J. Clin. Med., Volume 8, Issue 11 (November 2019) – 267 articles

Escherichia coli and salivary Klebsiella oxytoca and Staphylococcus saccharolyticus were subjected to different concentrations of silver nanoparticles (AgNPs), namely: 12.5, 50, and 100 µg mL⁻¹. Matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry (MALDI-TOF MS) spectra were acquired after specified periods: 0, 1, 4, and 12 h. For study of volatile metabolites, headspace solid-phase microextraction coupled to gas chromatography/mass spectrometry (HS-SPME-GC-MS) was employed—AgNPs were added to bacteria cultures and the headspace was analyzed immediately and after 12 h of incubation. Principal components analysis provided discrimination between clusters of protein profiles belonging to different strains. Canonical correlation, network analysis, and multiple linear regression approach revealed that dimethyl disulfide, dimethyl trisulfide, 2-heptanone, and dodecanal (related to the metabolism of sulfur-containing amino acids and fatty acids synthesis) are exemplary molecular indicators, whose response variation deeply correlated to the interaction with bacteria. Therefore, such species can serve as biomarkers of the agent’s effectiveness. The present investigation pointed out that the used approaches can be useful in the monitoring of response to therapeutic treatment based on AgNPs. Furthermore, biochemical mechanisms enrolled in the bactericidal action of nanoparticles can be applied in the development of new agents with enhanced properties. Full article

Life expectancy is on the rise and, concurrently, the demand for total knee arthroplasty (TKA), which lasts a lifetime, is increasing. To meet this demand, improved TKA designs have been introduced. Recent advances in radiography and manufacturing techniques have enabled the production of patient-specific TKA. Nevertheless, concerns regarding the wear performance, which limit the lifespan of TKA, remain to be addressed. This study aims at reducing the wear in patient-specific TKA using design optimization and parametric three-dimensional (3D) finite-element (FE) modelling. The femoral component design was implemented in a patient-specific manner, whereas the tibial insert conformity remained to be determined by design variables. The gait cycle loading condition was applied, and the optimized model was validated by the results obtained from the experimental wear tests. The wear predictions were iterated for five million gait cycles using the computational model with force-controlled input. Similar patterns for internal/external rotation and anterior/posterior translation were observed in both initial and optimal models. The wear rates for initial and optimal models were recorded as 23.2 mm³/million cycles and 16.7 mm³/million cycles, respectively. Moreover, the experimental wear rate in the optimal design was 17.8 mm³/million cycles, which validated our optimization procedure. This study suggests that tibial insert conformity is an important factor in influencing the wear performance of patient-specific TKA, and it is capable of providing improved clinical results through enhanced design selections. This finding can boost the future development of patient-specific TKA, and it can be extended to other joint-replacement designs. However, further research is required to explore the potential clinical benefits of the improved wear performance demonstrated in this study. Full article

Optic neuritis (ON) is a common manifestation of multiple sclerosis (MS). Aiming to evaluate the retinal nerve fiber layer (RNFL) with optical coherence tomography (OCT), patients with relapsing-remitting (RR) MS experiencing ON were consecutively enrolled. RNFL, ganglion cell layer (GCL), foveal thickness, and macular volume were evaluated in both the ON and unaffected (nON) eye within six days from the relapse onset (T0) and after six months (T1). Ninety patients were enrolled. At T0, ON eyes showed a significantly increased RNFL when compared to the nON eyes (129.1 ± 19.5 vs. 100.5 ± 10.1, p < 0.001). At T1 versus T0, the ON eyes showed a thinner RNFL (129.1 ± 19.5 vs. 91.6 ± 20.2, p < 0.001) and a significantly decreased GCL (80.4 ± 8.8 vs. 73.8 ± 11.6; p < 0.005). No differences were found in the nON group in retinal parameters between T0 and T1. A multivariate logistic regression analysis showed that a higher number of relapses (not ON) and a greater swelling of RNFL at T0 were associated with poor recovery. The assessment of RNFL through OCT during and after ON could be used to predict persistent visual disability. Full article

