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Respiratory Tract Diseases - Top 30 Publications

Recommended composition of influenza virus vaccines for use in the 2017–2018 northern hemisphere influenza season.

Adherence and Recursive Perception Among Young Adults with Cystic Fibrosis.

Adherence to prescribed treatment is a pressing issue for adolescents and young adults with cystic fibrosis (CF). This paper presents two narratives from the thematic analysis of unstructured interviews with 14 adolescents, young adults, and older adults living with CF. Through a new identity-based framework termed recursive perception that draws focus on how an individual perceives how others view them, it explores the social context of adherence and self-care among young adults with CF. It demonstrates that an individual's understanding of self and desire to maintain a certain image for peers can be deeply embedded in adherence and self-care patterns, leading individuals to feel they need to choose between tending to their health needs and living their lives. This suggests that current biomedical innovation in CF care must be complemented with renewed efforts to find effective means to empower young adults with CF to successfully navigate the social challenges of their illness and avoid the pitfalls of nonadherence that can lead to a permanent worsening of their health condition.

Deep Venous Thrombosis and Pulmonary Embolism: Current Therapy.

Pulmonary embolism and deep venous thrombosis are the two most important manifestations of venous thromboembolism (VTE), which is the third most common life-threatening cardiovascular disease in the United States. Anticoagulation is the mainstay of VTE treatment. Most patients with deep venous thrombosis or low-risk pulmonary embolism can be treated in the outpatient setting with low-molecular-weight heparin and a vitamin K antagonist (warfarin) or direct-acting oral anticoagulants. Inpatient treatment of VTE begins with parenteral agents, preferably low-molecular-weight heparin. Unfractionated heparin is used if a patient is hemodynamically unstable or has severe renal insufficiency, high bleeding risk, hemodynamic instability, or morbid obesity. Direct-acting oral anticoagulants are an alternative; however, concerns include cost and use of reversing agents (currently available only for dabigatran, although others are in development). If warfarin, dabigatran, or edoxaban is used, low-molecular-weight or unfractionated heparin must be administered concomitantly for at least five days and, in the case of warfarin, until the international normalized ratio becomes therapeutic for 24 hours. Hemodynamically unstable patients with a low bleeding risk may benefit from thrombolytic therapy. An inferior vena cava filter is not indicated for patients treated with anticoagulation. Current guidelines recommend anticoagulation for a minimum of three months. Special situations, such as active cancer and pregnancy, require long-term use of low-molecular-weight or unfractionated heparin. Anticoagulation beyond three months should be individualized based on a risk/benefit analysis. Symptomatic distal deep venous thrombosis should be treated with anticoagulation, but asymptomatic patients may be monitored with serial imaging for two weeks and treated only if there is extension.

Anterior condylar confluence dural arteriovenous fistula: a rare cause of hoarseness.

Hoarseness secondary to an anterior condylar confluence (ACC) dural arteriovenous fistula (DAVF) has not been previously described. We present a 58-year-old patient with a 3-week history of progressive unilateral left-sided headaches and hoarseness. Nasolaryngoscopy and CT neck showed the presence of unilateral vocal cord palsy with no identifiable cause along the expected course of the recurrent laryngeal nerve. MRI revealed an incidental finding of abnormal serpiginous vessels in the left hypoglossal canal which led to a diagnostic cerebral angiogram, confirming the presence of an ACC DAVF. The patient underwent transvenous coil embolisation with subsequent resolution of arteriovenous shunting and symptoms. Follow-up MRI at 6 months showed no recurrence and there was complete resolution of clinical symptoms.

Implication of overexpression of dishevelled-associated activator of morphogenesis 1 (Daam-1) for the pathogenesis of human Idiopathic Pulmonary Arterial Hypertension (IPAH).

Idiopathic pulmonary arterial hypertension (IPAH) is a rare, fatal disease of unknown pathogenesis. Evidence from our recent study suggests that IPAH pathogenesis is related to upregulation of the Wnt/planar cell polarity (Wnt/PCP) pathway. We used microscopic observation and immunohistochemical techniques to identify expression patterns of cascading proteins-namely Wnt-11, dishevelled-2 (Dvl-2), and dishevelled-associated activator of morphogenesis 1 (Daam-1)-in pulmonary arteries.

