External validation of the Oldham composite Covid-19 associated mortality model (OCCAM), a prognostic model for death in patients hospitalised with Covid-19.

OBJECTIVE: External validation of the Oldham Composite Covid-19 associated Mortality Model (OCCAM), a prognostic model for Covid-19 mortality in hospitalised patients comprised of age, history of hypertension, current or previous malignancy, admission platelet count < 150 × 103/µL, admission CRP ≥ 100 µg/mL, acute kidney injury (AKI), and radiographic evidence of > 50% total lung field infiltrates. PATIENTS AND METHODS: Retrospective study assessing discrimination (c-statistic) and calibration of OCCAM for death in hospital or within 30 days of discharge. 300 adults admitted to six district general and teaching hospitals in North West England for treatment of Covid-19 between September 2020 and February 2021 were included. RESULTS: Two hundred and ninety-seven patients were included in the validation cohort analysis, with a mortality rate of 32.8%. The c-statistic was 0.794 (95% confidence interval 0.742-0.847) vs. 0.805 (95% confidence interval 0.766 - 0.844) in the development cohort. Visual inspection of calibration plots demonstrate excellent calibration across risk groups, with a calibration slope for the external validation cohort of 0.963. CONCLUSION: The OCCAM model is an effective prognostic tool that can be utilised at the time of initial patient assessment to aid decisions around admission and discharge, use of therapeutics, and shared decision-making with patients. Clinicians should remain aware of the need for ongoing validation of all Covid-19 prognostic models in light of changes in host immunity and emerging variants.

Osteoporosis is a novel risk factor of infections and sepsis: A cohort study.

Background: Accumulating evidence suggests the interaction of bone metabolism and the immune system, but how bone health is associated with the risk of infections remains unknown. Methods: This study aimed to investigate the relationship of bone mineral density (BMD) with the risk of common infections and sepsis in Hong Kong Osteoporosis Study (HKOS). A prospective cohort study, initiated in 1995 and followed until 31 December 2020, of 5,717 participants examined the association of BMD at three skeletal sites (lumbar spine, femoral neck, and total hip) with common infections - pneumonia, urinary tract infection (UTI), skin infection, and sepsis. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Findings: During the median follow-up of 17 years, higher BMD T-scores at the femoral neck and total hip were significantly associated with the reduced risk of pneumonia (HRs 0.89 and 0.87; 95% CIs 0.82 to 0.98 and 0.81 to 0.95), UTI (HRs 0.85 and 0.86; 95% CIs 0.76 to 0.94 and 0.78 to 0.95), skin infection (HRs 0.85 and 0.82; 95% CIs 0.74 to 0.97 and 0.73 to 0.93), and sepsis (HRs 0.83 and 0.82; 95% CIs 0.71 to 0.97 and 0.72 to 0.94). A significant association was observed for the lumbar spine BMD T-score with the risk of skin infection (HR 0.86; 95% CI: 0.78 to 0.95) but not with other infections and sepsis. Similarly, participants with osteoporosis, but not osteopenia, were significantly associated with an increased risk of infections and sepsis compared to those with normal BMD. Interpretation: BMD is a novel risk factor of infections and sepsis. People with low BMD, particularly those with osteoporosis, are at higher risk of infections and sepsis than those with normal BMD. Further studies on whether improving bone health can reduce the risk of infections and sepsis are warranted. Funding: None.

Predictive factors, preventive implications, and personalized surgical strategies for bone metastasis from lung cancer: population-based approach with a comprehensive cancer center-based study.

Background: Bone metastasis (BM) and skeletal-related events (SREs) happen to advanced lung cancer (LC) patients without warning. LC-BM patients are often passive to BM diagnosis and surgical treatment. It is necessary to guide the diagnosis and treatment paradigm for LC-BM patients from reactive medicine toward predictive, preventive, and personalized medicine (PPPM) step by step. Methods: Two independent study cohorts including LC-BM patients were analyzed, including the Surveillance, Epidemiology, and End Results (SEER) cohort (n = 203942) and the prospective Fudan University Shanghai Cancer Center (FUSCC) cohort (n = 59). The epidemiological trends of BM in LC patients were depicted. Risk factors for BM were identified using a multivariable logistic regression model. An individualized nomogram was developed for BM risk stratification. Personalized surgical strategies and perioperative care were described for FUSCC cohort. Results: The BM incidence rate in LC patients grew (from 17.53% in 2010 to 19.05% in 2016). Liver metastasis was a significant risk factor for BM (OR = 4.53, 95% CI = 4.38-4.69) and poor prognosis (HR = 1.29, 95% CI = 1.25-1.32). The individualized nomogram exhibited good predictive performance for BM risk stratification (AUC = 0.784, 95%CI = 0.781-0.786). Younger patients, males, patients with high invasive LC, and patients with other distant site metastases should be prioritized for BM prevention. Spine is the most common site of BM, causing back pain (91.5%), pathological vertebral fracture (27.1%), and difficult walking (25.4%). Spinal surgery with personalized spinal reconstruction significantly relieved pain and improved daily activities. Perioperative inflammation, immune, and nutrition abnormities warrant personalized managements. Radiotherapy needs to be recommended for specific postoperative individuals. Conclusions: The presence of liver metastasis is a strong predictor of LC-BM. It is recommended to take proactive measures to prevent BM and its SREs, particularly in young patients, males, high invasive LC, and LC with liver metastasis. BM surgery and perioperative management are personalized and required. In addition, adjuvant radiation following separation surgery must also be included in PPPM-guided management. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-022-00270-9.