Background: Attention in the 2000s on the importance of mammographic density led us to study screening sensitivity, breast cancer incidence, and associations with risk factors by mammographic density in Danish breast cancer screening programs. Here, we summarise our approaches and findings. Methods: Dichotomized density codes: fatty, equal to BI-RADS density code 1 and part of 2, and other mixed/dense data from the 1990s—were available from two counties, and BI-RADS density codes from one region were available from 2012/13. Density data were linked with data on vital status, incident breast cancer, and potential risk factors. We calculated screening sensitivity by combining data on screen-detected and interval cancers. We used cohorts to study high density as a predictor of breast cancer risk; cross-sectional data to study the association between life style factors and density, adjusting for age and body mass index (BMI); and time trends to study the prevalence of high density across birth cohorts. Results: Sensitivity decreased with increasing density from 78% in women with BI-RADS 1 to 47% in those with BI-RADS 4. For women with mixed/dense compared with those with fatty breasts, the rate ratio of incident breast cancer was 2.45 (95% CI 2.14–2.81). The percentage of women with mixed/dense breasts decreased with age, but at a higher rate the later the women were born. Among users of postmenopausal hormone therapy, the percentage of women with mixed/dense breasts was higher than in non-users, but the patterns across birth cohorts were similar. The occurrence of mixed/dense breast at screening age decreased by a z-score unit of BMI at age 13—odds ratio (OR) 0.56 (95% CI 0.53–0.58)—and so did breast cancer risk and hazard ratio (HR) 0.92 (95% CI 0.84–1.00), but it changed to HR 1.01 (95% CI 0.93–1.11) when controlled for density. Age and BMI adjusted associations between life style factors and density were largely close to unity; physical activity OR 1.06 (95% CI 0.93–1.21); alcohol consumption OR 1.01 (95% CI 0.81–1.27); air pollution OR 0.96 (95% 0.93–1.01) per 20 μg/m³; and traffic noise OR 0.94 (95% CI 0.86–1.03) per 10 dB. Weak negative associations were seen for diabetes OR 0.61 (95% CI 0.40–0.92) and cigarette smoking OR 0.86 (95% CI 0.75–0.99), and a positive association was found with hormone therapy OR 1.24 (95% 1.14–1.35). Conclusion: Our data indicate that breast tissue in middle-aged women is highly dependent on childhood body constitution while adult life-style plays a modest role, underlying the need for a long-term perspective in primary prevention of breast cancer. Full article

PNPT1 (PNPase—polynucleotide phosphorylase) is involved in multiple RNA processing functions in the mitochondria. Bi-allelic pathogenic PNPT1 variants cause heterogeneous clinical phenotypes affecting multiple organs without any established genotype–phenotype correlations. Defects in PNPase can cause variable combined respiratory chain complex defects. Recently, it has been suggested that PNPase can lead to activation of an innate immune response. To better understand the clinical and molecular spectrum of patients with bi-allelic PNPT1 variants, we captured detailed clinical and molecular phenotypes of all 17 patients reported in the literature, plus seven new patients, including a 78-year-old male with the longest reported survival. A functional follow-up of genomic sequencing by cDNA studies confirmed a splicing defect in a novel, apparently synonymous, variant. Patient fibroblasts showed an accumulation of mitochondrial unprocessed PNPT1 transcripts, while blood showed an increased interferon response. Our findings suggest that functional analyses of the RNA processing function of PNPase are more sensitive than testing downstream defects in oxidative phosphorylation (OXPHPOS) enzyme activities. This research extends our knowledge of the clinical and functional consequences of bi-allelic pathogenic PNPT1 variants that may guide management and further efforts into understanding the pathophysiological mechanisms for therapeutic development. Full article

Chronic rhinitis (CR) is divided into two main categories: allergic rhinitis (AR) and nonallergic rhinitis (NAR). These conditions are more recognizable to an experienced clinician, as they can be more clearly demarcated diagnostically. However, an additional 30% to 50% of patients with CR might have an overlap of NAR and AR, referred to as mixed rhinitis (MR). Progress in elucidating the pathophysiologic mechanisms behind MR and NAR has been made in the past several years, and there are now several guidelines published to assist the clinician in accurately diagnosing AR, NAR, and MR. Clinical history and subjective symptoms can provide clues for differentiating AR from MR and NAR, but allergy testing is recommended to confirm these conditions. Progress in accurately diagnosing patients with CR will be made as studies incorporate subjective (i.e., validated questionnaires such as the irritant index questionnaire (IIQ), medication responsiveness, and quality-of-life tools) and objective (i.e., nasal cytologic testing, nasal provocation, and biomarkers) methods characterizing rhinitis subtypes. Full article

Background: Choriocarcinoma is a rare malignant disease that is usually associated with a gestational event. Lung metastasis with no evident primary origin and choriocarcinoma, which mimics features of non-small-cell lung cancer, might be misdiagnosed as adenocarcinoma or large-cell carcinoma. This is a pivotal clinical concern since the tumor can lead to various symptoms, seriously affecting the quality of life and can escalate rapidly, with a high mortality rate, compared to lung cancer. Methods: We reported a case of a 37-year-old woman with a history of one-year enhancement of beta-human chorionic gonadotropin levels and only a single nodule in the right upper lobe, with no abnormal findings on the gynecological investigation. Then we retrospectively examined all cases treated in the Division of Thoracic Surgery at the European Institute of Oncology in the last twenty years (from 1998 to 2018). Results: This was the first time in our experience that choriocarcinoma presentation was with a single nodule without a gynecological finding. Moreover, the differential diagnosis between lung carcinoma and choriocarcinoma was achieved only after surgical removal. Conclusions: As confirmed by our literature search, precise and expedited differential diagnosis is essential in choriocarcinoma care (both with single or multiple metastases), to successfully remove the tumor and increase the patient’s chances of survival. Full article

