Enhanced phylogenetic insights into the microbiome of chronic rhinosinusitis through the novel application of long read 16S rRNA gene amplicon sequencing.

INTRODUCTION: 16S rRNA next generation sequencing (NGS) has been the de facto standard of microbiome profiling. A limitation of this technology is the inability to accurately assign taxonomy to a species order. Long read 16S sequencing platforms, including Oxford Nanopore Technologies (ONT), have the potential to overcome this limitation. The paranasal sinuses are an ideal niche to apply this technology, being a low biomass environment where bacteria are implicated in disease propagation. Characterising the microbiome to a species order may offer new pathophysiological insights. METHODOLOGY: Cohort series comparing ONT and NGS biological conclusions. Swabs obtained endoscopically from the middle meatus of 61 CRSwNP patients underwent DNA extraction, amplification and dual sequencing (Illumina Miseq (NGS) and ONT GridION). Agreement, relative abundance, prevalence, and culture correlations were compared. RESULTS: Mean microbiome agreement between sequencers was 61.4%. Mean abundance correlations were strongest at a familial/genus order and declined at a species order where NGS lacked resolution. The most significant discrepancies applied to Corynebacterium and Cutibacterium, which were estimated in lower abundance by ONT. ONT accurately identified 84.2% of cultured species, which was significantly higher than NGS. CONCLUSIONS: ONT demonstrated superior resolution and culture correlations to NGS, but underestimated core sinonasal taxa. Future application and optimisation of this technology can advance our understanding of the sinonasal microenvironment.

Delays in referral from primary care are associated with a worse survival in patients with esophagogastric cancer.

NICE referral guidelines for suspected cancer were introduced to improve prognosis by reducing referral delays. However, over 20% of patients with esophagogastric cancer experience three or more consultations before referral. In this retrospective cohort study, we hypothesize that such a delay is associated with a worse survival compared with patients referred earlier. By utilizing Clinical Practice Research Datalink, a national primary care linked database, the first presentation, referral date, a number of consultations before referral and stage for esophagogastric cancer patients were determined. The risk of a referral after one or two consultations compared with three or more consultations was calculated for age and the presence of symptom fulfilling the NICE criteria. The risk of death according to the number of consultations before referral was determined, while accounting for stage and surgical management. 1307 patients were included. Patients referred after one (HR 0.80 95% CI 0.68-0.93 p = 0.005) or two consultations (HR 0.81 95% CI 0.67-0.98 p = 0.034) demonstrated significantly improved prognosis compared with those referred later. The risk of death was also lower for patients who underwent a resection, were younger or had an earlier stage at diagnosis. Those presenting with a symptom fulfilling the NICE criteria (OR 0.27 95% CI 0.21-0.35 p < 0.0001) were more likely to be referred earlier. This is the first study to demonstrate an association between a delay in referral and worse prognosis in esophagogastric patients. These findings should prompt further research to reduce primary care delays.

Complications after discharge and delays in adjuvant chemotherapy following colonic resection: a cohort study of linked primary and secondary care data.

AIM: By understanding the reasons for delays in adjuvant chemotherapy (AC) after colonic resection, there is the potential to improve patient outcome. The aim of this study is to determine the extent and impact of complications after hospital discharge on delays to AC. METHOD: The study cohort included patients from Hospital Episode Statistics (HES) who had a colorectal cancer resection; linkage to primary care data was provided by the Clinical Practice Research Datalink (CPRD). Complications during the index hospital stay (from HES) and after discharge (from CPRD) were compared. The risk of late AC treatment (8 weeks or later) following a complication, stoma at the index procedure or emergency admission was described after accounting for age and Charlson score. A Cox hazards model determined the association of these factors with overall survival (OS). RESULTS: A total of 1266 patients underwent AC following colon cancer resection, of whom 598 (47.2%) received treatment within 8 weeks. Patients receiving late AC had a significantly higher proportion of re-operations (7.0% vs 3.3% P < 0.005) and wound infections (5.5% vs 3.7% P = 0.042), with 96% of the latter only being noted in CPRD. In multivariate analysis, the risk of AC delay significantly increased following a complication (OR 1.53, 95% CI 1.16-2.03, P = 0.003) or a stoma at the index operation. AC delay was associated with worse OS [hazard ratio (HR) 1.44, 95% CI 1.16-1.79, P = 0.001], as was an emergency admission (HR 1.59, 95% CI 1.21-1.98, P < 0.0005). However, the presence of a complication did not independently reduce OS (HR 1.15, 95%CI 0.89-1.48, P = 0.295). CONCLUSION: The true extent and impact of complications following colonic resection is underestimated when only secondary care data are used.

