Microbial aetiology of acute rhinosinusitis during pregnancy.

BACKGROUND: Pregnancy as an immunosuppressive condition and with the associated tendency for mucosal oedema can predis- pose women to acute rhinosinusitis. Our hypothesis was that pregnancy enhances opportunistic sinus infections. METHODOLOGY: We retrospectively collected data on pregnant women with acute rhinosinusitis treated at the Department of Otorhinolaryngology, Helsinki University Hospital, Finland in 2010-2015. Maxillary puncture was performed on all patients, and patients with purulent sinus secretions and bacterial culture were included in the study. Clinical data on patients and microbial findings of bacterial cultures were recorded and compared with those of non-pregnant controls. RESULTS: Ninety-five pregnant patients and 91 controls were included. The bacterial cultures of pregnant patients revealed bac- terial growth more often than control patients’ specimens (78.9% vs. 54.9%). The most common bacterial findings (pregnant vs. control patients) were Streptococcus pneumoniae 43.2% vs. 20.9%, Haemophilus influenzae 22.1% vs. 16.5%, and Moraxella catar- rhalis 10.5% vs. 2.2%. S. pneumoniae was the most frequent finding in all trimesters, and the proportion of S. pneumoniae sinusitis was highest during the last trimester of pregnancy. CONCLUSIONS: The pathogens of acute rhinosinusitis in pregnant patients are the same as in non-pregnant patients, however, the proportions differ; during pregnancy S. pneumoniae infection is more frequent.

Complications and number of follow-up visits after using septal stapler in septoplasty.

BACKGROUND: Septoplasties have traditionally been closed with transseptal sutures, silicone splints, or packing with nasal tamponade. In 2015, our clinic began to employ a septal stapler. The stapler adheres the mucosa to the septal cartilage with bioresorbable staples, replacing both sutures and silicone splints and limiting the use of nasal tamponade for bleeding cases. The complications of stapler versus other methods have not been reported on previously. Thus, the aim of this study was to investigate whether the use of stapler in septoplasties makes a difference in complication rates, operation time, or number of follow-up visits when compared to the traditional closure or filling methods. METHODOLOGY: Patient records from 101 septoplasties in which the stapler had been used, and a reference group of 356 septoplasties in which the stapler had not been used, were retrospectively reviewed and analysed. RESULTS: No significant difference was seen in the complication rate between the stapler and the control group. Overall follow-up visits were fewer in the stapler group when compared to the control group, however there was no significant difference in the number of unplanned follow-up visits between the groups. CONCLUSIONS: By using the stapler in septoplasty, the number of postoperative follow-up visits might be reduced. Neither complication rate, nor operation time differed when using the stapler as compared to the traditional methods of closure.

Patient injuries in operative rhinology during a ten-year period: Review of national patient insurance charts.

OBJECTIVES: To assess factors contributing to patient injuries in operative rhinology. DESIGN: Data of the accepted patient injury claims involving operative rhinology, between the years 2001 and 2011, were obtained from the Finnish Patient Insurance Centre registry. Two senior otolaryngologists analysed and evaluated the injury mechanisms. MAIN OUTCOME MEASURES: Analysis and classification of factors contributing to patient injuries. RESULTS: During the ten-year study period, there were 67 patient injuries in operative rhinology, comprising 36% of all patient injuries in otorhinolaryngologic surgery. The majority (78%) of patients were treated in university or central hospitals and almost all (90%) by fully trained otolaryngology specialists. The factors contributing to the injuries were errors in surgical technique, like lesions to the orbit, skull base and meninges, and adjacent nerves, as well as mistakes with removable packings left in situ. Nearly half of the patients had undergone endoscopic sinus surgery. One patient died because of bleeding from the intracranial artery. Fourteen patients (21%) needed a re-operation due to the injury. CONCLUSIONS: Patient injuries in rhinology were caused by typical complications of common operations performed by otorhinolaryngology specialists. The increased volume of endoscopic sinus surgery was evident also in patient injuries.

Renewal of peritonsillar abscess: Impact of the bacterial species of the infection and clinical features of the patient-A prospective comparative aetiological study.