Artificial nutrition, including enteral (EN) and parenteral (PN) nutrition, is indicated whenever adequate oral nutrition fails to sufficiently supply the necessary nutrients to the body. It is a convenient, efficacious, safe, and well-tolerated form of clinical nutrition in the hospital and home setting. EN is administered via nasogastric tube or ostomies while PN usually requires a central venous access for administration, straight into the blood stream. The infused nutrients can then be taken up directly by the different organs. PN is targeted as a single daily portion formulated as an oil-in-water emulsion providing the necessary substrates for the catabolic and anabolic metabolism including macro- and micronutrients and fluids. PN has a complex pharmaceutical composition—all-in-one admixture—and its compounding or ready-to-use preparation. The use of PN is more challenging and more expensive compare to the use of EN, commercially available as ready-to-use formulations. EN and concomitant medication is highly challenging. Upon incorrect handling and administration, PN is associated with potentially severe or even fatal complications, mostly relating to the central venous access (e.g., catheter-related sepsis) or to a metabolic intolerance (e.g., hyperglycemia, refeeding syndrome) because of inappropriate administration. A correct order of admixing, correct dosing, and administration of the artificial is crucial for safety and efficacy; clinical and biochemical monitoring of the patient and treatment regimen adaption are necessary. The high number of reactive solutes allow only limited stability of a ready-to-use PN admixture. The potential for numerous incompatibilities and interactions renders PN admixtures generally unsuitable as drug vehicle. Laboratory compatibility and stability testing and pharmaceutical expertise are a prerequisite to define the PN composition including nutrients or even drugs admixed to define the appropriate and individualized nutrition and medication regimen. The aim of this narrative review is to present the actual state-of-the-art to deliver best quality artificial nutrition with special regard on pharmaceutical aspects such as instabilities, incompatibilities, and concomitant co-medication. Full article

Percutaneous cardiovascular interventions have changed dramatically in recent years, and the impetus given by the rapid implementation of novel techniques and devices have been mirrored by a refinement of antithrombotic strategies for secondary prevention, which have been supported by a significant burden of evidence from clinical studies. In the current manuscript, we aim to provide a comprehensive, yet pragmatic, revision of the current available evidence regarding antithrombotic strategies in the domain of percutaneous cardiovascular interventions. We revise the evidence regarding antithrombotic therapy for secondary prevention in coronary artery disease and stent implantation, the complex interrelation between antiplatelet and anticoagulant therapy in patients undergoing percutaneous coronary intervention with concomitant atrial fibrillation, and finally focus on the novel developments in the secondary prevention after structural heart disease intervention. A special focus on treatment individualization is included to emphasize risk and benefits of each therapeutic strategy. Full article

Background: Maternal stress during pregnancy can affect fetal development during certain sensitive periods. Objective: To longitudinally assess maternal hair cortisol levels during pregnancy, and the postpartum along with neonatal hair cortisol levels that could be associated with infant neurodevelopment at six months of age. Methods: A sample of 41 pregnant women longitudinally assessed during the first, second, and third trimester and the postpartum, along with their 41 full-term neonates participated in this study. Hair cortisol levels were assessed from participants. Infant neurodevelopment was assessed by means of the Bayley Scale of Infants Development, Third Edition at age six months. Results: Maternal hair cortisol levels in the first and second trimester accounted for 24% and 23%, respectively, of variance of infant gross motor development (p < 0.05). Maternal hair cortisol levels during the postpartum accounted for 31% of variance of infant cognitive development (p < 0.05), and 25% of variance of infant gross motor development (p < 0.05). Neonatal hair cortisol levels accounted for 28% of variance of infant gross motor development (p < 0.05). Conclusions: The preconception and prenatal time are sensitive periods related to infant neurodevelopment along with the cortisol levels surrounding the fetus while in the womb. Pregnant women could be assessed for hair cortisol levels while attending a prenatal appointment. Full article

Systemic lidocaine can provide satisfactory post-operative analgesia in adults. In this study, we assessed whether intravenous lidocaine is effective for post-operative analgesia and recovery in children undergoing laparoscopic inguinal hernia repair. A total of 66 children aged from six months to less than six years were classified in either the lidocaine (L) or control (C) groups. Children in Group L received a lidocaine infusion (a bolus dose of 1 mL kg⁻¹, followed by a 1.5 mg kg⁻¹ h⁻¹ infusion), whereas Group C received the same volume of 0.9% saline. The primary outcome was the number of patients who presented face, legs, activity, crying and consolability (FLACC) scores of four or more, and therefore received rescue analgesia in the post-anesthesia recovery care unit (PACU). Secondary outcomes included the highest FLACC score in the PACU, FLACC, and the parents’ postoperative pain measure (PPPM) score at 48 h post-operation, as well as side effects. The number of children who received rescue analgesia in the PACU was 15 (50%) in Group L and 22 (73%) in Group C (p = 0.063). However, the highest FLACC score in PACU was lower in Group L (3.8 ± 2.4) than in Group C (5.3 ± 2.7) (p = 0.029). In conclusion, systemic lidocaine did not reduce the number of children who received rescue analgesia in PACU. Full article