Evaluation of Initial Respiratory Support Strategies in VLBW Neonates with RDS.

Non-invasive ventilation (NIV) has brought about a significant change in care and treatment of respiratory distress syndrome (RDS) in very low birth weight (VLBW) neonates. The present study was designed and conducted to evaluate different strategies of initial respiratory support (IRS) in VLBW neonates hospitalized in the neonatal intensive care unit (NICU).

The Correlation of Decreased Heart Rate Recovery and Chronotropic Incompetence with Exercise Capacity in Idiopathic Pulmonary Arterial Hypertension Patients.

We show by this study that a decrease in HRR1 in IPAH patients is associated with severe limitation of exercise capacity. HRR1 < 16 beats and CI just after completion of a CPET could be an indicator of poor prognosis.

MicroRNA-223 Promotes Tumor Progression in Lung Cancer A549 Cells via Activation of the NF-κB Signaling Pathway.

Our study aimed to investigate the role of microRNA-223 (miR-223) in lung cancer A549 cells and to further elucidate its possible regulatory mechanism. The expression levels of normal human lung epithelial cell line BEAS-2B and human lung cancer cell line A549 were investigated by quantitative real-time PCR. The A549 cells were transfected with miR-223 inhibitor and miR-223 scramble. Afterward, the effects of miR-223 inhibition on cell viability, invasion, and apoptosis, as well as the expression levels of nuclear factor-κB (NF-κB) and its downstream proteins, were detected. In addition, the NF-κB inhibitor JSH-23 was used to detect the relationship between NF-κB and miR-223. miR-223 was upregulated in human lung cancer A549 cells when compared with BEAS-2B cells. In addition, miR-223 expression was successfully inhibited by the miR-223 inhibitor. Suppression of miR-223 significantly decreased cell viability, inhibited invasion, and induced apoptosis of lung cancer A549 cells. Suppression of miR-223 resulted in a significant decrease in the expression levels of NF-κB and its downstream proteins P-IKBα and P-IKKα/β. After treatment with the NF-κB inhibitor, the inhibitory effects of miR-233 inhibitor on cell invasion, as well as the expression levels of NF-κB and p-p65, were enhanced. Our findings indicate that miR-223 may increase proliferation, promote invasion, and inhibit apoptosis of lung cancer A549 cells via activation of the NF-κB signaling pathway. miR-223 may serve as a potential therapeutic target in lung cancer.

Use of a biodegradable, oversized stent in a child with tracheomalacia secondary to vascular external compression.

We describe the implantation of an absorbable, custom-made stent of polydioxanone to treat tracheomalacia in a 5-month-old patient with extrinsic compression by a double aortic arch. The use of an absorbable, oversized stent treated the tracheal collapse caused by vascular compression, avoided removal procedures, and allowed the infant's growth. The use of an oversized stent prevented stent migration and gave minimal problems of granulation.

MicroRNA-Related Polymorphisms in PI3K/Akt/mTOR Pathway Genes Are Predictive of Limited-Disease Small Cell Lung Cancer Treatment Outcomes.

The phosphoinositide-3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway plays an important role in cancer progression and treatment, including that of small cell lung cancer (SCLC), a disease with traditionally poor prognosis. Given the regulatory role of microRNA (miRNA) in gene expression, we examined the association of single nucleotide polymorphisms (SNPs) at miRNA-binding sites of genes in the mTOR pathway with the prognosis of patients with limited-disease SCLC. A retrospective study was conducted of 146 patients with limited-disease SCLC treated with chemoradiotherapy. Nine SNPs of six mTOR pathway genes were genotyped using blood samples. Cox proportional hazard regression modeling and recursive partitioning analysis were performed to identify SNPs significantly associated with overall survival. Three SNPs, MTOR: rs2536 (T>C), PIK3R1: rs3756668 (A>G), and PIK3R1: rs12755 (A>C), were associated with longer overall survival. Recursive partitioning analysis based on unfavorable genotype combinations of the rs2536 and rs3756668 SNPs classified patients into three risk subgroups and was internally validated with 1000 bootstrap samples. These findings suggest that miRNA-related polymorphisms in the PI3K/Akt/mTOR pathway may be valuable biomarkers to complement clinicopathological variables in predicting prognosis of limited-disease SCLC and to facilitate selection of patients likely to benefit from chemoradiotherapy.