Patient characteristics and predictors of mortality in 470 adults admitted to a district general hospital in England with Covid-19.

Understanding risk factors for death from Covid-19 is key to providing good quality clinical care. We assessed the presenting characteristics of the 'first wave' of patients with Covid-19 at Royal Oldham Hospital, UK and undertook logistic regression modelling to investigate factors associated with death. Of 470 patients admitted, 169 (36%) died. The median age was 71 years (interquartile range 57-82), and 255 (54.3%) were men. The most common comorbidities were hypertension (n = 218, 46.4%), diabetes (n = 143, 30.4%) and chronic neurological disease (n = 123, 26.1%). The most frequent complications were acute kidney injury (AKI) (n = 157, 33.4%) and myocardial injury (n = 21, 4.5%). Forty-three (9.1%) patients required intubation and ventilation, and 39 (8.3%) received non-invasive ventilation. Independent risk factors for death were increasing age (odds ratio (OR) per 10 year increase above 40 years 1.87, 95% confidence interval (CI) 1.57-2.27), hypertension (OR 1.72, 95% CI 1.10-2.70), cancer (OR 2.20, 95% CI 1.27-3.81), platelets <150 × 103/µl (OR 1.93, 95% CI 1.13-3.30), C-reactive protein ≥100 µg/ml (OR 1.68, 95% CI 1.05-2.68), >50% chest radiograph infiltrates (OR 2.09, 95% CI 1.16-3.77) and AKI (OR 2.60, 95% CI 1.64-4.13). There was no independent association between death and gender, ethnicity, deprivation level, fever, SpO2/FiO2, lymphopoenia or other comorbidities. These findings will inform clinical and shared decision making, including use of respiratory support and therapeutic agents.

Patient characteristics and predictors of mortality in 470 adults admitted to a district general hospital in England with Covid-19

BackgroundUnderstanding risk factors for death in Covid-19 is key to providing good quality clinical care. Due to a paucity of robust evidence, we sought to assess the presenting characteristics of patients with Covid-19 and investigate factors associated with death. MethodsRetrospective analysis of adults admitted with Covid-19 to Royal Oldham Hospital, UK. Logistic regression modelling was utilised to explore factors predicting death. Results470 patients were admitted, of whom 169 (36%) died. The median age was 71 years (IQR 57-82), and 255 (54.3%) were men. The most common comorbidities were hypertension (n=218, 46.4%), diabetes (n=143, 30.4%) and chronic neurological disease (n=123, 26.1%). The most frequent complications were acute kidney injury (n=157, 33.4%) and myocardial injury (n=21, 4.5%). Forty-three (9.1%) patients required intubation and ventilation, and 39 (8.3%) received non-invasive ventilation Independent risk factors for death were increasing age (OR per 10 year increase above 40 years 1.87, 95% CI 1.57-2.27), hypertension (OR 1.72, 1.10-2.70), cancer (OR 2.20, 1.27-3.81), platelets <150x103/{micro}L (OR 1.93, 1.13-3.30), C-reactive protein [≥]100 {micro}g/mL (OR 1.68, 1.05-2.68), >50% chest radiograph infiltrates, (OR 2.09, 1.16-3.77) and acute kidney injury (OR 2.60, 1.64-4.13). There was no independent association between death and gender, ethnicity, deprivation level, fever, SpO2/FiO2 (oxygen saturation index), lymphopenia or other comorbidities. ConclusionsWe characterised the first wave of patients with Covid-19 in one of Englands highest incidence areas, determining which factors predict death. These findings will inform clinical and shared decision making, including the use of respiratory support and therapeutic agents. SummaryIncreasing age, hypertension, cancer, platelets <150x103/{micro}L, CRP[≥]100 {micro}g/mL, >50% chest radiograph infiltrates, and acute kidney injury predict in-hospital death from Covid-19, whilst gender, ethnicity, deprivation level, fever, SpO2/FiO2 (oxygen saturation index), lymphopenia and other comorbidities do not.