Antisynthetase syndrome (ASSD) is a rare clinical condition that is characterized by the occurrence of a classic clinical triad, encompassing myositis, arthritis, and interstitial lung disease (ILD), along with specific autoantibodies that are addressed to different aminoacyl tRNA synthetases (ARS). Until now, it has been unknown whether the presence of a different ARS might affect the clinical presentation, evolution, and outcome of ASSD. In this study, we retrospectively recorded the time of onset, characteristics, clustering of triad findings, and survival of 828 ASSD patients (593 anti-Jo1, 95 anti-PL7, 84 anti-PL12, 38 anti-EJ, and 18 anti-OJ), referring to AENEAS (American and European NEtwork of Antisynthetase Syndrome) collaborative group’s cohort. Comparisons were performed first between all ARS cases and then, in the case of significance, while using anti-Jo1 positive patients as the reference group. The characteristics of triad findings were similar and the onset mainly began with a single triad finding in all groups despite some differences in overall prevalence. The “ex-novo” occurrence of triad findings was only reduced in the anti-PL12-positive cohort, however, it occurred in a clinically relevant percentage of patients (30%). Moreover, survival was not influenced by the underlying anti-aminoacyl tRNA synthetase antibodies’ positivity, which confirmed that antisynthetase syndrome is a heterogeneous condition and that antibody specificity only partially influences the clinical presentation and evolution of this condition. Full article

The effects of non-invasive ventilation (NIV) in addition to supplemental oxygen on exercise performance in patients with chronic obstructive pulmonary disease (COPD) with hyperinflation and exercise-induced desaturation (EID) remain unclear. We hypothesized that these patients would benefit from NIV and that this effect would be an add-on to oxygen therapy. Thirteen COPD patients with a residual volume >150% of predicted, normal resting arterial oxygen pressure (P_aO₂) and carbon-dioxide pressure (P_aCO₂) and EID during a six-minute walk test were included. Patients performed four constant work-rate treadmill tests, each consisting of two exercise bouts with a recovery period in between, wearing an oronasal mask connected to a ventilator and oxygen supply. The ventilator was set to the following settings in fixed order with clockwise rotation: Sham (continuous positive airway pressure (CPAP) 2 cm H₂O, FiO₂ 21%), oxygen (CPAP 2 cm H₂O, FiO₂ 35%), NIV and oxygen (inspiratory positive airway pressure (IPAP) 14 cm H₂O/expiratory positive airway pressure (EPAP) 6 cm H₂O, inspired oxygen fraction (FiO₂) 35%), intermittent (walking: Sham setting, recovery: NIV and oxygen setting). During the first exercise, bout patients walked further with the oxygen setting compared to the sham setting (225 ± 107 vs 120 ± 50 meters, p < 0.05), but even further with the oxygen/NIV setting (283 ± 128 meters; p < 0.05). Recovery time between two exercise bouts was shortest with NIV and oxygen. COPD patients with severe static hyperinflation and EID benefit significantly from NIV in addition to oxygen during exercise and recovery. Full article

Ischemic stroke (IS) is multifactorial causation combining with traditional cardiovascular disease (CVD) and genetic risk factors. Combined effects of MMP-7, MMP-8 and MMP-26 on the risk of IS remain incompletely understood. We aimed to assess individual and joint effects for IS risk by weighted genetic risk score (wGRS) from these three genes and traditional CVD risk factors. A case-control study including 500 cases with IS and 500 stroke-free healthy controls frequency-matched with cases by age and sex was conducted. The wGRS was a weighted average of the number of risk genotype across selected SNPs from MMP-7, MMP-8 and MMP-26. Multivariate logistic regression models were used to analyze the relationship between wGRS and risk of IS. A wGRS in the second tertile was associated with a 1.5-fold increased risk of IS compared with the lowest tertile after adjusting for traditional CVD risk factors. Compared to subjects with low genetic and low modifiable CVD risk, those with high genetic and high modifiable CVD risk had the highest risk of IS (adjusted-OR = 5.75). In conclusion, higher wGRS was significantly associated with an increased risk for IS. A significant interaction between genetic and traditional CVD risk factors was also found on the risk of IS. Full article