Linked hospital and primary care database analysis of the impact of short-term complications on recurrence in laparoscopic inguinal hernia repair.

OBJECTIVE: To study the effects of short-term complications on recurrence following laparoscopic inguinal hernia repair using routine data. BACKGROUND: Linked primary and secondary care databases can evaluate the quality of inguinal hernia surgery by quantifying short- and long-term outcome together. METHODS: Longitudinal analysis of linked primary care (Clinical Practice Research Datalink) and hospital administrative (Hospital Episodes Statistics) databases quantified 30-day complications (wound infection and bleeding) and surgery for recurrence after primary repair performed between 1st April 1997 and 31st March 2012. RESULTS: Out of 41,545 primary inguinal hernia repairs, 10.3% (4296/41,545) were laparoscopic. Complications were less frequent following laparoscopic (1.8%, 78/4296) compared with open (3.5%, 1288/37,249) inguinal hernia repair (p < 0.05). Recurrence was more frequent following laparoscopic (3.5%, 84/2541) compared with open (1.2%, 366/31,859) repair (p < 0.05). Time to recurrence was shorter for laparoscopic (26.4 months SD 28.5) compared with open (46.7 months SD 37.6) repair (p < 0.05). Overall, complications were associated with recurrence (3.2%, 44/1366 with complications; 1.7%, 700/40,179 without complications; p < 0.05). Complications did not significantly increase the risk of recurrence in open hernia repair (OR = 1.49; 95% CI 0.97-2.30, p = 0.069). Complications following laparoscopic repair was significantly associated with increased risk of recurrence (OR = 7.86; 95% CI 3.46-17.85, p < 0.05). CONCLUSIONS: Complications recorded in linked routine data predicted recurrence following laparoscopic inguinal hernia repair. Focus must, therefore, be placed on achieving good short-term outcome, which is likely to translate to better longer term results using the laparoscopic approach.

The psychological impact of symptoms related to esophagogastric cancer resection presenting in primary care: A national linked database study.

BACKGROUND: The objective was to evaluate incidence, risk factors and impact of postoperative symptoms following esophagogastric cancer resection in primary care. METHODS: Patients undergoing esophagogastrectomy for cancer from 1998 to 2010 with linked records in Clinical Practice Research Datalink, Hospital Episodes Statistics and Office of National Statistics databases were studied. The recording of codes for reflux, dysphagia, dyspepsia, nausea, vomiting, dumping, diarrhea, steatorrhea, appetite loss, weight loss, pain and fatigue were identified up to 12 months postoperatively. Psychiatric morbidity was also examined and its risk evaluated by logistic regression analysis. RESULTS: Overall, 58.6% (1029/1755) of patients were alive 2 years after surgery. Of these, 41.1% had recorded postoperative symptoms. Reflux, dysphagia, dyspepsia and pain were more frequent following esophagectomy compared with gastrectomy (p < 0.05). Complications (OR = 1.40 95%CI 1.00-1.95) and surgical procedure predicted postoperative symptoms (p < 0.05). When compared with partial gastrectomy, esophagectomy (OR = 2.03 95%CI 1.26-3.27), total gastrectomy (OR = 2.44 95%CI 1.57-3.79) and esophagogastrectomy (OR = 2.66 95%CI 1.85-2.86) were associated with postoperative symptoms (p < 0.05). The majority of patients with postoperative psychiatric morbidity had depression or anxiety (98%). Predictors of postoperative depression/anxiety included younger age (OR = 0.97 95%CI 0.96-0.99), complications (OR = 2.40 95%CI 1.51-3.83), psychiatric history (OR = 6.73 95%CI 4.25-10.64) and postoperative symptoms (OR = 1.78 95%CI 1.17-2.71). CONCLUSIONS: Over 40% of patients had symptoms related to esophagogastric cancer resection recorded in primary care, and were associated with an increase in postoperative depression and anxiety.