Quantitative profiling of regional protein expression in rat retina after partial optic nerve transection using fluorescence difference two­dimensional gel electrophoresis.

To examine the difference between primary and secondary retinal ganglion cell (RGC) degeneration, the protein expression at four regions of retina including superior, temporal, inferior and nasal quadrant in a rat model of partial optic nerve transection (pONT) using 2­D Fluorescence Difference Gel Electrophoresis (DIGE) were investigated. Unilateral pONT was performed on the temporal side of optic nerves of adult Wistar rats to separate primary and secondary RGC loss. Topographical quantification of RGCs labeled by Rbpms antibody and analysis of axonal injury by grading of optic nerve damage at 1 week (n=8) and 8 weeks (n=15) after pONT demonstrated early RGC loss at temporal region, which is considered as primary RGC degeneration and progressing RGC loss at nasal region, which is considered as secondary RGC degeneration. Early protein expression in each retinal quadrant (n=4) at 2 weeks after pONT was compared with the corresponding quadrant in the contralateral control eye by DIGE. For all comparisons, 24 differentially expressed proteins (>1.2­fold; P<0.05; ≥3 non­duplicated peptide matches) were identified by mass spectrometry (MS). Interestingly, in the nasal retina, serum albumin and members of crystallin family, including αA, αB, ßA2, ßA3, ßB2 and gamma S indicating stress response were upregulated. By contrast, only αB and ßA2 crystallin proteins were altered in temporal quadrant. In the superior and inferior quadrants, ßB2 crystallin, keratin type I, S­arrestin and lamin­B1 were upregulated, while heat shock cognate 71 kDa protein and heterogeneous nuclear ribonucleoproteins A2/B1 were downregulated. In summary, the use of DIGE followed by MS is useful to detect early regional protein regulation in the retina after localized optic nerve injury.

Encapsulation of Perovskite Solar Cells for High Humidity Conditions.

We examined different encapsulation strategies for perovskite solar cells by testing the device stability under continuous illumination, elevated temperature (85 °C) and ambient humidity of 65 %. The effects of the use of different epoxies, protective layers and the presence of desiccant were investigated. The best stability (retention of ∼80 % of initial efficiency on average after 48 h) was obtained for devices protected by a SiO2 film and encapsulated with a UV-curable epoxy including a desiccant sheet. However, the stability of ZnO-based cells encapsulated by the same method was found to be inferior to that of TiO2 -based cells. Finally, outdoor performance tests were performed for TiO2 -based cells (30-90 % ambient humidity). All the stability tests were performed following the established international summit on organic photovoltaic stability (ISOS) protocols for organic solar cell testing (ISOS-L2 and ISOS-O1).

Travelling wave solutions of the reaction-diffusion mathematical model of glioblastoma growth: an Abel equation based approach.

We consider quasi-stationary (travelling wave type) solutions to a nonlinear reaction-diffusion equation with arbitrary, autonomous coefficients, describing the evolution of glioblastomas, aggressive primary brain tumors that are characterized by extensive infiltration into the brain and are highly resistant to treatment. The second order nonlinear equation describing the glioblastoma growth through travelling waves can be reduced to a first order Abel type equation. By using the integrability conditions for the Abel equation several classes of exact travelling wave solutions of the general reaction-diffusion equation that describes glioblastoma growth are obtained, corresponding to different forms of the product of the diffusion and reaction functions. The solutions are obtained by using the Chiellini lemma and the Lemke transformation, respectively, and the corresponding equations represent generalizations of the classical Fisher-Kolmogorov equation. The biological implications of two classes of solutions are also investigated by using both numerical and semi-analytical methods for realistic values of the biological parameters.

Dyspnea-12 is a valid and reliable measure of breathlessness in patients with interstitial lung disease.