Background: Sleep duration is an identified risk factor for adverse health outcomes. As the endocrine system is closely intertwined with sleep duration and quality, the association between endocrine dysfunction and sleep has been evaluated. Thyroid function, particularly that related to thyrotropin (TSH), is also known to be influenced by the sleep/awake status and circadian rhythm. Additionally, a link between sleep duration and autoimmunity, which is a common cause of thyroid dysfunction, has been suggested; however, depending on the sleep deprivation method used in studies, the effects of sleep on thyroid function vary. The relationship between subclinical thyroid dysfunction and sleep duration is poorly documented. Thus, to elucidate the impact of sleep on thyroid function, we investigated the association of subclinical thyroid dysfunction with sleep duration using representative data from the sixth Korea National Health and Nutrition Examination Survey, conducted from 2013 to 2015. Methods: In all, 4945 participants (2543 male and 2402 female) were included after excluding subjects using the following criteria: <19 years of age, free T4 level outside the normal range, history of thyroid disease, or incomplete data. The population was classified into three groups: short sleeper (<7 h/day), normal sleeper (7–8 h/day), and long sleeper (>8 h/day). The odds ratio (OR) for subclinical hypothyroidism or hyperthyroidism according to sleep duration was evaluated. Results: The short, normal, and long sleeper groups consisted of 2097, 2514, and 334 subjects, respectively. On multiple logistic regression analysis, compared to normal sleepers, short sleepers showed a significantly increased risk of subclinical hyperthyroidism (OR 1.37, 95% confidential interval (CI) 1.02–1.84, p = 0.036), while the risk of subclinical hypothyroidism in short sleepers was not elevated. Comparing long sleepers to normal sleepers, the OR for subclinical hyperthyroidism and hypothyroidism was 1.79 (95% CI 1.12–2.86, p = 0.015) and 1.91 (95% CI 1.03–3.53, p = 0.039), respectively. Conclusions: Both shorter and longer sleep durations were associated with an increase in the risk of subclinical thyroid dysfunction compared to the optimal sleep duration. This analysis of representative population data shows that sleep duration could intertwine with thyroid function resulting in increased risk of subclinical thyroid dysfunction. Full article

Background: DOVE (Determining Effects of Platelet Inhibition on Vaso-Occlusive Events) was a Phase 3, randomized, double-blind, placebo-controlled study conducted in children with sickle cell anemia at 51 sites in 13 countries across four continents. Procedure: Data from DOVE were assessed for regional differences in subject phenotype and treatment. Demographics, baseline clinical and laboratory data, hydroxyurea (HU) use, vaso-occlusive crisis (VOCs; composite endpoint of painful crisis or acute chest syndrome (ACS)), serious adverse events (SAEs), hospitalization, and treatments were compared across the Americas, Europe, North Africa/Middle East, and Sub-Saharan Africa (SSA). Results: Race, body mass index, and blood pressures differed by region. Pre-enrollment VOCs were highest in the Americas. For subjects not on HU, baseline hemoglobin was lowest in SSA; reticulocyte count was lowest in the Americas. Within SSA, Kenya subjects presented higher baseline hemolysis. Painful crisis was the most common SAE, followed by ACS in the Americas and infections in other regions. VOC rate and percentage of VOC hospitalizations were highest in Europe. Regardless of region, most VOCs were treated with analgesics; approximately half were treated with intravenous fluids. The proportion of VOC-related transfusions was greatest in Europe. Lengths of hospital stay were similar across regions. Conclusions: Overall differences in SAEs and hospitalization for VOCs may be due to cultural diversities, resource utilization, disease severity, or a combination of factors. These data are of importance for the planning of future trials in SCA in a multinational setting. Full article

Extremely low-frequency pulsed electromagnetic field (ELF-PEMF) therapy is proposed to support bone healing after injuries and surgical procedures, being of special interest for elderly patients. This study aimed at investigating the effect of a specific ELF-PEMF, recently identified to support osteoblast function in vitro, on bone healing after high tibial osteotomy (HTO). Patients who underwent HTO were randomized to ELF-PEMF or placebo treatment, both applied by optically identical external devices 7 min per day for 30 days following surgery. Osseous consolidation was evaluated by post-surgical X-rays (7 and 14 weeks). Serum markers were quantified by ELISA. Data were compared by a two-sided t-test (α = 0.05). Device readouts showed excellent therapy compliance. Baseline parameters, including age, sex, body mass index, wedge height and blood cell count, were comparable between both groups. X-rays revealed faster osseous consolidation for ELF-PEMF compared to placebo treatment, which was significant in patients ≥50 years (∆_mean = 0.68%/week; p = 0.003). Findings are supported by post-surgically increased bone-specific alkaline phosphatase serum levels following ELF-PEMF, compared to placebo (∆_mean = 2.2 µg/L; p = 0.029) treatment. Adverse device effects were not reported. ELF-PEMF treatment showed a tendency to accelerate osseous consolidation after HTO. This effect was stronger and more significant for patients ≥50 years. This ELF-PEMF treatment might represent a promising adjunct to conventional therapy supporting osseous consolidation in elderly patients. Level of Evidence: I. Full article