OBJECTIVES: To compare the bacterial species and patient clinical features in peritonsillar abscesses between patients who had renewal (renewal group) and those who did not (recovery group). DESIGN: Prospective comparative aetiological study. SETTING: Tertiary referral centre. PARTICIPANTS: A total of 180 adult peritonsillar abscess patients were prospectively enrolled and treated as outpatients with incision and drainage and oral antibiotics. Bacteria from the pus were evaluated with a microarray assay. All contact with the healthcare system and renewal of the symptoms were recorded. MAIN OUTCOME MEASURES: Different bacterial species and patient clinical features between the renewal and recovery groups. RESULTS: Of the 180 enrolled patients, 18 experienced a renewal of symptoms. Bacteria from the Streptococcus anginosus group were detected in the patient samples of the renewal group more often than in those of the recovery group (P=.002). No isolated Streptococcus pyogenes samples were reported in the renewal group, while in the recovery group it was reported on 24% of the patients (P=.014). In the renewal group, patients over age 40 experienced symptom renewal faster than the younger patients (P=.013) and were more likely to be male (P=.036). CONCLUSIONS: Bacteria in the Streptococcus anginosus group appear to predict renewal of PTA symptoms, while Streptococcus pyogenes was not found in our patients with symptom renewal. Certain subgroups of patients should be followed more closely.

Towards better patient safety in otolaryngology: characteristics of patient injuries and their relationship with items on the WHO Surgical Safety Checklist.

OBJECTIVES: Increasing knowledge of factors contributing to medical adverse events has influenced the development of preventive policies and protocols, the WHO Surgical Safety Checklist being the most widely known. Despite growing evidence of the checklist's effectiveness in surgery, its role in preventing adverse events in otolaryngology is unclear. We assessed patient injury-contributing factors in otolaryngology and their relationship with WHO checklist items. STUDY DESIGN: A retrospective claim record study of national patient insurance charts in Finland. SETTING AND PARTICIPANTS: The records of all accepted patient injury claims in otolaryngology between 2001 and 2011 were searched and reviewed by two otolaryngologists. Operation-related injuries were evaluated in detail. Factors contributing to injury were identified, classified and compared with items on the WHO checklist. We also estimated whether the injury might have been prevented with a properly used checklist. RESULTS: In the 10-year study period, 188 (84.3%) of the 223 patient injuries were associated with operative care. Of these, 142 (75.5%) occurred in the operation theatre, and in 121 cases (64.4%), technical error in performing surgery was the primary cause of injury. In 18 injuries (9.6%), the error corresponded to a checklist item. Nine injuries (4.8%) could have been prevented with a properly used checklist. CONCLUSIONS: Patient injuries in otolaryngology are strongly related to operative care. The WHO checklist is one suitable tool for error prevention.

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015.

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as 'accidental cell death' (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. 'Regulated cell death' (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death.

Microarray identification of bacterial species in peritonsillar abscesses.

Peritonsillar abscess (PTA) is the most common otorhinolaryngological infection, requiring management at the special healthcare level. The microbiological findings vary due to geographical, etiological, and methodological factors. This study aimed to identify the bacterial species of PTAs by using a novel polymerase chain reaction (PCR)- and microarray-based assay, and to find causative cofactors among patients with different pathogens. We determined the bacterial findings of aspirates of pus prospectively collected from 180 PTA patients. Samples were pretreated prior to nucleic acid extraction and analyzed with a PCR- and microarray-based assay or DNA sequencing. Both methods were based on the gyrB/parE topoisomerase genes. Patients answered symptom questionnaires at admission, and their medical records were reviewed later. Altogether, 160 (89 %) aspirates of pus tested positive for bacteria, and a bacterial species was identified in 149 (83 %) of the samples. A polybacterial species was detected in 20 (13 %) and anaerobic bacteria in 77 (52 %) of the 149 samples. Fusobacterium necrophorum patients were younger (p < 0 .001) and had more severe symptoms (p = 0.04) than patients with other pathogens. Gender, smoking, or preadmission antibiotics showed no correlation with any of the pathogens. Although requiring some optimization, this microarray assay seems feasible and fast for bacterial identification directly from pus samples, and confirms the diversity of PTA pathogens. Young patients with more severe symptoms may require special attention. Species-specific antibiotic treatment of PTA remains challenging due to bacterial variations; the present assay may aid in specifying PTA antibiotic treatment in the future.