OBJECTIVE: In this study, we aimed to determine the validity and reliability of the Dyspnea-12 questionnaire (D-12) for the assessment of breathlessness in patients with interstitial lung disease (ILD). METHODS: A total of 101 patients with ILD completed the D-12 (scale range, 0-36, with a high score indicating worse dyspnea), Medical Research Council (MRC) dyspnea scale, St. George Respiratory Questionnaire (SGRQ), and Hospital Anxiety and Depression Scale (HADS) at baseline, and 84 patients completed the D-12 and a global health transition score at follow-up 2 weeks later. D-12 psychometric properties, including floor and ceiling effects, internal consistency, test-retest reliability, and construct validity were examined. RESULTS: The D-12 showed good internal consistency (Cronbach α, 0.93) and repeatability (intraclass correlation coefficient, 0.94). Its scores were significantly associated with MRC grade (r = 0.59; P < .001), SGRQ (symptoms, r = 0.57; activities, r = 0.78; impacts, r = 0.75; total, r = 0.79; P < .001). Factor analysis confirmed the previously determined structure of the D-12 in this patient group. CONCLUSION: In patients with ILD, the D-12, a patient-reported measure of dyspnea severity that requires no reference to activity, is a reliable and valid instrument. It is short, simple to complete, and easy to score.

Radiofrequency ablation of recurrent fibromatosis.

Radiofrequency (RF) ablation has received increasing attention as a promising technique for treating focal malignant disease and is a safe and effective technique for tumor control. The authors report a case in which RF ablation was performed in a woman with recurrent fibromatosis of the lower back who refused further surgery. Satisfactory results were obtained at long-term follow-up, with no recurrence of tumor.

The flexion-extension profile of lumbar spine in 100 healthy volunteers.

STUDY DESIGN: Dynamic lumbar flexion-extension motions were assessed by an electrogoniometer and a videofluoroscopy unit simultaneously. OBJECTIVES: The aims of this study were to assess the motion profile of lumbar spine in different genders and age groups and to assess their differences. SUMMARY OF BACKGROUNDS DATA: The dynamic lumbar flexion-extension motions analysis method has been developed and validated. However, data profile of the spinal motions of healthy volunteers has not been established. METHODS.: A total of 100 healthy volunteers, including 50 men and 50 women, were recruited. They were then divided into four equal groups, following their age ranges of 21 to 30 years, 31 to 40 years, 41 to 50 years, and 51 years and older. Lumbar flexion-extension motion was assessed with an electrogoniometer and videofluoroscopy simultaneously. Radiologic images of the lumbar spine were captured during flexion-extension in 10 degrees intervals. Intervertebral flexion-extension (IVFE) of each vertebral level was calculated. The spinal motion of different genders was compared segment by segment with independent t test. The spinal motion of different age groups was compared with one-way analysis of variance. RESULTS: A linear-liked pattern of the IVFE curves was observed in different genders and age groups. No statistically significant difference in the pattern of motion was found between genders. However, statistically significant difference in the slope of IVFE curves was found at all lumbar levels in subjects whose age was 51 years or older (P < 0.05). CONCLUSIONS: Assessment of motion profile was found to be helpful for the identification of spinal disorders in clinical practice. Because of the normal variation of spinal motion of subjects in different age ranges, interpretation of spinal motion disorders should be careful. Although the sample size in this study was limited, the database generated might be useful to assist the diagnosis of spinal "instability" in the future.

Randomized controlled trial to compare the dose of adjuvant chemotherapy after curative resection of hepatocellular carcinoma.

BACKGROUND AND AIM: Adjuvant locoregional chemotherapy has been shown to be useful to prevent recurrence after curative resection of hepatocellular carcinoma (HCC) in some retrospective studies. Our aim was to compare the dose effect in the prevention of tumor recurrence. METHODS: A prospective randomized controlled trial was conducted in patients with curative resection of HCC; they were given either one intra-arterial dose of cisplatin/lipiodol, or received four doses, once every 3 months. The rates of recurrence, disease-free and overall survival were compared. RESULTS: During a median follow up of 818 days, 21 patients received one dose and 19 received four doses, with 10 (47.6%) and eight (42.1%) recurrences, respectively. The 1-year, 2-year and 3-year disease-free survival rates were 71%, 54% and 44% for the one-dose group and 74%, 60% and 40% for the four-dose group (P = 0.78). The respective overall survival rates were 85%, 74%, 55% and 84%, 71%, 40% (P = 0.64). The only prognostic factor was presence of vascular permeation. The side-effects were mild and tolerable. CONCLUSIONS: There is no significant difference in the survival rates between the two groups. Adjuvant chemotherapy may not be useful.

Diagnostic and treatment behaviour in children with chronic respiratory symptoms: relationship with socioeconomic factors.

