Complications after intramedullary nail fixation of pathological versus non-pathological femoral shaft fractures: a retrospective cohort study in 233 patients

Background Postoperative adverse events after intramedullary nailing have been reported in patients with metastatic pathological and non-pathological femoral fractures. Other consequences to be considered are readmission and reoperation. Few studies have compared the risks of postoperative adverse events, reoperation, and readmission after intramedullary nailing of pathological and non-pathological femur fractures. This study was designed to test the hypothesis that patients with pathological femoral fractures had more adverse events, readmission, and reoperation following surgical fixation than non-pathological femoral fractures. Methods This was a retrospective observational cohort study, conducted at an academic medical center in Thailand. The data from patients with femoral shaft fractures undergoing long intramedullary nailing, from June 1, 2006, to June 30, 2020, were included. Patients who had a pathological fracture from a primary bone tumor, metabolic bone disease, or inadequate/missing information were excluded. Patients with pathological fractures from metastatic bone disease were assigned to be the pathological group whereas those with traumatic fractures were assigned to be the non-pathological group. The primary outcome was the risk of inpatient adverse events as compared between the two groups. The secondary outcome was the risk of consequences after discharge as compared between the two groups. Outcomes were analyzed by using multivariate logistic regression analysis. Results The total number of patients was 48 in the pathological fracture group and 185 in the non-pathological group. There were significantly higher rates of surgical and medical adverse events in patients with pathological fractures compared to patients with non-pathological fractures. After adjusting for potential confounding factors in multivariate regression analysis, patients with pathological fractures had higher odds of both adverse surgical (adjusted OR 2.43, 95 % CI 1.15–5.13) and medical adverse events (adjusted OR 2.81, 95 % CI 1.13–7.03). Conclusions Patients with metastatic pathological femoral shaft fractures undergoing intramedullary nailing were more likely to experience postoperative adverse events than patients with non-pathological fractures.

A Propensity-Matched Analysis of Survival of Clinically Diagnosed Early-Stage Lung Cancer and Biopsy-Proven Early-Stage Non-Small Cell Lung Cancer Following Stereotactic Ablative Radiotherapy

PurposeStereotactic body radiotherapy (SBRT) has been increasingly regarded as a reasonable option for early-stage lung cancer patients without pretreatment pathologic results, but the efficacy and safety in a Chinese population remains unclear. The aim of this study was to compare survival outcomes and toxicities between patients with clinically diagnosed early-stage lung cancer or biopsy-proven early-stage non-small cell lung cancer and to demonstrate the rationality of this treatment.Material and MethodsFrom May 2012 to December 2018, 56 patients with clinically diagnosed early-stage lung cancer and 60 patients with early-stage biopsy-proven were selected into non-pathological group and pathological group, respectively. Propensity score matching (PSM) was performed to reduce patient selection bias. Survival analysis with log-rank test was used to assess the differences of treatment outcomes, which included local control (LC), progression-free survival (PFS), and overall survival (OS).ResultsThe median age was 76 (range 47–93) years, and the median follow-up time was 58.3 (range 4.3–95.1) months in the cohort without pathologic results. The median age was 74 (range 57–88) years, and the median follow-up time was 56.3 (range 2.6–94) months in the cohort with pathologic results. 45 matched-pair were analyzed. The 5-year LC, PFS, and OS rates in matched-pair patients with or without pathologic biopsy were 85.5% and 89.8%, 40.6% and 70.9%, and 63.2% and 76.1%, respectively. On Kaplan-Meier survival analysis after PSM analysis, there was no significant difference between patients with pathologic results versus patients with no pathologic results in terms of LC (P= 0.498) and OS (P=0.141). Of the matched-pair patients treated with SBRT, only 1 patient experienced grade 3 or above radiation pneumonitis.ConclusionFor early-stage lung cancer patients with medically inoperable or not suitable for invasive diagnosis, SBRT may be a good local treatment.

Optimised method for normal range estimation of standardized uptake values (SUVmax, SUVmean) in liver SPECT/CT images with somatostatin analogue 99mTc-HYNIC-TOC (Tektrotyd).