Paroxysmal Atrial Fibrillation in the Course of Acute Pulmonary Embolism: Clinical Significance and Impact on Prognosis.

The relationship and clinical implications of atrial fibrillation (AF) in acute pulmonary embolism (PE) are poorly investigated. We aimed to analyze clinical characteristics and prognosis in PE patients with paroxysmal AF episode. Methods. From the 391 patients with PE 31 subjects with paroxysmal AF were selected. This group was compared with patients with PE and sinus rhythm (SR) and 32 patients with PE and permanent AF. Results. Paroxysmal AF patients were the oldest. Concomitant DVT varies between groups: paroxysmal AF 32.3%, SR 49.5%, and permanent AF 28.1% (p = 0.02). The stroke history frequency was 4.6% SR, 12.9% paroxysmal AF, and 21.9% permanent AF (p < 0.001). Paroxysmal AF comparing to permanent AF and SR individuals had higher estimated SPAP (56 versus 48 versus 47 mmHg, p = 0.01) and shorter ACT (58 versus 65 versus 70 ms, p = 0.04). Patients with AF were more often classified into high-risk group according to revised Geneva score and sPESI than SR patients. In-hospital mortality was lower in SR (5%) and paroxysmal AF (6.5%) compared to permanent AF group (25%) (p < 0.001). Conclusions. Patients with PE-associated paroxysmal AF constitute a separate population. More severe impairment of the parameters reflecting RV afterload may indicate relation between PE severity and paroxysmal AF episode. Paroxysmal AF has no impact on short-term mortality.

Bumpy road to the diagnosis of polycythaemia vera.

Polycythaemia vera (PV) is the most common myeloproliferative neoplasm, characterised by increased red cell mass that can present as an unspecified symptom or a thrombohaemorrhagic event. Its diagnosis is based on the presence of erythrocytosis, the identification of the Janus kinase 2 mutation and bone marrow aspirate or biopsy alterations. The challenge of this disease lies on the treatment approach. Its cornerstone is phlebotomy, but depending on the vascular risk, it can include cytoreductive agents, low-dose aspirin or even anticoagulation. We present the case of a 75-year-old woman, whose inaugural presentation of PV was an arterial peripheral occlusion followed by three recurrent events in the same arterial region and a pulmonary embolism. A phlebotomy was initially performed and, after the diagnosis was made, the patient was initiated on low-dose aspirin and anticoagulation with favourable outcome.

Paediatric Active Enhanced Disease Surveillance inaugural annual report, 2014.

The Paediatric Active Enhanced Disease Surveillance (PAEDS) network is a hospital-based active surveillance system employing prospective case ascertainment of selected uncommon vaccine preventable diseases and potential adverse events following immunisation (AEFI). PAEDS enhances other Australian surveillance systems by providing prospective detailed clinical and laboratory data for the same child.

Influenza vaccination coverage among pregnant Indigenous women in the Northern Territory of Australia.

Pregnant Aboriginal and Torres Strait Islander women are at particular risk of severe illness and high attack rates of influenza infection. In Australia, routine seasonal influenza vaccination is currently strongly recommended for all pregnant women and women planning pregnancy, and is provided free of charge for all pregnant women. We sought to determine vaccination coverage, describe the trends and characteristics associated with influenza vaccine uptake and determine the validity of self-reported influenza vaccination in a population of Indigenous pregnant women who were participants of a vaccine trial, prior to and during the 2009 H1N1 influenza pandemic. Vaccine coverage over the study period was 16% (35/214), increasing from 2.2% (3/136) in the period preceding the pandemic (2006-2009) to 41% (32/78) in the intra-pandemic period (2009-2010). Self-report was not a reliable estimate of verified vaccination status in the pre-pandemic period (κ=0.38) but was reliable in the intra-pandemic period (κ=0.91). None of the socio-demographic characteristics that we examined were associated with vaccine uptake. Whilst the increase in maternal influenza coverage rates are encouraging and indicate a willingness of pregnant Indigenous women to be vaccinated, the majority of women remained unvaccinated. Activities to improve influenza vaccination coverage for Indigenous pregnant women and monitor vaccine uptake remain a priority. Commun Dis Intell 2016;40(3):E340-E346.