BACKGROUND: The prevalence and severity of asthma is believed to increase with increasing socioeconomic deprivation. The relationship between asthma diagnosis, symptoms, diagnostic accuracy, and socioeconomic deprivation as determined by Townsend scores was determined in Sheffield schoolchildren. METHODS: All 6021 schoolchildren aged 8-9 years in one school year in Sheffield were given a parent respondent survey based on International Survey of Asthma and Allergies in Childhood (ISAAC) questions. RESULTS: 5011/6021 (83.2%) questionnaires were returned. Postcode data were available in 4131 replies (82.4%) and were used to assign a composite deprivation score (Townsend score). Scores were divided into five quintiles, with group 1 being least and group 5 being most deprived. A positive trend was observed from group 1 to group 5 for the prevalence of wheeze in the previous 12 months, wheeze attacks >or=4/year, nocturnal wheeze and cough (all p<0.001), cough and/or wheeze "most times" with exertion (p<0.03), current asthma (p<0.001), and significant asthma symptoms (p<0.001). No significant trend was observed for lifetime wheeze or attacks of speech limiting wheeze. There were no significant trends in the prevalence of current asthmatic children without significant symptoms (overdiagnosis) or children with significant asthma symptoms but no current asthma diagnosis (underdiagnosis) across the social groups. There was a significant negative trend in the ratio of asthma medication to asthma diagnosis from least to most deprived groups (p<0.001). CONCLUSIONS: Asthma morbidity and severity increase according to the level of socioeconomic deprivation. This may be due to differences in environment, asthma management, and/or symptom reporting. Diagnostic accuracy does not vary significantly across deprivation groups but children living in areas of least deprivation and taking asthma medication are less likely to be labelled as having asthma, suggesting diagnostic labelling bias.

Development and validation of a new technique for assessing lumbar spine motion.

STUDY DESIGN: Dynamic lumbar flexion-extension motions were assessed by an electrogoniometer and a videofluoroscopy unit simultaneously. OBJECTIVE: To develop and validate a new technique for the assessment of lumbar spine motion. SUMMARY OF BACKGROUND DATA: Spine instability, a clinical condition that is common but difficult to diagnose, has been suggested to involve a characteristic change in the relation between vertebrae during motion. Assessment of lumbar instability using functional radiographs is controversial. Information regarding dynamic spine kinematics in vivo is limited. METHODS: A lumbar spine motion analysis system was developed, and its reliability was assessed. Simultaneous total flexion range of motion and segmental motion of the lumbar spine were assessed in 30 healthy volunteers. Lumbar images were captured in 10 degrees intervals during flexion-extension. Intervertebral flexion-extension of each vertebral level was calculated. RESULTS: In flexion, the lumbar vertebrae flexed with a descending order from L1 to L5 throughout the motion. Conversely, the concavity of lumbar lordosis increased steadily in extension. No statistically significant difference in the pattern of motion was found between genders. CONCLUSIONS: The results from this study showed that the newly developed technique is reliable. It may have potential value for evaluating spine instability in clinical practice.

Increasing prevalence of asthma diagnosis and symptoms in children is confined to mild symptoms.

BACKGROUND: The prevalence of childhood asthma is increasing but few studies have investigated trends in asthma severity. We investigated trends in asthma diagnosis and symptom morbidity between an eight year time period in a paired prevalence study. METHODS: All children in one single school year aged 8-9 years in the city of Sheffield were given a parent respondent questionnaire in 1991 and 1999 based on questions from the International Survey of Asthma and Allergy in Children (ISAAC). Data were obtained regarding the prevalence of asthma and wheeze and current (12 month) prevalences of wheeze attacks, speech limiting wheeze, nocturnal cough and wheeze, and exertional symptoms. RESULTS: The response rates in 1991 and 1999 were 4580/5321 (85.3%) and 5011/6021 (83.2%), respectively. There were significant increases between the two surveys in the prevalence of asthma ever (19.9% v 29.7%, mean difference 11.9%, 95% confidence interval (CI) 10.16 to 13.57, p<0.001), current asthma (10.3% v 13.0%, mean difference 2.7%, 95% CI 1.44 to 4.03, p<0.001), wheeze ever (30.3% v 35.8%, mean difference 5.7%, 95% CI 3.76 to 7.56, p<0.001), wheeze in the previous 12 months (17.0% v 19.4%, mean difference 2.5, 95% CI 0.95 to 4.07, p<0.01), and reporting of medication use (16.9% v 20%, mean difference 3.0%, 95% CI 1.46 to 4.62, p<0.001). There were also significant increases in reported hayfever and eczema diagnoses. CONCLUSIONS: Diagnostic labelling of asthma and lifetime prevalence of wheeze has increased. The current 12 month point prevalence of wheeze has increased but this is confined to occasional symptoms. The increased medication rate may be responsible for the static prevalence of severe asthma symptoms. The significant proportion of children receiving medication but reporting no asthma symptoms identified from our 1999 survey suggests that some children are being inappropriately treated or overtreated.