Background99mTc-HYNIC-TOC (Tektrotyd) is a radiopharmaceutical used for the diagnosis of lesions with overexpression of somatostatin receptors. The purpose of this study was to optimise the method and estimate normal ranges for standardized uptake values of Tektrotyd in healthy livers. MethodsAn analysis of SUVs normal ranges was performed for images acquired in a selected “healthy group” of 42 patients evaluated for NET tumours. The “pathological group” comprised 20 patients with liver lesions detected by scintigraphic imaging. Normal ranges for radiopharmaceutical uptake values were estimated based on the quantitative analysis of images acquired with a GE Healthcare NM/CT 850 gamma camera.ResultsThe method for healthy liver segmentation in SPECT/CT was optimized. The normal range of SUVs for the liver was: SUVbw max [5.2-14.0] g/ml and SUVlbm max [3.5-9.5] g/ml. The relative standard error (relative SE) of activity concentration estimated in the phantom study for the largest hot spheres was: ϕ=37mm- 5.9%, ϕ=28mm- 7.1%, ϕ=22mm- 11.4%, and ϕ=17mm- 22%.Conclusions· Segmentation in the mid-coronal CT image, at one-fourth of the height of the liver measured from the top, with a medium-sized VOI outlined on a given transverse SPECT slice was regarded as the optimal method for estimating normal ranges for standardized uptake values.· It is necessary to standardise quantification methods in the SPECT/CT studies. Our work is a step forward in obtaining standardisation of SPECT/CT SUV calculation methods.· Calculations for radiopharmaceutical uptake in tumours with volumes smaller than 5 ml are biased with a significant measurement error.

Defining candidate mRNA and protein EV biomarkers to discriminate ccRCC and pRCC from non-malignant renal cells in vitro

Renal cell carcinoma (RCC) accounts for over 400,000 new cases and 175,000 deaths annually. Diagnostic RCC biomarkers may prevent overtreatment in patients with early disease. Extracellular vesicles (EVs) are a promising source of RCC biomarkers because EVs carry proteins and messenger RNA (mRNA) among other biomolecules. We aimed to identify biomarkers and assess biological functions of EV cargo from clear cell RCC (ccRCC), papillary RCC (pRCC), and benign kidney cell lines. EVs were enriched from conditioned cell media by size exclusion chromatography. The EV proteome was assessed using Tandem Mass Tag mass spectrometry (TMT-MS) and NanoString nCounter technology was used to profile 770 cancer-related mRNA present in EVs. The heterogeneity of protein and mRNA abundance and identification highlighted the heterogeneity of EV cargo, even between cell lines of a similar pathological group (e.g., ccRCC or pRCC). Overall, 1726 proteins were quantified across all EV samples, including 181 proteins that were detected in all samples. In the targeted profiling of mRNA by NanoString, 461 mRNAs were detected in EVs from at least one cell line, including 159 that were present in EVs from all cell lines. In addition to a shared EV cargo signature, pRCC, ccRCC, and/or benign renal cell lines also showed unique signatures. Using this multi-omics approach, we identified 34 protein candidate pRCC EV biomarkers and 20 protein and 8 mRNA candidate ccRCC EV biomarkers for clinical validation.

Functional Connectivity Derived From Electroencephalogram in Pharmacoresistant Epileptic Encephalopathy Using Cannabidiol as Adjunctive Antiepileptic Therapy