Increase in Human Infections with Avian Influenza A(H7N9) Virus During the Fifth Epidemic - China, October 2016-February 2017.

During March 2013-February 24, 2017, annual epidemics of avian influenza A(H7N9) in China resulted in 1,258 avian influenza A(H7N9) virus infections in humans being reported to the World Health Organization (WHO) by the National Health and Family Planning Commission of China and other regional sources (1). During the first four epidemics, 88% of patients developed pneumonia, 68% were admitted to an intensive care unit, and 41% died (2). Candidate vaccine viruses (CVVs) were developed, and vaccine was manufactured based on representative viruses detected after the emergence of A(H7N9) virus in humans in 2013. During the ongoing fifth epidemic (beginning October 1, 2016),* 460 human infections with A(H7N9) virus have been reported, including 453 in mainland China, six associated with travel to mainland China from Hong Kong (four cases), Macao (one) and Taiwan (one), and one in an asymptomatic poultry worker in Macao (1). Although the clinical characteristics and risk factors for human infections do not appear to have changed (2,3), the reported human infections during the fifth epidemic represent a significant increase compared with the first four epidemics, which resulted in 135 (first epidemic), 320 (second), 226 (third), and 119 (fourth epidemic) human infections (2). Most human infections continue to result in severe respiratory illness and have been associated with poultry exposure. Although some limited human-to-human spread continues to be identified, no sustained human-to-human A(H7N9) transmission has been observed (2,3).

Pembrolizumab in Non-Small-Cell Lung Cancer.

Levetiracetam-induced eosinophilic pneumonia.

Levetiracetam is widely regarded as a benign antiepileptic drug, compared to older antiepileptic medication. We report a case of eosinophilic pneumonia due to levetiracetam use in a non-smoking woman aged 59 years with no previous respiratory history. Our patient presented with exertional breathlessness and marked desaturation on exertion. She displayed 'reverse bat-wing' infiltrates on her chest radiograph and peripheral eosinophilia on a complete blood count. Her symptoms, radiology and peripheral eosinophilia resolved completely with cessation of levetiracetam and a course of prednisolone. This is the first report of isolated eosinophilic pneumonia due to levetiracetam. Other reports of levetiracetam-induced eosinophilia describe drug rash, eosinophilia and systemic symptoms (DRESS syndrome). Detection of pulmonary drug reactions requires a careful drug history and high index of suspicion. Identifying and reporting a causative agent is crucially important, as cessation of the drug is essential for resolution of the syndrome.

Pembrolizumab in Non-Small-Cell Lung Cancer.

Multiple primary malignancies of laryngeal cancer, small cell lung cancer and squamous cell lung cancer in a patient: how to approach MPMs.

Lung malignancies presenting in association with head and neck cancers are well documented, while laryngeal cancers presenting with simultaneous small cell lung cancer and squamous cell lung cancer have been rarely reported. We report a case of a man aged 65 years with a triple primary malignancy of the lung and larynx. Without a meticulous approach, the patients may not receive curative aim treatment due to incomplete staging. The patient underwent concurrent chemoradiotherapy for locally advanced laryngeal cancer, small cell lung cancer and squamous cell lung cancer followed by combination chemotherapy with etoposide and cisplatin for synchronous double primary lung cancer. Following this therapy, he achieved a complete response of larynx cancer, but a partial response of small cell lung cancer and a stable disease of squamous cell lung cancer. A meticulous diagnostic approach should be encouraged to pursue the possibility of curative treatment and achieve better outcomes for such patients.

Genetic analyses of the fusion protein genes in human parainfluenza virus types 1 and 3 among patients with acute respiratory infections in Eastern Japan from 2011 to 2015.

To genetically explore the fusion protein gene (F) in human parainfluenza virus type 1 (HPIV1) and type 3 (HPIV3) strains, we analysed them in patients with acute respiratory infections in Eastern Japan from 2011 to 2015.

IL33 and IL1RL1 variants are associated with asthma and atopy in a Brazilian population.