Lipopolysaccharide sensitized male and female juvenile brains to ionizing radiation.

Radiotherapy is an effective tool in the treatment of pediatric malignancies but it is associated with adverse side effects, both short- and long-term. One common long-term side effect after cranial radiotherapy is cognitive impairment and this is, at least partly, thought to be caused by reduced hippocampal neurogenesis. Neuroinflammation and a perturbed microenvironment are thought to be important in the dysregulation of neurogenesis seen after irradiation (IR). We investigated the effects of a pre-existing, lipopolysaccharide (LPS)-induced systemic inflammation at the time of IR in both males and females. A single dose of 8 Gy to the brain of postnatal day 14 mice caused an upregulation of cytokines/chemokines (IL-1ß, MIP-1ß, IL-12, GM-CSF, MIP-1α, IL-17, CCL2 and KC) 6 h after IR, more so in females. Caspase-3 activity, reflecting apoptosis and possibly microglia activation, was elevated 6 h after IR. Females treated with LPS before IR showed a higher caspase-3 activity compared with males. During the chronic phase (3 months post IR), we found that LPS-induced inflammation at the time of IR aggravated the IR-induced injury in both male and female mice, as judged by reduced bromodeoxyuridine incorporation and neurogenesis (doublecortin-positive cells) in the hippocampus. At this late time point, the microglia density was increased by IR, more so in females, indicating long-term effects on the microenvironment. IR increased anxiety-related behavior in vehicle-, but not LPS-, treated animals. However, exploratory behavior was affected by IR in both vehicle- and LPS-treated mice. In conclusion, we found that LPS administration before IR of the young mouse brain aggravated the injury, as judged by reduced hippocampal neurogenesis. This supports the clinical practice to postpone radiotherapy if the patient shows signs of infection. Systemic inflammation is not always obvious, though, for example because of concurrent corticosteroid treatment, so careful monitoring of inflammation is warranted.

Irradiation to the young mouse brain impaired white matter growth more in females than in males.

Modern therapy cures 80% of all children with brains tumors, but may also cause long-lasting side effects, so called late effects. Radiotherapy is particularly prone to cause severe late effects, such as intellectual impairment. The extent and nature of the resulting cognitive deficits may be influenced by age, treatment and gender, where girls suffer more severe late effects than boys. The reason for this difference between boys and girls is unknown, but very few experimental studies have addressed this issue. Our aim was to investigate the effects of ionizing radiation on the corpus callosum (CC) in both male and female mice. We found that a single dose of 8 Gray (Gy) to the brains of postnatal day 14 mice induced apoptosis in the CC and reduced the number of proliferating cells by one third, as judged by the number of phospho-histone H3 positive cells 6 h after irradiation (IR). BrdU incorporation was reduced (62% and 42% lower in females and males, respectively) and the number of oligodendrocytes (Olig2(+) cells) was lower (43% and 21% fewer in females and males, respectively) 4 months after IR, so the lack of developing and differentiated cells was more pronounced in females. The number of microglia was unchanged in females but increased in males at this late time point. The density of microvessel profiles was unchanged by IR. This single, moderate dose of 8 Gy impaired the brain growth to some extent (8.1% and 0.4% lower brain/body weight ratio in females and males, respectively) but the CC growth was even more impaired (31% and 19% smaller in females and males, respectively) 4 months after IR compared with non-irradiated mice. In conclusion, this is the first study to our knowledge demonstrating that IR to the young rodent brain affects white matter development more in females than in males.

Anaesthetic neurotoxicity and neuroplasticity: an expert group report and statement based on the BJA Salzburg Seminar.

Although previously considered entirely reversible, general anaesthesia is now being viewed as a potentially significant risk to cognitive performance at both extremes of age. A large body of preclinical as well as some retrospective clinical evidence suggest that exposure to general anaesthesia could be detrimental to cognitive development in young subjects, and might also contribute to accelerated cognitive decline in the elderly. A group of experts in anaesthetic neuropharmacology and neurotoxicity convened in Salzburg, Austria for the BJA Salzburg Seminar on Anaesthetic Neurotoxicity and Neuroplasticity. This focused workshop was sponsored by the British Journal of Anaesthesia to review and critically assess currently available evidence from animal and human studies, and to consider the direction of future research. It was concluded that mounting evidence from preclinical studies reveals general anaesthetics to be powerful modulators of neuronal development and function, which could contribute to detrimental behavioural outcomes. However, definitive clinical data remain elusive. Since general anaesthesia often cannot be avoided regardless of patient age, it is important to understand the complex mechanisms and effects involved in anaesthesia-induced neurotoxicity, and to develop strategies for avoiding or limiting potential brain injury through evidence-based approaches.