[Emergence of early childhood trauma in adult psychiatric symptomatology].

Trauma comes as a result of the subject's exposure to extremely negative and stressful events, such as natural or human-provoked catastrophes, wars, serious injuries, violent deaths, tortures, terrorist attacks, rapes and other sexual crimes. A child's exposure to traumatic circumstances of this level during the crucial period of self-structuring creates rather difficult conditions for its development. Moreover, if the child does not have the opportunity to elaborate and analyze all these stressful conditions and put them into words, serious consequences, both psychological and somatic, may occur in adult life. Specific factors and child characteristics, namely, the age, the developmental stage within which the trauma occurs, its type (physical or sexual abuse, neglect or traumatic social events), frequency, duration and intensity, have been proved to seriously affect the trauma's consequences. The immediate emotional impact of trauma may include isolation, fear, feeling of weakness or loss of the sense of confidence. Moreover, mood disorders such as depression and withdrawal, negative effects on cognitive ability, language development and academic performance, difficulties in creating a secure link and post-traumatic stress disorder (PTSD) are also observed. The long-term consequences for the individual's mental health can be expressed through the following: post-traumatic stress disorder (PTSD) combined or not with depression and anxiety disorder, mood disorders, personality disorders, poor control of impulsions, dissociation disorder, psychotic disorder. Finally, apart from the dramatic impact of trauma on the person itself, there is also a high social cost to be paid as a result of the individual's poor adjustment and dysfunction in the community. Early support and intervention in the child's environment may significantly minimize the negative effects of trauma. Beyond the expression of genes, good maternal care as well as psychological support, lead to normal DNA methylation and brain development. Supporting the family and break the silence that frequently covers the traumatic events and feelings, will give the opportunity for the elaboration of all these aspects which could capture and imprison the subject in a dramatic circle of psychopathology. Moreover, the effectiveness of early interventions and child psychotherapy is now a common ground, so we have to use all our clinical instruments (dialogue, symbolic play, drawing, storytelling) in order to help the child and have the best possible result. Finally, concerning clinical practice, the emergence of early childhood trauma in adult psychiatric symptomatology is so frequent that mental health experts should take it into serious account while developing an appropriate clinical treatment for such patients.

Assessment of acute coronary syndromes: focus on novel biomarkers.

Coronary artery disease (CAD) is the leading cause of mortality in Western Societies and several developing countries. Recent evidence suggests that most detrimental clinical manifestations of CAD, such as acute coronary syndromes (ACS), are the outcome of inflammatory processes that lead to plaque formation and rupture and eventually to ischemia and potentially myocardial necrosis. Neither of the traditionally used biomarkers is thought to be the gold standard in detection of myocardial ischemia or necrosis. A biomarker that could detect quite early the ischemic myocardium as well as define the risk of a future event with high sensitivity and specificity is still lacking. Several biomarkers, implicated in the pathogenesis and clinical evolution of atherosclerosis, have emerged as potent biomarkers for early detection of myocardial ischemia. In the current review, we summarize recent evidence of the most promising biomarkers and discuss their potential role in clinical practice in patients suffering from ACSs.