Atopic asthma is a chronic inflammatory disease in airways resulting from genetic and environmental factors, characterized by production of the Th2 cytokines interleukin-4 (IL-4), interleukin-5 (IL-5) and interleukin-13 (IL-13). Interleukin-33 (IL-33) appears to be a potent inducer of Th2 immune response. This occurs when IL-33 binds and activates its receptor, the membrane ST2 (ST2L) in mast cells, dendritic cells, basophils, eosinophils, innate lymphoids and Th2 cells, leading to the release of these cytokines and intensifying allergic inflammation. Polymorphisms in the IL33 and IL1RL1 can act as protective or risk factors for asthma and/or allergy in humans. No study was conducted to replicate such findings in a European and African descendent mixed population. DNA was extracted from peripheral blood from 1223 subjects, and the samples were genotyped using Illumina 2.5 Human Omni Beadchip. We tested for possible associations between SNPs in the IL33 and ST2 with asthma and allergy markers such as specific IgE (sIgE), IL-5 and IL-13 production and skin prick test (SPT). Logistics regressions were performed using PLINK software 1.07. The analyses were adjusted for sex, age, helminth infection and ancestry markers. The G allele of IL33 SNP rs12551256 was negatively associated with asthma (OR 0.71, 95% CI: 0.53-0.94, P = 0.017). In contrast, the A allele of IL1RL1 rs1041973 was positively associated with IL-5 production (OR 1.36, 95% CI: 1.09-1.84, P = 0.044), sIgE levels (OR 1.40, 95% CI: 1.07-1.84, P = 0.013) and positive SPT (OR 1.48, 95% CI: 1.08-2.03, P = 0.014), for Blomia tropicalis mite. The same allele, in atopic subjects, was associated with decreased production of soluble ST2 (sST2) (P < 0.05). Moreover, expression quantitative trait loci (eQTL) analysis suggests that rs1041973 and rs873022 regulate the expression of IL1RL1 gene. This latest SNP, rs873022, the T allele, was also associated with a lower production of sST2 in plasma of Brazilians. The genetic risk score for rs1041973 and rs16924161 demonstrated a higher risk for SPT positivity against B. tropicalis, the greater the number of risk alleles for both SNPs. Our findings demonstrate a robust association of genetic variants in IL1RL1 and IL33 SNPs with allergy markers and asthma.

Unusual presentation of a late-onset recurrence of malignant peritoneal mesothelioma.

A man aged 79 years with a history of malignant peritoneal mesothelioma presented 8 years after primary presentation with a suspected right-sided painful inguinal hernia and hydrocele, both present for 5 months. During surgery, however, the inguinal swelling appeared to be a tumour. Laboratory examination was non-alarming and ultrasonography not specific for mesothelioma. Pathological examination showed it to be a recurrence of the malignant mesothelioma, which was treated palliative with radiotherapy. This clinical picture is rare and a recurrence-free survival of 8 years is remarkable.

Multidisciplinary approach to the management of a case of classical respiratory diphtheria requiring percutaneous endoscopic gastrostomy feeding.

We present a case of a Caucasian woman aged 67 years referred with a 4-day history of sore throat, dysphagia, fever and nasal blockage. Examination revealed a swollen neck and pharyngeal pseudomembrane. A throat swab was positive on culture for Corynebacterium ulcerans, with toxin expression confirmed on PCR and Elek testing. A diagnosis of classical respiratory diphtheria was made, with subsequent confirmation of the patient's domesticated dog as the source of infection. The dog had recently been attacked by a wild badger and was being treated for an ear infection. The patient made a good recovery with intravenous antimicrobial and supportive therapy; however, she subsequently developed a diphtheritic polyneuropathy in the form of a severe bulbar palsy with frank aspiration necessitating percutaneous endoscopic gastrostomy feeding. A mild sensorimotor peripheral neuropathy was also diagnosed. The patient eventually made an almost complete recovery.

Reducing Exposure to Mouse Allergen Among Children and Adolescents With Asthma Is Achievable, but Is It Enough?

The accumulation of lipids and proteins during red blood cell storage: the roles of leucoreduction and experimental filtration.

Pre-storage leucoreduction has been universally adopted in most developed countries in Asia, Europe and the Americas. It decreases febrile transfusion reactions, alloimmunisation to HLA antigens, cytomegalovirus exposure, the accumulation of a number of pro-inflammatory mediators in the supernatant, including the accumulation of platelet-and leucocyte-derived proteins and metabolites during routine storage. This review will highlight the lipids and proteins, biological response modifiers (BRMs) that accumulate, their clinical effects in transfused hosts, and methods of mitigation.