Evaluating changes induced by immunotherapies (IT) on conventional magnetic resonance imaging (MRI) is difficult because those treatments may produce inflammatory responses. To explore the potential contribution of advanced MRI to distinguish pseudoprogression (PsP) and true tumor progression (TTP), and to identify patients obtaining therapeutic benefit from IT, we examined aMRI findings in newly diagnosed glioblastoma treated with dendritic cell IT added to standard treatment. We analyzed longitudinal MRIs obtained in 22 patients enrolled in the EUDRACT N° 2008-005035-15 trial. According to RANO criteria, we observed 18 TTP and 8 PsP. Comparing MRI performed at the time of TTP/PsP with the previous exam performed two months before, a difference in cerebral blood volume ΔrCBV_max ≥ 0.47 distinguished TTP from PsP with a sensitivity of 67% and specificity of 75% (p = 0.004). A decrease in minimal apparent diffusion coefficient rADC_min (1.15 vs. 1.01, p = 0.003) was observed after four vaccinations only in patients with a persistent increase of natural killer cells (response effectors during IT) in peripheral blood. Basal rADC_min > 1 was independent predictor of longer progression free (16.1 vs. 9 months, p = 0.0001) and overall survival (32.8 vs. 17.5 months, p = 0.0005). In conclusion, rADC predicted response to immunotherapy and survival; Apparent Diffusion Coefficient (ADC) and Cerebral Blood Volume (CBV) modifications over time help differentiating PsP from TTP at onset. Full article

Although seizures are frequently seen after cerebrovascular accidents, their effects on long-term outcome in stroke patients are still unknown. Therefore, the aim of this study was to investigate the relationship between post-stroke seizures and the risk of long-term disability and mortality in stroke patients. This study is part of a larger population-based study. All patients were prospectively followed up by a face-to-face interview or a structured telephone interview. We enrolled 635 patients with first-ever stroke and without a history of seizures. Prevalence of ischemic stroke (IS) was 85.2%, while the remaining 14.8% of patients were affected by intracerebral hemorrhage (ICH). During the study period, 51 subjects (8%) developed post-stroke seizures. Patients with post-stroke seizures were younger, had a higher prevalence of ICH, had a more severe stroke at admission, were more likely to have an IS involving the total anterior circulation, and were more likely to have a lobar ICH than patients without seizures. Moreover, subjects with seizures had more frequently hemorrhagic transformation after IS and cortical strokes. At 24 months, the risk of disability in patients with seizures was almost twice than in those without seizures. However, the negative effect of seizures disappeared in multivariate analysis. Kaplan-Meier survival curves at 12 years were not significantly different between patients with and without post-stroke seizures. Using the Cox multivariate analysis, age, NIHSS at admission, and pre-stroke mRS were independently associated with all-cause long-term mortality. In our sample, seizures did not impair long-term outcome in patients affected by cerebrovascular accidents. The not significant, slight difference in favor of a better survival for patients with seizures may be attributed to the slight age difference between the two groups. Full article

Anastomotic leakage (AL) following gastroesophageal cancer surgery remains a serious postoperative complication. This systematic review aims to provide an overview of investigated biomarkers for the early detection of AL following esophagectomy, esophagogastrectomy and gastrectomy. All published studies evaluating the diagnostic accuracy of biomarkers predicting AL following gastroesophageal resection for cancer were included. The Embase, Medline, Cochrane Library, PubMed and Web of Science databases were searched. Risk of bias and applicability were assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) 2 tool. Twenty-four studies evaluated biomarkers in the context of AL following gastroesophageal cancer surgery. Biomarkers were derived from the systemic circulation, mediastinal and peritoneal drains, urine and mediastinal microdialysis. The most commonly evaluated serum biomarkers were C-reactive protein and leucocytes. Both proved to be useful markers for excluding AL owing to its high specificity and negative predictive values. Amylase was the most commonly evaluated peritoneal drain biomarker and significantly elevated levels can predict AL in the early postoperative period. The associated area under the receiver operating characteristic (AUROC) curve values ranged from 0.482 to 0.994. Current biomarkers are poor predictors of AL after gastroesophageal cancer surgery owing to insufficient sensitivity and positive predictive value. Further research is needed to identify better diagnostic tools to predict AL. Full article

The high prevalence of antibiotic resistance in Helicobacter pylori has become a great challenge in Iran. The genetic mutations that contribute to the resistance have yet to be precisely identified. This study aimed to investigate the prevalence of antibiotic resistance and virulence markers in Iranian H. pylori isolates and to analyze if there is any association between resistance and genotype. Antibiotic susceptibility patterns of 68 H. pylori isolates were investigated against metronidazole, clarithromycin, amoxicillin, rifampicin, ciprofloxacin, levofloxacin, and tetracycline by the agar dilution method. The frxA, rdxA, gyrA, gyrB, and 23S rRNA genes of the isolates were sequenced. The virulence genotypes were also determined using PCR. Metronidazole resistance was present in 82.4% of the isolates, followed by clarithromycin (33.8%), ciprofloxacin (33.8%), rifampicin (32.4%), amoxicillin (30.9%), levofloxacin (27.9%), and tetracycline (4.4%). Overall, 75% of the isolates were resistant to at least two antibiotics tested and considered as a multidrug resistance (MDR) phenotype. Most of the metronidazole-resistant isolates carried frameshift mutations in both frxA and rdxA genes, and premature termination occurred in positions Q5Stop and Q50Stop, respectively. Amino acid substitutions M191I, G208E, and V199A were predominantly found in gyrA gene of fluoroquinolone-resistant isolates. A2143G and C2195T mutations of 23S rRNA were found in four clarithromycin-resistant isolates. Interestingly, significant associations were found between resistance to metronidazole (MNZ) and cagA-, sabA-, and dupA-positive genotypes, with p = 0.0002, p = 0.0001, and p = 0.0001, respectively. Furthermore, a significant association was found between oipA “on” status and resistance to amoxicillin (AMX) (p = 0.02). The prevalence of H. pylori antibiotic resistance is high in our region, particularly that of metronidazole, clarithromycin, ciprofloxacin, and MDR. Simultaneous screening of virulence and resistance genotypes can help clinicians to choose the appropriate therapeutic regime against H. pylori infection. Full article

