Characterization of a Novel Chimeric Swine Enteric Coronavirus from Diseased Pigs in Central Eastern Europe in 2016

During a severe outbreak of diarrhoea and vomiting in a pig herd in Central Eastern Europe, faecal samples were tested positive for porcine epidemic diarrhoea virus (PEDV) and negative for transmissible gastroenteritis virus (TGEV) using a commercial RT‐qPCR assay that can detect both of these coronaviruses. However, further analyses, using other TGEV‐ and PEDV‐specific RT‐qPCR assays, provided results inconsistent with infection by either of these viruses. Sequencing of an amplicon (ca. 1.6 kb), generated by an RT‐PCR specific for the PEDV S‐gene, indicated a very close similarity (ca. 99% identity) to recently described chimeric viruses termed swine enteric coronaviruses (SeCoVs). These viruses (with an RNA genome of ca. 28 kb) were first identified in Italy in samples from 2009 but have not been detected there since 2012. A closely related virus was detected in archived samples in Germany from 2012, but has not been detected subsequently. Building on the initial sequence data, further amplicons were generated and over 9 kb of sequence corresponding to the 3′‐terminus of the new SeCoV genome was determined. Sequence comparisons showed that the three known SeCoVs are ≥98% identical across this region and contain the S‐gene and 3a sequences from PEDV within a backbone of TGEV, but the viruses are clearly distinct from each other. It is demonstrated, for the first time, that pigs from within the SeCoV‐infected herd seroconverted against PEDV but tested negative in a TGEV‐specific ELISA that detects antibodies against the S protein. These results indicate that SeCoV is continuing to circulate in Europe and suggest it can cause a disease that is very similar to PED. Specific detection of the chimeric SeCoVs either requires development of a new diagnostic RT‐qPCR assay or the combined use of assays targeting the PEDV S‐gene and another part of the TGEV genome.     

Why are patients still in hospital after fast-track,unilateral unicompartmental knee arthroplasty

Background and purpose — Previous studies have investigated risk factors related to prolonged length of stay following total knee arthroplasty (TKA), but little is known about specific factors resulting in continued hospitalization within the 1st postoperative days after unicompartmental knee arthroplasty (UKA). We investigated what specific factors prevent patients from being discharged on the day of surgery (DOS) and the first postoperative day (POD-1) following primary UKA in a fast-track setting.Patients and methods — We prospectively collected data on 100 consecutive and unselected medial UKA patients operated from December 2017 to May 2019. All patients were operated in a standardized fast-track setup with functional discharge criteria continuously evaluated from DOS and until discharge.Results — Median length of stay for the entire cohort was 1 day. 22% and 78% of all patients were discharged on DOS and POD-1, respectively. Lack of mobilization and pain separately delayed discharge in respectively 78% and 24% of patients on DOS. The main reasons for lack of mobilization were motor blockade (37%) and logistical factors (26%). For patients placed 1st or 2nd on the operating list, we estimate that the same-day discharge rate would increase to 55% and 40% respectively, assuming that pain and mobilization were successfully managed.Interpretation — One-fifth of unselected UKA patients operated in a standardized fast-track setup were discharged on DOS. Pain and lack of mobilization were the major reasons for continued hospitalization within the initial postoperative 24–48 hours. Strategies aimed at decreasing length of stay after UKA should strive to improve analgesia and postoperative mobilization.

The number of unicompartmental knee arthroplasties (UKAs) performed in patients suffering from osteoarthritis has steadily increased. UKA has the potential benefit of not only improving patient-reported outcomes, but also to reduce morbidity, complications, and cost (Liddle et al. 2014, Beard et al. 2019). In the United Kingdom, 9% of all primary knee arthroplasties performed in 2018 were UKAs while this number is as high as 20% in Denmark (Danish Knee Arthroplasty Register 2019, National Joint Registry for England 2019).UKA is effective and safe when performed in a fast-track setting and outpatient UKA in selected patients has been shown to be feasible and safe (Munk et al. 2012, Cross and Berger 2014, Bovonratwet et al. 2017, Kort et al. 2017). However, the number of patients actually being discharged on DOS that were scheduled for outpatient surgery differs between studies and ranges from 37% to 100% (Gondusky et al. 2014, Bradley et al. 2017, Jenkins et al. 2019, Rytter et al. 2019).Studies have shown an association between increased length of stay (LOS) and an increase in both complication and readmission rates (Otero et al. 2016). In order to reduce LOS and increase patient satisfaction, a focus on successfully managing well-defined discharge criteria in a multimodal approach is imperative (Husted et al. 2008, Cross and Berger 2014). In addition, decreased LOS and outpatient procedures are associated with financial benefits, which have further fueled interest in decreasing LOS and ensuring DOS discharged following UKA (Bradley et al. 2017). Finally, decreased LOS is also shown to increase patient satisfaction levels (Reilly et al. 2005, Richter and Diduch 2017).A study has been conducted to explore reasons for prolonged hospitalization in a fast-track setting following TKA (Husted et al. 2011). However, in spite of a growing number of UKAs performed each year, no study explicitly exploring reasons for prolonged hospitalization beyond DOS following UKA in a fast-track setting has been published at present.Therefore, we investigated reasons for continued hospitalization beyond DOS following UKA in a fast-track setting.     