The red cell storage lesion(s): of dogs and men.

The advent of preservative solutions permitted refrigerated storage of red blood cells. However, the convenience of having red blood cell inventories was accompanied by a disadvantage. Red cells undergo numerous physical and metabolic changes during cold storage, the "storage lesion(s)". Whereas controlled clinical trials have not confirmed the clinical importance of such changes, ethical and operational issues have prevented careful study of the oldest stored red blood cells. Suggestions of toxicity from meta-analyses motivated us to develop pre-clinical canine models to compare the freshest vs the oldest red blood cells. Our model of canine pneumonia with red blood cell transfusion indicated that the oldest red blood cells increased mortality, that the severity of pneumonia is important, but that the dose of transfused red blood cells is not. Washing the oldest red blood cells reduces mortality by removing senescent cells and remnants, whereas washing fresher cells increases mortality by damaging the red blood cell membrane. An opposite effect was found in a model of haemorrhagic shock with reperfusion injury. Physiological studies indicate that release of iron from old cells is a primary mechanism of toxicity during infection, whereas scavenging of cell-free haemoglobin may be beneficial during reperfusion injury. Intravenous iron appears to have toxicity equivalent to old red blood cells in the pneumonia model, suggesting that intravenous iron and old red blood cells should be administered with caution to infected patients.

Peritonsillar abscess: clinical aspects of microbiology, risk factors, and the association with parapharyngeal abscess.