Primary hypertension describes abnormally-high systolic/diastolic blood pressure in a resting condition caused by various genetic or environmental risk factors. Remarkably, severe complications, such as ischemic cardiovascular disease, stroke, and chronic renal disease have led to primary hypertension becoming a huge burden for almost one-third of the total population. Medication is the major regimen for treating primary hypertension; however, recent medications may have adverse effects that attenuate energy levels. Hence, the search for new hypotensive agents from folk or traditional medicine may be fruitful in the discovery and development of new drugs. This review assembles recent findings for natural antihypertensive agents, extracts, or decoctions published in PubMed, and provides insights into the search for new hypotensive compounds based on blood-pressure regulating mechanisms, including the renin-angiotensin-aldosterone system and the sympathetic/adrenergic receptor/calcium channel system. Full article

Background: Occult paroxysmal atrial fibrillation (PAF) is a common and potential treatable cause of cryptogenic stroke (CS). We sought to prospectively identify independent predictors of atrial fibrillation (AF) detection in patients with CS and sinus rhythm on baseline electrocardiogram (ECG), without prior AF history. We had hypothesized that cardiac arrhythmia detection during neurosonology examinations (Carotid Duplex (CDU) and Transcranial Doppler (TCD)) may be associated with higher likelihood of AF detection. Methods: Consecutive CS patients were prospectively evaluated over a six-year period. Demographics, clinical and imaging characteristics of cerebral ischemia were documented. The presence of arrhythmia during spectral waveform analysis of CDU/TCD was recorded. Left atrial enlargement was documented during echocardiography using standard definitions. The outcome event of interest included PAF detection on outpatient 24-h Holter ECG recordings. Statistical analyses were performed using univariate and multivariate logistic regression models. Results: A total of 373 patients with CS were evaluated (mean age 60 ± 11 years, 67% men, median NIHSS-score 4 points). The rate of PAF detection of any duration on Holter ECG recordings was 11% (95% CI 8%–14%). The following three variables were independently associated with the likelihood of AF detection on 24-h Holter-ECG recordings in both multivariate analyses adjusting for potential confounders: age (OR per 10-year increase: 1.68; 95% CI: 1.19–2.37; p = 0.003), moderate or severe left atrial enlargement (OR: 4.81; 95% CI: 1.77–13.03; p = 0.002) and arrhythmia detection during neurosonology evaluations (OR: 3.09; 95% CI: 1.47–6.48; p = 0.003). Conclusion: Our findings underline the potential utility of neurosonology in improving the detection rate of PAF in patients with CS. Full article

In clinical practice, empirical treatments are often offered to couples with recurrent pregnancy loss, including in vitro fertilization. Given that most patients with recurrent pregnancy loss are fertile, the scientific rationale of in vitro fertilization for these couple is debatable. This review will discuss the potential benefits of using in vitro fertilization in couples with recurrent pregnancy loss, such as shortening the time to conceive, optimizing the timing of conception, improving gamete and embryo quality, endometrial receptivity and the use of “adds-on”. At present, there is not enough evidence to justify IVF as a treatment option in couples with unexplained recurrent pregnancy loss. Full article

Hand injuries after high-pressure injection are a medical emergency. These events occur frequently in workers during industrial cleaning, painting, and lubrication, and may have devastating consequences, leading to eventual amputation and poor functional outcomes. The authors have investigated the evolution, management, and outcome. Medical records of occupational medicine units and hand surgery units were collected in order to spot the high-pressure gear accident cases. Records were analyzed by dividing the subjects into two groups: those treated within 6 h and after 6 h of the trauma. A follow-up was carried out at least 1 year after treatment; the post-treatment outcomes were assessed. Of the 71 (100%) subjects, 26 (37%) were treated ≤6 h and 45 (63%) >6 h. A total of 28% (n = 20) underwent amputation. In 61% of cases, accidents had occurred in the iron and steel sector. High viscosity materials with a delayed treatment beyond 6 h seemed to determine compartmental syndrome and following amputation. A significantly better outcome was reported among subjects treated ≤6 h compared to those treated >6 h, 20% (n = 7) versus 26% (n = 9), respectively. Early management of this type of injury is crucial. The results of this study may contribute to providing guidelines to occupational physicians in order to best manage this type of emergency. Full article