Grafting of neural stem and progenitor cells to the hippocampus of young, irradiated mice causes gliosis and disrupts the granule cell layer.

Ionizing radiation persistently reduces the pool of neural stem and progenitor cells (NSPCs) in the dentate gyrus (DG) of the hippocampus, which may explain some of the learning deficits observed in patients treated with radiotherapy, particularly pediatric patients. A single dose of 8 Gy irradiation (IR) was administered to the brains of postnatal day 14 (P14) C57BL/6 mice and 1.0 × 10(5) bromodeoxyuridine-labeled, syngeneic NSPCs were injected into the hippocampus 1 day, 1 week or 6 weeks after IR. Cell survival and phenotype were evaluated 5 weeks after grafting. When grafted 1 day post-IR, survival and neuronal differentiation of the transplanted NSPCs were lower in irradiated brains, whereas the survival and cell fate of grafted cells were not significantly different between irradiated and control brains when transplantation was performed 1 or 6 weeks after IR. A young recipient brain favored neuronal development of grafted cells, whereas the older recipient brains displayed an increasing number of cells developing into astrocytes or unidentified cells. Injection of NSPCs, but not vehicle, induced astrogliosis and reduced thickness of the dorsal blade of the GCL after 5 months. In summary, we demonstrate that age and interval between IR and grafting can affect survival and differentiation of grafted NSPCs. The observed long-term gliosis and degeneration warrant caution in the context of NSPC grafting for therapeutical purposes.

Prevention of relapses of nasal polyposis with intranasal triamcinolone acetonide after polyp surgery: a prospective double-blind, placebo-controlled, randomised study with a 9-month follow-up.

OBJECTIVE: To determine whether intranasal triamcinolone acetonide prevents the regrowth of nasal polyps after polyp surgery. STUDY DESIGN: Randomised, double-blind, placebo-controlled, prospective study. SETTING: Helsinki University Central Hospital. PARTICIPANTS: Sixty patients with nasal polyps entered the study. Patients were included upon arrival for elective polyp operations determined according to our standard clinical criteria. The recurrence of nasal polyposis was followed up for 9 months after surgical treatment at 3-month intervals. MAIN OUTCOME MEASURES: Anterior rhinoscopy, nasal endoscopy, olfactory threshold measurement, active anterior rhinomanometry and acoustic rhinometry were performed at every follow-up visit. RESULTS: On the whole, there was a significant inter-group difference in the change in polyp size of acetylsalicylic acid (ASA)-tolerant patients during the follow-up. In patients with acetylsalicylic acid intolerance, there was no inter-group difference (P = 0.28). No significant differences were noted for nasal resistance, nasal cavity volume, sense of smell and nasal symptoms. CONCLUSION: Triamcinolone acetonide prevents regrowth of nasal polyps after polyp surgery in acetylsalicylic acid-tolerant patients, but not in acetylsalicylic acid-intolerant patients.

A pilot study of the implementation of WHO surgical checklist in Finland: improvements in activities and communication.

BACKGROUND: World Health Organisation (WHO) has introduced a surgical safety checklist that has reduced post-operative morbidity and mortality. Prior to national checklist implementation, we assessed its possible impact on the operating room (OR) process, safety-related issues and communication among surgical staff in a high-income country. METHODS: In four university and teaching hospitals, a structured questionnaire was delivered to OR personnel involved in consecutive operations over 4-6 weeks before and after the checklist implementation. The questionnaire resembled the WHO checklist and comprised multiple-choice questions relating to performance of safety checks and communication. Anaesthesiologists (A), surgeons (S) and circulating nurses (CN) answered the questions independently. The WHO checklist was modified for national needs. RESULTS: Questionnaires were returned from 1748 operations, 901 before and 847 after the checklist. Patient's identity was more often confirmed (A: 62.7% vs. 84.0%, S: 71.6% vs. 85.5%, CN: 81.6% vs. 94.2%, P < 0.001) and knowledge of names and roles among team members (A: 65.7% vs. 81.8%, S: 71.1% vs. 83.6%, CN: 87.7% vs. 93.2%, P < 0.01) improved with the checklist. Anaesthesiologists and surgeons discussed critical events pre-operatively (A: 22.0% vs. 42.6%, S: 34.7% vs. 46.2%, P < 0.001) more frequently after the checklist. In addition, fewer communication failures (43 vs. 17, P < 0.05) were reported with checklist. CONCLUSIONS: The checklist increased OR teams' awareness of patient-related issues, the procedure and expected risks. It also enhanced team communication and prevented communication failures. Our findings support use of the WHO checklist in various surgical fields.