Suicide and seasonality.

OBJECTIVE: Seasonal variation of deaths by suicide offers an important pathway in the study of possible suicide determinants of suicide and consequently suicide prevention. METHOD: We conducted a review of the literature on suicide seasonality, assessing articles published between 1979 and 2009. RESULTS: The majority of the studies confirm a peak in spring, mainly for men, older individuals, and violent methods of suicide. A secondary peak during autumn is observed. There is no common seasonality pattern for suicide methods. However, there are also certain studies that did not confirm seasonal variation. Inconsistent results with reduced, unchanged, and even increased suicide seasonality have been reported. Aspects on the association between seasonality and suicides are discussed. Except sex, age, and method of suicide, other parameters were taken into account to find more specific characteristics of seasonality in suicides as well. The influence of clinical, bioclimatic, sociodemographic as well as biological factors seems to affect the seasonal variation. CONCLUSION: Studies from both the Northern and the Southern hemisphere report a seasonal pattern for suicides. These studies are not only an important source of epidemiological data for suicides but also represent a global effort to uncover hidden parameters of this self-destructive behaviour.

Splenic artery aneurysm presenting with clinical features of a bleeding gastric gastrointestinal stromal tumour.

Gastrointestinal stromal tumours often present with insidious upper gastrointestinal symptoms. Initial definitive diagnosis can be difficult and therefore misdiagnosis is not infrequent. Here we report a case of upper GI bleeding caused by a splenic artery aneurysm that was misdiagnosed as a gastric GIST. This rare presentation of splenic artery aneurysm highlights the potential pitfalls of investigation in upper gastrointestinal disease.

Hospital anxiety and depression scale. A quantitative analysis in medical outpatients, psychiatric outpatients and normal subjects.

Depressive and anxiety symptomatology represent the most common psychiatric manifestations that complicate the management and prognosis of patients with somatic disorders. The Hospital Anxiety and Depression Scale (HADS) is a reliable, valid andpractical screening tool for identifying and quantifying anxiety and/or depression in non-psychiatric out patients. The aim of the present study was to compare the psychometric properties of the HADS among internal medicine outpatients, psychiatric outpatients and the generalpopulation. The present study involved 264 subjects: 95 internal medicine outpatients, 79 psychiatric outpatients and 90 normal controls. Psychiatric outpatients were diagnosed according to DSMIV-TR and inclusion criteria required the absence of any psychotic or organic psychiatric disorder. Patients with depressive disorders were divided in 3 groups: major depression, dysthymic disorderand adjustment disorder with mixed anxiety and depressed mood. All patients were administered the following psychometric tools: HADS, BDI and STAI. Subjects of the control group were administeredonly HADS. In all psychometric scales the psychiatric group presented significantly greater values than the internal medicine and the control group. In turn, the internal medicine group scoredsignificantly higher than the control group. Within the psychiatric outpatient group significantly higher HADS and HADS-D scores were observed in the major depression group followed by the dysthymicdisorder and the adjustment disorder with mixed anxiety and depressed mood group. HADS may be capable of identifying anxiety and depressive symptoms between psychiatric outpatients, internal medicine outpatients and subjects in the general population. In addition, the HADS-D subscaledifferentiates the main depressive disorders.

Quetiapine monotherapy in bipolar disorder: Two years maintenance treatment in an elderly woman.

Queatiapine has been used in bipolar mania and most recently in bipolar depression with good results. However its use in maintenance treatment has not been established yet. A case of an elderly woman suffering from bipolar disorder and diabetes mellitus (type II) is presented. The use of quetiapine as a monotherapy (300 mg/day) was efficient and safe and proved to be a good treatment in mood stabilization for two years.

Two-stage totally minimally invasive approach for acute complicated diverticulitis.