PTA is a collection of pus located between the tonsillar capsule and the pharyngeal constrictor muscle. It is considered a complication of acute tonsillitis and is the most prevalent deep neck infection (approximately 2000 cases annually in Denmark) and cause of acute admission to Danish ENT departments. Teenagers and young adults are most commonly affected and males may predominate over females. However, no studies of age- and gender-stratified incidence rates have previously been published. Furthermore, smoking may be associated with increased risk of peritonsillar abscess (PTA) development, although the magnitude of the association has not been estimated. Complications are relatively rare. They include parapharyngeal abscess (PPA), upper airway obstruction, Lemierre´s syndrome, necrotizing fasciitis, mediastinitis, erosion of the internal carotid artery, brain abscess, and streptococcal toxic shock syndrome. The treatment consists of abscess drainage and antimicrobial therapy. There are three accepted methods of surgical intervension: needle aspiration, incision and drainage (ID), and acute tonsillectomy (á chaud). Internationally, there is a strong trend towards less invasive surgical approach to PTA treatment with avoidance of acute tonsillectomy, needle aspiration instead of ID, and in some cases even antibiotic treatment without surgical drainage. The preferred antibiotic regimen varies greatly between countries and centers. Group A streptococcus (GAS) is the only established pathogen in PTA. However, GAS is only recovered from approximately 20% of PTA patients. The pathogens in the remaining 80% are unknown. Culturing of PTA pus aspirates often yields a polymicrobial mixture of aerobes and anaerobes. As the tonsils of healthy individuals are already heavily and diversely colonized, the identification of significant pathogens is challenging. In addition, when studying PTA microbiology, one must consider diagnostic precision, collection, handling, and transportation of appropriate specimens, choice of methodology for detection and quantification of microorganisms, current or recent antibiotic treatment of patients, potential shift in significant pathogens during the course of infection, and factors associated with increased risk of PTA development.  The trend towards de-escalated surgical intervention and increasing reliance on antibiotic treatment, require studies defining the significant pathogens in PTA in order to determine optimal antibiotic regimens. Complications secondary to PTA may be avoided or better controlled with improved knowledge concerning the significant pathogens in PTA. Furthermore, identification of pathogens other than GAS, may lead the way for earlier bacterial diagnosis and timely intervention before abscess formation in sore throat patients. The identification and quantification of risk factors for PTA development constitutes another approach to reduce the incidence of PTA. As clinicians, we noticed that FN was recovered from PTA patients with increasing frequency and that patients infected with Fusobacterium necrophorum (FN) seemed to be more severely affected than patients infected with other bacteria. Furthermore, we occationally observed concomitant PPA in addition to a PTA, which made us hypothesize that PPA and PTA is often closely related and may share significant pathogens. Hence, our aims were: 1. To explore the microbiology of PTA with a special attention to Fusobacterium necrophorum (FN). 2. To elucidate whether smoking, age, gender, and seasons are risk factors for the development of PTA. 3. To characterize patients with PPA, explore the relationship between PPA and PTA, identify the pathogens associated with PPA, and review our management of PPA. In a retrospective study on all 847 PTA patients admitted to the ENT department at Aarhus University Hospital (AUH) from 2001 to 2006, we found that FN was the most prevalent (23%) bacterial strain in pus specimens. FN-positive patients displayed significantly higher infection markers (CRP and neutrophil counts) than patients infected with other bacteria (P = 0.01 and P < 0.001, respectively). In a subsequent prospective and comparative study on 36 PTA patients and 80 patients undergoing elective tonsillectomy (controls), we recovered FN from 58% of PTA aspirates. Furthermore, FN was detected significantly more frequently in the tonsillar cores of PTA patients (56%) compared to the tonsillar cores of the controls (24%) (P = 0.001). We also analysed sera taken acutely and at least two weeks after surgery for the presence of anti-FN antibodies. We found increasing levels (at least two-fold) of anti-FN antibodies in eight of 11 FN-positive (in the tonsillar cultures) PTA patients, which was significantly more frequent compared to none of four FN-negative PTA patients and nine of 47 electively tonsillectomized controls (P = 0.026 and P < 0.001, respectively). Blood cultures obtained during acute tonsillectomy mirrored the bacterial findings in the tonsillar specimens with 22% of patients having bacteremia with FN. However, bacteremia during elective tonsillectomy was at least as prevalent as bacteremia during quinsy tonsillectomy, which challenges the distinction made by the European Society of Cardiology between quinsy and elective tonsillectomy, namely that antibiotic prophylaxis is only recommended to patients undergoing procedures to treat an established infection (i.e. PTA). Using PCR analysis for the presence of herpes simplex 1 and 2, adenovirus, influenza A and B, Epstein-Barr virus (EBV), and respiratory syncytial virus A and B, we explored a possible role of viruses in PTA. However, our results did not indicate that any of these viruses are involved in the development of PTA. Privious studies have documented an association between EBV and PTA in approximately 4% of PTA cases. In addition to the involvement of GAS, the following findings suggest a pathogenic role for FN in PTA: 1. Repeated high isolation rates of FN in PTA pus aspirates. 2. Higher isolation rates in PTA patients compared to electively tonsillectomised controls. 3. Development of anti-FN antibodies in FN-positive patients with PTA. 4. Significantly higher inflammatory markers in FN-positive patients compared to PTA patients infected with other bacteria. We studied the smoking habits among the same 847 PTA patients admitted to the ENT department, AUH from 2001 to 2006. We found that smoking was associated with increased risk of PTA for both genders and across all age groups. The increased risk of PTA among smokers was not related to specific bacteria. Conclusions on causality cannot be drawn from this retrospective study, but the pathophysiology behind the increased risk of PTA in smokers may be related to, previously shown, alterations in the tonsillar, bacterial flora or the local and systemical inflammatory and immunological milieu. Studying all 1,620 patients with PTA in Aarhus County from 2001 to 2006 and using population data for Aarhus County for the same six years, age- and gender-stratified mean annual incidence rates of PTA were calculated. The incidence of PTA was highly related to age and gender. The seasonal variation of PTA was insignificant. However, the microbiology of PTA fluctuated with seasons: GAS-positive PTA cases were significantly more prevalent in the winter and spring compared to the summer, while FN-positive PTA patients exhibited a more even distribution over the year, but with a trend towards higher prevalence in the summer than in the winter. In a series of 63 patients with PPA, we found that 33 (52%) patients had concomitant PTA. This association between PPA and PTA was much higher than previously documented. We therefore suggest that combined tonsillectomy and intrapharyngeal incision in cases where PTA is present or suspected. The results of our routine cultures could not support a frequent role of FN in PPA. Based on our findings suggesting that FN is a frequent pathogen in PTA, we recommend clindamycin instead of a macrolide in penicillin-allergic patients with PTA. Furthermore, cultures made from PTA aspirates should include a selective FN-agar plate in order to identify growth of this bacterium. Recent studies of sore throat patients document an association between recovery of FN and acute tonsillitis. Studying the bacterial flora of both tonsils in study II, we found almost perfect concordance between the bacterial findings of the tonsillar core at the side of the abscess and contralaterally. This finding suggests that FN is not a subsequent overgrowth phenomenon after abscess development, but that FN can act as pathogen in severe acute tonsillitis. Future studies of patients with FN-positive acute tonsillitis focusing on the optimal methods (clinical characteristics, culture, polymerase chain reaction, or other) for diagnosis and whether antibiotics (and which) can reduce symptoms and avoid complications are warranted. Until further studies are undertaken, we recommend clinicians to have increased focus on acute tonsillitis patients aged 15-24 years with regards to symptoms and findings suggestive of incipient peritonsillar involvement. We have conducted a number of studies with novel findings: 1. FN is a significant and prevalent pathogen in PTA. 2. Bacteremia during abscess tonsillectomy is no more prevalent than during elective tonsillectomy. 3. The development of anti-FN antibodies in FN-positive PTA patients. We have used novel approaches as principles to suggest pathogenic significance of candidate microorganisms: 1. Comparative microbiology between PTA patients and "normal tonsils". 2. Measurements indicating larger inflammatory response compared to clinically equivalent infection.