To explore brain function using functional connectivity and network topology derived from electroencephalogram (EEG) in patients with pharmacoresistant epileptic encephalopathy with cannabidiol as adjunctive antiepileptic treatment. Sixteen epileptic patients participated in the study, six of whom had epileptic encephalopathy with a stable dose of cannabidiol Epidiolex (CBD) as adjunctive therapy. Functional connectivity derived from EEG was analyzed based on the synchronization likelihood (SL). The analysis also included reconstructing graph-theoretic measures from the synchronization matrix. Comparison of functional connectivity data between each pathological group with the control group was carried out using a nonparametric permutation test applied to SL values between pairs of electrodes for each frequency band. To compare the association patterns between graph-theoretical properties of each pathological group with the control group, Z Crawford was calculated as a measure of distance. There were differences between pairs of electrodes in all frequency bands evaluated in encephalopathy epileptic patients with CBD adjunctive therapy compared with the control (p < 0.05, permutation test). In the epileptic encephalopathy group without CBD therapy, the SL values were higher than in the control group for the beta, theta, and delta EEG frequency bands, and lower for the alpha frequency band. Interestingly, patients who had CBD as adjunctive therapy demonstrated greater synchronization for all frequency bands, showing less spatial distribution for alpha frequency compared with the control. When comparing both epileptic groups, those patients who had adjunctive CBD treatment also showed increased synchronization for all frequency bands. In epileptic encephalopathy with adjunctive CBD therapy, the pattern of differences for graph-theoretical measures according to Z Crawford indicated less segregation and greater integration suggesting a trend towards the random organization of the network principally for alpha and beta EEG bands. This exploratory study revealed a tendency to an overconnectivity with a random network topology mainly for fast EEG bands in epileptic encephalopathy patients using CBD adjunctive therapy. It can therefore be assumed that the CBD treatment could be related to inhibition of the transition of the interictal to ictal state and/or to the improvement of EEG organization and brain function.

EMG ACTIVITY OF UPPER LIMB MUSCLES IN THE CASE OF NERVOUS MUSCULAR TRANSMISSION’S PATHOLOGY IN THE HUMAN

In many cases of a disease or an injury of the upper extremity nerve impulses are impaired. The high level of diagnostic and tactical errors in upper limb's nerve damage often leads to poor treatment outcomes. An important, and sometimes decisive, factor in the choice of treatment is the assessment of the functional state of the nerves and muscles of the affected limb segment. The purpose of this testing is to study the features of the upper limb muscles's EMG activity in normal and in the case of clinical pathology of neuromuscular transmission. 24 volunteers between the ages of 17 and 32, both male and female, with the right profile of manual asymmetry took part in the study. While dividing into groups, the presence of the diagnosted pathology of the upper right limb's neuromuscular transmission was taken into account. Accordingly, we created a "pathological" (n = 8) and "healthy" (n = 16) groups. In both groups, we sequentially recorded the M-response of the abductor pollicis brevis during stimulation of the nerve medianus as well as the M-response of the abductor digiti minimi during stimulation of the nerve ulnaris. The M-response amplitude, residual latency (RL), and excitation propagation rate (EPR) were analyzed. It has been established that the amplitudes of the M-responce during EMG stimulation of the abductor pollicis brevis and the abductor digiti minimi were lower in pathological group than tin normal. According to our results, RL of examined muscles' M-response increased with distanting away from the stimulation point (muscle's working point). In the case of pathology we observed longer RL of M-responce than in healthy testees. In the case of stimulation of the abductor pollicis brevis EPR was comparely higher on the elbow-shoulder segment and the wrist-shoulder segment in the pathological group, wereas while stimulation of the abductor digiti minimi we established inverse relationship. EPR in all segments, namely the wrist-shoulder and elbow-shoulder, was lower in the pathologic group compared to the norm.

Correlation of admission labour admission test in low risk pregnancies with pregnancy outcome

Background: Aim of the study was to evaluate the role of NST (labour admission test) as a screening method in management of low risk pregnancies and to study the correlation of NST with fetal outcome.Methods: A prospective observational study conducted over 500 patients managed at our centre after proper evaluation. Patients were evaluated for mode of delivery and neonatal outcome.Results: The maximum number 352 of patients belonged to 20-30 years age group, 113 patients belonged to 31-35 age group. 200 patients were of 37-40 weeks gestation and 185 were of 40-41 weeks gestation. There were 125 patients in the 41-42 weeks gestational period. Among the 500 pregnant mothers who were included in the study 82.6% had Normal NST, 11.6% had suspicious and 5.8% had pathological NST. Cesarean rate was 14.4% in normal NST group, 58.62% in suspicious group and 72.41% in pathological group study. 6.77% in Normal group had meconium stained liquor at delivery whereas 29.31% in suspicious group and 37.93% in pathological group had same.Conclusions: The non-stress test is an important screening tool to identity the fetus in jeopardy in utero. This enables an appropriate timely intervention to achieve the most favorable outcome.