Induction of ER stress in response to oxygen-glucose deprivation of cortical cultures involves the activation of the PERK and IRE-1 pathways and of caspase-12.

Disturbance of calcium homeostasis and accumulation of misfolded proteins in the endoplasmic reticulum (ER) are considered contributory components of cell death after ischemia. However, the signal-transducing events that are activated by ER stress after cerebral ischemia are incompletely understood. In this study, we show that caspase-12 and the PERK and IRE pathways are activated following oxygen-glucose deprivation (OGD) of mixed cortical cultures or neonatal hypoxia-ischemia (HI). Activation of PERK led to a transient phosphorylation of eIF2α, an increase in ATF4 levels and the induction of gadd34 (a subunit of an eIF2α-directed phosphatase). Interestingly, the upregulation of ATF4 did not lead to an increase in the levels of CHOP. Additionally, IRE1 activation was mediated by the increase in the processed form of xbp1, which would be responsible for the observed expression of edem2 and the increased levels of the chaperones GRP78 and GRP94. We were also able to detect caspase-12 proteolysis after HI or OGD. Processing of procaspase-12 was mediated by NMDA receptor and calpain activation. Moreover, our data suggest that caspase-12 activation is independent of the unfolded protein response activated by ER stress.

Towards better patient safety: WHO Surgical Safety Checklist in otorhinolaryngology.

OBJECTIVES: The World Health Organisation has developed a Surgical Safety Checklist to improve patient safety during surgery. This checklist has reduced postoperative morbidity and mortality. Prior to checklist implementation, we wanted to evaluate how it would fit into the process of otorhinolaryngology-head and neck surgery and whether it would have an impact on the awareness of safety-related issues. DESIGN: A structured questionnaire was addressed to the operating room team after consecutive operations during a 1-month period before and after checklist implementation. SETTING AND PARTICIPANTS: This study was conducted at the Department of Otorhinolaryngology at the Helsinki University Central Hospital as a part of a multicentre study. Responses were received regarding 288 operations before and 412 after checklist implementation. MAIN OUTCOME MEASURES: The questions concerned patient-related safety checks, teamwork and communication. RESULTS: The checklist improved verification of the patient's identity (P<0.001). Awareness of the patient's medical history, medication and allergies increased (P<0.001). Knowledge of the names and roles among the team members improved. The otolaryngologists and anaesthesiologists discussed possible critical events more often (P<0.001), and postoperative instructions were better recorded after use of the checklist. In addition, the checklist enhanced communication between operation team members. CONCLUSIONS: Our study confirms that the Surgical Safety Checklist fits well into the surgical working process in otorhinolaryngology-head and neck surgery improving the sharing of patient-related medical information between team members. Development of a specific checklist for otolaryngology calls for further study.

Developmental dysregulation of adult neurogenesis.

Rather than a singular event that suddenly appears during adulthood, adult neurogenesis has long been recognized as the continuation of postnatal neurogenic activity. During the first postnatal weeks, significant cellular changes occur within and adjacent to germinal matrices of the subventricular zone and dentate gyrus. The majority of granule cells are generated during this period. In addition, radial glia are transformed into astrocyte-like stem cells, the ependymal layer is formed, and the highest rates of angiogenesis, gliogenesis and myelination are observed. The first postnatal weeks are critical as the brain growth rate is maximal, and changes during this period can have a great impact on neurogenesis levels and overall brain function later in life. This review chronicles cellular changes and some of the clinically relevant dysregulations that can occur during the postnatal period, and discusses the possible impact of these changes on neurogenesis and cognitive function later in life.