OBJECTIVES: Surgical options for acute diverticulitis with peritonitis include Hartmann's procedure or resection and primary anastomosis with or without a stoma. Initial laparoscopic lavage and drainage can control the acute intra-abdominal sepsis to allow for a delayed definitive procedure in nonemergency conditions. Potential advantages include the avoidance of a laparotomy, stoma and local infections at the origin of dehiscence and incisional hernias. We evaluated this approach in a selected group of patients. METHODS: Patients with intra-abdominal pus secondary to diverticular perforation requiring surgery were included in the study. Patients with localized pus amenable to computerized tomography (CT)-guided drainage, faecal peritonitis, severe generalized peritonitis, and those in which the perforation was spontaneously visible were excluded. Standard demographic data, CT findings, intra-operative findings and postoperative outcomes were analysed. RESULTS: Ten patients were suitable for the approach. Mean patient age was 60.2 years. Mean body mass index was 28.2 m2/kg. Mean postoperative stay was 8.5 days and uneventful in all patients. One patient re-presented after 3 weeks with acute peritonitis requiring open sigmoidectomy. Six patients successfully underwent laparoscopic sigmoidectomy with primary anastomosis 2-3 months later. Two patients were not re-operated because of comorbidity and one refused surgery. CONCLUSIONS: A two-stage totally minimally invasive approach may be a safe alternative strategy for selected cases of acute complicated diverticulitis.

Digital technologies and quality improvement in cancer surgery.

Telecommunications, multimedia and computer technologies will introduce marked changes in the management of cancer. New modalities in the representation of patient's medical records using computer technology products and services allow unlimited cross-sharing of information. Education taught through multimedia methods, and through the Internet, is available anywhere and any time just like surgical simulation, robotics and virtual reality. Thanks to computer and IT technologies, surgeons will be able to acquire, assess and validate new surgical procedures or concepts from any geographical location. Live demonstrations shared via videoconferencing facilitate mental development through the acquisition of the cognitive aspects of surgical procedures. Virtual reality is a major improvement in the processing of medical imaging. As a result, the interpretation and the simulation of therapeutic approaches to patients with cancer are facilitated through transparency, navigation and manipulation. The Internet eventually offers uninterrupted communication links between healthcare providers (teaching, training or multidisciplinary telementoring included). Computer and IT technologies will undoubtedly contribute to standardized cancer treatment modalities and determined guidelines for good clinical practice worldwide.

Abdominal wall actinomycosis associated with prolonged use of an intrauterine device: a case report and review of the literature.

The relationship between pelvic actinomycosis and the presence of an intrauterine device is well known. Abdominal wall actinomycosis with no involvement of pelvic organs in the presence of an intrauterine device is extremely rare. We report a case of a 32-year-old woman with a long-standing intrauterine device who developed abdominal wall actinomycosis. The diagnosis was established late by histopathological examination after an initial surgical procedure during which the abscess was evacuated and all the necrotic tissue was excised. Postoperatively, the patient developed two intra-abdominal abscesses, which were treated by surgical drainage. The combination of long-term high-dose antibiotic therapy with surgery led to successful management of the condition. We highlight the difficulty in diagnosis, necessity for an early postoperative diagnosis, and the importance of high-dose intravenous antibiotic therapy to prevent recurrence. Abdominal wall actinomycosis should be considered in intrauterine device users who present with abdominal abscesses of unknown origin.

[Laparoscopic splenectomy for epithelial cyst of the spleen]. / Splenectomia laparoscopica in tratamentul chistului splenic epitelial. Caz clinic.