Prevalence of infections with Clostridium difficile on potential pathology groups

Enterotoxins produced by Clostridium difficile cause a series of biochemical and immunological manifestations in the cascade leading to alteration of the enterocitus cytoskeleton, intestinal inflammation and diarrhea that can greatly impair the patient’s biological status. The genome of the Clostridium difficile bacterium shows a series of evolutionary adaptations that can give it a high degree of resistance or adaptability to many known pharmacological classes. Changing the diversity of intestinal microbiota induced by the use of antibiotics creates a favorable environment from all points of view for Clostridium difficile spore activity. The theme addresses in an original way but related to the epidemiological studies presented in the literature a correlative aspect between the pathological group and the infection with Clostridium difficile. From the data presented, there is a direct correlation between Clostridium difficile infection and the use of antibiotic therapy as a curative or preventive treatment. Gastrointestinal and neurological pathologies, due to the use of curative but also preventive antibiotic therapy, are at increased risk for the installation of Clostridium difficile infection. The study presented may be a first step in raising awareness of the rational use of antibiotics and avoiding non-assisted community antibiotic therapy.

Preprint: Altered decision-making under uncertainty in unmedicated mood and anxiety disorders

In daily life we are constantly faced with decisions that have uncertain outcomes. This uncertainty can lead to feelings of anxiety. However, the reciprocal role that anxiety plays in altering the decisions made under uncertainty is not fully understood. This is important, because psychological treatments for anxiety disorders attempt to alter anxiety-related decision-making. In this study we therefore probed the computational basis of decision-making under uncertainty in individuals with high levels of mood and anxiety symptoms. Specifically, healthy individuals (N=88) and individuals with mood and anxiety disorders (N=44) were asked to choose between four competing slot machines (‘four armed bandit’) with fluctuating, uncertain, outcomes (i.e. rewards and/or punishments, or neither). Decisions were made during periods of safety and environmental stress (threat of unpredictable shock). We predicted that anxious individuals under stress would learn faster about punishments, and exhibit choices that were more affected by them. We formalized these hypotheses in terms of parameter values – punishment learning rate and punishment sensitivity respectively - in reinforcement learning accounts of behaviour. We found no evidence for an effect on punishment choice sensitivity in the pathological group, even under elevated stress. However individuals with high anxiety symptoms did have higher learning rates for punishment across all conditions. The behaviour of the pathological group was also apparently more random, with a greater influence of a lapse parameter in the model across conditions. Overall, these data suggest that anxious individuals do not weigh negative outcomes more heavily; rather they are quicker to update their behaviour in response to negative (but not positive) outcomes. This suggests that, when treating anxiety, we should not seek to blunt responses to negative outcomes, but instead encourage anxious individuals to integrate information over longer horizons when bad things happen. As such, these findings provide a formal mathematical framework for developing psychological treatment strategies for mood and anxiety disorders.

Expression of HIF-1α in keloids and its correlation with inflammatory responses and apoptosis

The aim of this study was to investigate the expression of hypoxia-inducible factor-1α (HIF-1α) in keloids and its correlation with inflammatory responses and apoptosis. The keloid specimens resected in our hospital from November 2015 to February 2017 were selected as the pathological group, and the normal skin tissues from our hospital during the same period were selected as the control group. The expression of HIF-1α, inflammatory response cytokines, and apoptotic molecules in the tissues of two groups were detected. The messenger RNA (mRNA) expression of HIF-1α in the keloids in the pathological group was significantly higher than that in the control group, and the mRNA expression of interleukin (IL)-1β, IL-2, IL-6, and tumor necrosis factor (TNF)-α in the pathological group was significantly higher than those in the control group. The mRNA expression of Bax in the pathological group was significantly higher than that in the control group. The mRNA expression of Bcl-2, livin, and hPEBP4 in the pathological group was significantly lower than that in the control group. Pearson test showed that there was a positive correlation between the mRNA expression of HIF-1α and inflammatory cytokines including IL-1β, IL-2, IL-6, and TNF-α. There were also a positive correlation between the mRNA expression of HIF-1α and Bax and a negative correlation between the mRNA expression of HIF-1α and Bcl-2, livin, and hPEBP4. In conclusion, HIF-1α was highly expressed in keloids and closely related to inflammatory response cytokines and apoptosis molecules. Increased expression of HIF-1α in keloids may be an important factor in inflammatory responses and increased apoptosis in skin tissues.