rhinovirus were the most frequently detected viruses from February to May from 2015 to 2019, and infection rates dropped significantly in 2020. The concentration of ambient O3 was associated with rhinovirus infection in hospitalized children (aOR [95% CI], 1.028 [1.002, 1.055]). Conclusions: After the COVID-19 outbreak, ambient air pollution levels and respiratory virus transmission decreased in the pediatric population of South Korea.
Objective: To calculate maternal mortality ratio (MMR) for 2006-2018 in the Netherlands and compare with 1993-2005. Describe women’s and obstetric characteristics, causes of death and improvable factors. Design: Prospective cohort study. Setting: Nationwide. Population: 2,304,271 livebirths. Methods: Analysis of all maternal deaths between January 1st, 2006, and December, 31st, 2018 as reported to and audited by the national Audit Committee Maternal Mortality and Morbidity. Main outcome measures: MMR, causes of death, improvable factors. Results: Overall MMR was 6.2 per 100,000 livebirths, a decrease from 12.1 in 1993-2005 (Odds Ratio (OR) 0.5, 95%CI 0.4-0.6). Women with non-Western ethnic background had a slightly increased MMR compared to Dutch women (MMR 6.5 vs 5.0, OR 1.3, 95%CI 0.9-1.9), and was particularly increased among women with a background from Surinam/Dutch Antilles (MMR 14.7 OR 2.9, 95%CI 1.6 – 5.3). Half of all women had an uncomplicated medical history (79/161, 49.1%). Of 172 pregnancy-related deaths within one year postpartum, 103 (60%) had a direct and 69 (40%) an indirect cause. Leading causes within 42 days postpartum were cardiac disease (n=21, 14.8%), hypertensive disorders (n=20, 14.1%) and thrombosis (n=19, 13.4%). For deaths up to one year postpartum, suicide was the third commonest cause (n=20, 11.6%). Improvable factors in care were identified in 76 (47.5%) of all deaths. Conclusions: Maternal mortality halved in 2006-2018 compared to 1993-2005. Unlike before, cardiac disease outnumbered hypertensive disorders as main cause of death. Women with a background from Surinam/Dutch Antilles had a threefold higher risk of death compared to Dutch women.

Haijiang Liu

and 11 more

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Oktay Ucer

and 3 more

Semih Ak

and 1 more

Background: Hookah is a tobacco product of Middle Eastern origin; however, its popularity increases in Europe and the US. Despite its frequent use, hookah’s potentially detrimental effects are underestimated due to the scarcity of the relevant research. Since septoplasty is one of the most commonly performed procedures of otolaryngology practice, we aimed to investigate the impact of hookah consumption on recovery after septoplasty. Methods: Patients who underwent septoplasty in Sanliurfa Training and Research Hospital Department of Otolaryngology between January 2017 and December 2019 were divided into four groups based on their history of hookah and cigarette smoking. The patients’ prospectively collected data, including demographic features, healing time, and presence or absence of septal perforation during follow-up, were compared between these four groups. Results: The entire cohort included 270 patients. The mean patient age was 29.2±5.8 years. One hundred and thirty-two (48.9%) patients were non-smokers, 96 (35.5%) were cigarette smokers, 27 (10%) were hookah smokers, and 15 (5.6%) consumed both tobacco products regularly. Mean healing time was 10 days, and septal perforation was encountered in 10 patients (3.7%). A comparison of the groups revealed that cigarette smoking did not impact septal perforation rates (p=0.326) but prolonged the healing time. However, hookah smoking with or without cigarette smoking significantly influenced septal perforation rates and healing times. Conclusion: Patients should be questioned about hookah smoking in addition to cigarette smoking before the septoplasty procedure. Patients with a positive history of hookah smoking should be followed closely in terms of delayed healing and increased septal perforation rates.

George Angelidis

and 3 more

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 [1]. 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 [2]. 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 [3].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 [4]. 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.

Attila Mokánszki

and 8 more

Background Retinoblastoma (Rb) is a malignant tumor of the developing retina that affects children before the age of five years in association with inherited or early germline mutations of the RB1 gene. The genetic predisposition is also related with second primary malignancies arising de novo, or following radiotherapy which have become the leading cause of death in retinoblastoma survivors. Procedure We describe a retinoblastoma case with a novel RB1 and a synchronous MET aberration. Our goal was to identify all germline and somatic genetic alterations in available tissue samples from different time periods and to reconstruct their clonal relations using next generation sequencing (NGS). We also used structural and functional prediction of the mutant RB and MET proteins to find interactions between the defected proteins with potential causative role in the development of this uniqe form of retinoblastoma. Results In this study we detected a retinoblastoma case of non-parental origin with a novel RB1 c.2548C>T;p.(Gln850Ter) and a synchronous MET c.3029C>T;p.(Thr1010Ile) germline mutations. Following bilateral retinoblastoma the boy further developed at least four different manifestations of two independent osteosarcomas. Both histopathology and NGS findings supported the independent nature of a chondroblastic osteosarcoma of the irradiated facial bone followed by an osteoblastic sarcoma of the leg (tibia). Conclusions Because of the expanding number of registered Rb cases, the novel rare cases publication is very important to understand the molecular mechanism of this malignancy. We reported a novel form of Rb and consequential chondroblastic and osteoblastic osteosarcoma, the latter one developing pulmonary metastatses.

Ugur Balkanci

and 2 more

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.nadir@mayo.eduKey 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.

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