Cervical Spine Clearance in Trauma Patients with an Unreliable Physical Examination

Background

The objective of this study was to describe and compare the timing of cervical spine clearance in trauma patients with an unreliable physical examination.

Methods

We prospectively included adult trauma patients admitted with a cervical collar and an unreliable clinical examination (as defined by the NEXUS criteria) at two level 1 trauma centers: one in the USA (US) and one in Denmark (DK). We excluded patients with cervical spine injuries requiring a collar or surgery as treatment and patients with a collar placed after hospital arrival. The primary outcome was time from emergency department (ED) arrival to collar removal. Secondary outcomes included time to CT of the cervical spine (CTCS). At the US trauma center, an institutional protocol allowing cervical spine clearance exclusively by CTCS was in place. At the Danish trauma center, cervical spine clearance was based on a clinical evaluation by an orthopedic surgeon, usually after CTCS.

Results

A total of 113 patients were included (US: n = 56; DK: n = 57). The median age was 47 years, and 68% were males. The main reasons for an unreliable physical examination were a Glasgow Coma Scale score below 14 (35%), distracting injuries (26%), cervical spine tenderness (13%) and intoxication (13%). The injury severity score at the US trauma center was higher than at the DK trauma center (median: 17 vs. 11, p = 0.03). Both time to CTCS (median: 41 vs. 18 min, p < 0.0001) and time to collar removal (median: 1042 vs. 49 min, p < 0.0001) were significantly greater at the US trauma center.

Conclusions

Time to collar removal was significantly greater in a trauma center utilizing a cervical spine clearance protocol based on CTCS. As patients may develop complications related to the collar, future studies should clarify how early removal can be implemented without increasing the risk of morbidity.

     

Massive infection and loss of CD4+ T cells occurs in the intestinal tract of neonatal rhesus macaques in acute SIV infection

Rapid, profound, and selective depletion of memory CD4+ T cells has now been confirmed to occur in simian immunodeficiency virus (SIV)-infected adult macaques and human immunodeficiency virus (HIV)-infected humans. Within days of infection, marked depletion of memory CD4+ T cells occurs primarily in mucosal tissues, the major reservoir for memory CD4+ T cells in adults. However, HIV infection in neonates often results in higher viral loads and rapid disease progression, despite the paucity of memory CD4+ T cells in the peripheral blood. Here, we examined the immunophenotype of CD4+ T cells in normal and SIV-infected neonatal macaques to determine the distribution of naive and memory T-cell subsets in tissues. We demonstrate that, similar to adults, neonates have abundant memory CD4+ T cells in the intestinal tract and spleen and that these are selectively infected and depleted in primary SIV infection. Within 12 days of SIV infection, activated (CD69+), central memory (CD95+CD28+) CD4+ T cells are marked and persistently depleted in the intestine and other tissues of neonates compared with controls. The results in dicate that "activated" central memory CD4+ T cells are the major target for early SIV infection and CD4+ T cell depletion in neonatal macaques.     

Severity of postoperative hypophosphatemia in relation to glucose administration and renal handling of phosphate

Major surgery is associated with fall in the concentration of inorganic phosphate in serum, as is intravenous infusion of glucose. Hypophosphatemia during different forms of postoperative dextrose administration was evaluated in patients who had undergone colorectal surgery. They were randomized to two groups. All patients received standardized intravenous fluids on the first 3 postoperative days, but one group had constant infusion of a solution containing glucose (4%), sodium (40 mmol/l) and potassium (20 mmol/l) throughout the observation period, while the other group had a 5-hour infusion of 10% glucose daily, with potassium and sodium solution in between. The amounts of administered glucose and electrolytes were the same in both groups. The serum phosphate levels were significantly lower in the group with constant glucose infusion, due to intergroup difference in renal handling of phosphate. Significantly less phosphate was reabsorbed in the proximal tubules when glucose was given as 24-hour infusion than in the group with 5-hour infusion.     

An outbreak of legionnaires disease caused by long-distance spread from an industrial air scrubber in Sarpsborg, Norway.