Splenic cysts of all types are a relatively rare entity. The origin of epithelial cysts of the spleen is controversial, most probably congenital in origin. Generally, epithelial cysts of the spleen are asymptomatic and discovered incidentally. We present the case of a 40-year-old woman with a 3.5 cm splenic cyst diagnosed four years before. The cyst raised progressively in dimension, the actual size being of 6.5 cm. Computed tomography scan and magnetic resonance showed a central splenic cyst in close relations with main splenic vessels. An initial indication of partial splenectomy was established, eventually a total splenectomy being performed by laparoscopy due to close relations of the cyst with the main hilar splenic vessels. The hemostasis was assured with the aid of Ligasure Atlas 10 mm instrument. The pathology examination revealed a multilocular splenic cyst with a cuboidal epithelial lining. Central localization of splenic cysts represents an indication for total splenectomy. Laparoscopy provides a minimal access method of obtaining pathological confirmation of diagnosis, reduction of cyst complications, and a short hospital stay. This article discusses different aspects of epithelial cysts related to pathology, diagnostic and indications for operative treatment, a review of the literature being also presented.

[Cystic lymphangioma of the adrenal gland]. / Limfangiom chistic al glandei suprarenale.

Cystic lymphangioma of the adrenal gland is a rare tumor, which is often sub-clinical. Preoperative diagnosis is difficult. We present a case of a 47 year-old female in whom an incidental left cystic mass of 12 cm by 10 cm with no features of malignancy was discovered by ultrasound scan. A further computed tomography scan confirmed the ultrasound findings. Biochemical screening ruled out a secreting adrenal tumor. Because of the size of the cyst, the lesion was resected and the diagnosis of benign adrenal cystic lymphangioma was histologically confirmed. Computed tomography is the reference examination for delineating the topography and extent of the lesion, especially when it is large. Although imaging can characterize the cystic nature of a lesion, it sometimes fails to establish a specific diagnosis, so surgery or fine needle aspiration should be done for a definitive diagnosis. The characteristic features of cystic adrenal lymphangioma are discussed together with a review of the recent literature.

A difficult case of mediastinal parathyroid adenoma: theoretical and clinical considerations.

About one quarter of patients with primary hyperparathyroidism have ectopic parathyroid tissue. The majority of parathyroid glands can be reached through a cervical approach, but in about 2% of the cases the ectopic gland is in the mediastinum in a location that requires a thoracic approach. Failure to remove ectopic mediastinal parathyroid tissue results in persistent hyperparathyroidism. Reoperative exploration for persistent hyperparathyroidism is often difficult even in the hands of experienced surgeons. Recent advances in preoperative localization techniques and intraoperative parathyroid hormone measurement have improved the rates of successful resection. We present a difficult case of persistent hyperparathyroidism secondary to an ectopic middle mediastinal parathyroid adenoma, which was eventually successfully managed in a specialised unit.

Distinct antigenic features of linear epitopes at the N-terminus and C-terminus of 65 kDa glutamic acid decarboxylase (GAD65): implications for autoantigen modification during pathogenesis.

Autoantibodies to 65 kDa glutamic acid decarboxylase (GAD65) are produced in many patients with autoimmune polyendocrine syndrome type II (APS-II) or stiff-man syndrome (SMS) and are heterogeneous in their epitope specificities, recognizing both conformational and linear determinants. Major linear epitopes of GAD, which are recognized by autoantibodies in a minority of these patients, occur in the N-terminal and C-terminal regions. We have investigated antibody recognition of the N- and C-termini of GAD65 in relation to their structural features as an approach to understanding what modifications to the native GAD structure may occur that facilitate the generation of antibodies specific to linear epitopes in these regions during the autoimmune pathogenesis. A monoclonal antibody specific to the N-terminus of GAD65 bound both native and denatured GAD in ELISA, whereas monoclonal and polyclonal antibodies specific to the C-terminus of GAD bound only denatured GAD. These antibodies were epitope mapped using random peptide phage-display libraries and the epitopes related to a previously proposed structural model of GAD65. This has led us to propose that the alpha-helical secondary structure of the C-terminus of GAD65 must be denatured to generate linear epitopes. In contrast, the N-terminus is both surface exposed and linear in the native structure, but may be masked by membrane interactions, which must be broken to facilitate recognition by B cells.