Chemotherapy-related acute respiratory distress syndrome in germ cell tumors: a literature review.

Germ cell tumors (GCTs) are one of the more curable solid cancers in men. Approximately 8500 men are diagnosed with GCTs in the USA. The majority of patients survive due to the availability of effective treatment. Fewer than 400 men are estimated to die from their disease. Among those, there is a subset of patients with metastatic GCTs receiving chemotherapy who rapidly develop progressive respiratory failure and die during the early phase of their treatment course. In this review, we searched the available literature for reported cases and retrospective series of chemotherapy-associated acute respiratory distress syndrome in GCTs. We aim to determine whether a different approach from current treatment guidelines could be considered to prevent this catastrophic chemotherapy-related event.

Associations of Adenovirus Genotypes in Korean Acute Gastroenteritis Patients with Respiratory Symptoms and Intussusception.

Human adenoviruses (HAdVs) cause a wide range of diseases, including respiratory infections and gastroenteritis, and have more than 65 genotypes. To investigate the current genotypes of circulating HAdV strains, we performed molecular genotyping of HAdVs in the stool from patients with acute gastroenteritis and tried to determine their associations with clinical symptoms. From June 2014 to May 2016, 3,901 fecal samples were tested for an AdV antigen, and 254 samples (6.5%) yielded positive results. Genotyping using PCR and sequencing of the capsid hexon gene was performed for 236 AdV antigen-positive fecal specimens. HAdV-41, of species F, was the most prevalent genotype (60.6%), followed by HAdV-2 of species C (13.8%). Other genotypes, including HAdV-3, HAdV-1, HAdV-5, HAdV-6, HAdV-31, HAdV-40, HAdV-12, and HAdV-55, were also detected. Overall, 119 patients (50.4%) showed concomitant respiratory symptoms, and 32 patients (13.6%) were diagnosed with intussusception. HAdV-1 and HAdV-31 were significantly associated with intussusception (P < 0.05). Our results demonstrate the recent changes in trends of circulating AdV genotypes associated with gastroenteritis in Korea, which should be of value for improving the diagnosis and developing new detection, treatment, and prevention strategies for broad application in clinical laboratories.

Management of brain metastasized non-small cell lung cancer (NSCLC) - From local treatment to new systemic therapies.

Lung cancer has the highest frequency of brain dissemination compared to all other solid tumours. Classical treatment options such as brain irradiation have started to be questioned due to lack of survival benefit and risk for severe side effects. Oncogenic driven tumours have the highest frequency of brain dissemination among NSCLC patients and available targeted therapies have shown activity both intra-and extracranially, with an acceptable toxicity profile. The recent approval of immune checkpoint inhibitors for the treatment of NSCLC has complicated treatment selection even more. Data regarding efficacy of immune therapy in the CNS are limited, though promising, and data from larger cohorts are eagerly expected. The purpose of this review is to summarize all available treatment options for brain metastatic NSCLC with an emphasis on oncogenic driven tumours. Treatment selection for brain metastasized NSCLC patients is challenging because of the detrimental effect of potential treatment related CNS side effects in patients' quality of life. Clinical decision making should be done in an individualised way, taking both clinical and molecular factors into consideration.