BACKGROUND: On 21 May 2005, the Norwegian health authorities were alerted by officials from a local hospital that several recent patients had received the diagnosis of legionnaires disease; all patients resided in 2 neighboring municipalities. We investigated the outbreak to identify the source and to implement control measures. METHODS: We interviewed all surviving case patients and investigated and harvested samples from 23 businesses with cooling towers and other potential infection sources. The locations of the businesses and the patients' residences and movements were mapped. We calculated attack rates and risk ratios among people living within various radii of each potential source. Isolates of Legionella pneumophila were compared using molecular methods. RESULTS: Among 56 case patients, 10 died. The case patients became ill 12-25 May, resided up to 20 km apart, and had not visited places in common. Those living up to 1 km from a particular air scrubber had the highest risk ratio, and only for this source did the risk ratio decrease as the radius widened. Genetically identical L. pneumophila serogroup 1 isolates were recovered from patients and the air scrubber. The air scrubber is an industrial pollution-control device that cleans air for dust particles by spraying with water. The circulating water had a high organic content, pH of 8-9, and temperature of 40 degrees C. The air was expelled at 20 m/s and contained a high amount of aerosolized water. CONCLUSIONS: The high velocity, large drift, and high humidity in the air scrubber may have contributed to the wide spread of Legionella species, probably for >10 km. The risk of Legionella spread from air scrubbers should be assessed.     

Severe hypoglycaemia in 1076 adult patients with type 1 diabetes: influence of risk markers and selection

BACKGROUND: Differences between studies in rates of severe hypoglycaemia in type 1 diabetic cohorts are common and poorly understood. The purpose of this study was to assess the frequency of severe hypoglycaemia in unselected patients treated in different secondary care centres and to evaluate the influence of risk markers, clinical setting and selection. METHODS: Cross-sectional Danish-British multicentre survey of 1076 consecutive adult patients with clinical type 1 diabetes who completed a detailed questionnaire on hypoglycaemia and related issues. Key variable was the self-reported rate of severe hypoglycaemia during the preceding year. RESULTS: The overall rate of severe hypoglycaemia in the preceding year was 1.3 episodes/patient-year and episodes were reported by 36.7% of subjects. The distribution was highly skewed with 5% of subjects accounting for 54% of all episodes. There were no significant differences between countries or centres. Reduced hypoglycaemia awareness, peripheral neuropathy and smoking were the only significant risk markers of severe hypoglycaemia in a stepwise multivariate analysis. In a subgroup selected to be similar to the Diabetes Control and Complications Trial (DCCT) cohort, the rate of severe hypoglycaemia was 0.35 episodes/patient-year and only retinopathy was a significant risk marker together with state of awareness. CONCLUSION: Severe hypoglycaemia remains a significant clinical problem in type 1 diabetes. The rate of severe hypoglycaemia and the influence of risk markers are very sensitive to selection and differences in rates between centres or studies seem to disappear after correction for differences in clinical characteristics. Smoking is a novel overall risk marker of severe hypoglycaemia.     

Spontaneous and induced immunoglobulin synthesis and anti-neutrophil cytoplasm antibodies in Wegener's granulomatosis: relation to leukocyte subpopulations in blood and active lesions

Summary Using a reverse plaque forming cell (PFC) assay the production of immunoglobulin (Ig) by peripheral blood mononuclear cells (MNCs) in vitro was studied in 12 patients with Wegener's granulomatosis (WG). Spontaneous IgG production was increased in two of six untreated patients. The IgG response of MNCs from eight untreated patients to pokeweed mitogen (PWM) and Epstein-Barr virus (EBV) stimulation was significantly depressed. The IgM and IgA production followed the individual pattern of IgG. Blood B-cell and T-cell subset concentrations were normal before therapy, whereas the monocyte concentration was increased in four of six patients. Titers of anti-neutrophil cytoplasm autoantibodies (ANCAs) did not correlate with spontaneous or induced Ig production nor with blood leukocyte subset concentrations. Biopsy specimens from upper respiratory tract lesions in seven untreated patients showed numerous macrophages, activated T lymphocytes, and plasma cells, suggesting a pathogenetic role of these cells in the development of lesions and local production of ANCAs.     

Signal‐Averaged P Wave Duration and the Dimensions of the Atria

Background: Delay of atrial electrical conduction measured as prolonged signal‐averaged P wave duration (SAPWD) could be due to atrial enlargement. Here, we aimed to compare different atrial size parameters obtained from echocardiography with the SAPWD measured with a signal‐averaged electrocardiogram (SAECG). Methods: In 74 patients scheduled for elective echocardiography, an SAECG was recorded directly after the echocardiogram. We measured the SAPWD and registered clinical characteristics. The correlation between the SAPWD and the left atrial diameter (LAD), left atrial volume (LAV), right atrial volume (RAV), and total atrial volume (TAV) was analyzed by linear regression analyses. The effect of concomitant risk factors on TAV and the SAPWD was examined. Results: Linear regression analysis showed that the correlation between the SAPWD and the LAD was significant (R²= 0.11, P = 0.03). However, LAV (R²= 0.15, P = 0.009), RAV (R²= 0.27, P = 0.0003), and TAV (R²= 0.37, P < 0.0001) were more strongly correlated to the SAPWD. The TAV and the SAPWD were not significantly associated with coexisting risk factors. Conclusions: The SAPWD is significantly correlated to the atrial size; most strongly to the TAV. The size of the right atrium, with the sinus node area, appears to affect the SAPWD.