The cardioprotective effects of volatile anesthetics versus total intravenous anesthesia (TIVA) are controversial, especially in patients undergoing non-cardiac surgery. Using current generation high-sensitivity cardiac troponin (hs-cTn), we aimed to evaluate the effect of anesthetics on the occurrence of myocardial injury after non-cardiac surgery (MINS). From February 2010 to December 2016, 3555 patients without preoperative hs-cTn elevation underwent non-cardiac surgery under general anesthesia. Patients were grouped according to anesthetic agent; 659 patients were classified into a propofol-remifentanil total intravenous anesthesia (TIVA) group, and 2896 patients were classified into a volatile group. To balance the use of remifentanil between groups, a balanced group (n = 1622) was generated with patients who received remifentanil infusion in the volatile group, and two separate comparisons were performed (TIVA vs. volatile and TIVA vs. balanced). The primary outcome was occurrence of MINS, defined as rise of hs-cTn I ≥ 0.04 ng/mL within postoperative 48 hours. The secondary outcomes were 30-day mortality, postoperative acute kidney injury (AKI), and adverse events during hospital stay (mortality, type I myocardial infarction (MI), and new-onset arrhythmia). In propensity-matched analyses, the occurrence of MINS was lower in the TIVA group compared to the volatile group (OR 0.642; 95% CI 0.450–0.914; p = 0.014). However, after balancing the use of remifentanil, there was no difference between groups in the risk of MINS (OR 0.832; 95% CI 0.554–1.251; p-value = 0.377). There were no significant associations between the two groups in type 1 MI, new-onset atrial fibrillation, in-hospital and 30-day mortality before and after balancing the use of remifentanil. However, the incidence of postoperative AKI was lower in the TIVA group (OR 0.362; 95% CI 0.194–0.675; p-value = 0.001). After balancing the use of remifentanil, volatile anesthesia and TIVA showed comparable effects on MINS in patients undergoing non-cardiac surgery without preoperative myocardial injury. Further studies are needed on the benefit of remifentanil infusion. Full article

Background: Research has suggested that bone fractures can hinder the health status of patients’ life. However, limited research has examined the impact that the healing process of a fracture has on the physical health and psychological state of individuals, particularly in considering the short- and long-term impact of having a fracture that fails to heal and drops into a non-union. The aim of this systematic review is to better understand the impact of fracture non-union to physical health and to respective psychological outcomes. Methods: Electronic databases ‘PubMed’, ‘Cochrane’, ‘PsycInfo’, ‘Medline’, ‘Embase’, ‘Web of Science’, and ‘CINAHL’ were used. Search terms used were nonunion OR non-union OR “non union” OR “long bone” OR “delayed union” AND “quality of life” OR qol OR depression OR anxiety OR psycholog* OR PTSD OR “post-traumatic stress disorder”. Studies published in the years 1995 to 2018 were included. Two independent reviewers carried out screening and data extraction. Studies were included if (1) participants were adult (human) patients with a traumatic non-union secondary to fracture/s; (2) outcomes measured included physical health and psychological wellbeing (e.g., PTSD, psychological trauma, depression, anxiety, etc.). Studies received emphasis if they compared those outcomes between: (1) The “non-union” group to a normative, matched population and (2) the “non-union group” to the same group after union was achieved. However, studies that did not use comparison groups were also included. Results: Out of the 1896 papers identified from our thorough literature search, 13 met the inclusion criteria. Quality assessment was done by the Methodological Index for Non-Randomized Studies (MINORS). Findings suggested that non-unions had a detrimental impact on physical health, and psychological difficulties often after recovery. Conclusions: Patients who experience a long bone non-union are at risk of greater psychological distress and lower physical health status. There is a need for early identification of psychological distress in patients with fracture non-unions and psychological provision should become part of the available treatment. Full article

In the United States, one out of every 500 African American children have sickle cell disease (SCD), and SCD affects approximately 100,000 Americans. Significant advances in the treatment of this monogenetic disorder have failed to substantially extend the life expectancy of adults with SCD over the past two decades. Hematopoietic stem cell transplantation (HSCT) remains the only curative option for patients with SCD. While human leukocyte antigen (HLA) matched sibling HSCT has been successful, its availability is extremely limited. This review summarizes various conditioning regimens that are currently available. We explore recent efforts to expand the availability of allogeneic HSCT, including matched unrelated, umbilical cord blood, and haploidentical stem cell sources. We consider the use of nonmyeloablative conditioning and haploidentical donor sources as emerging strategies to expand transplant availability, particularly for SCD patients with complications and comorbidities who can undergo neither matched related transplant nor myeloablative conditioning. Finally, we show that improved conditioning agents have improved success rates not only in the HLA-matched sibling setting but also alternative donor settings. Full article

Spinal stenosis is a common condition in elderly individuals. Many patients are unresponsive to the conventional treatment. If the transforaminal epidural block does not exert a sufficient treatment effect, percutaneous transforaminal epidural adhesiolysis (PTFA) through the safe-triangle approach using an inflatable balloon catheter can reduce the patients’ pain and improve their functional capacity. We aimed to evaluate the safety and efficacy of the Kambin’s-triangle approach for PTFA using an inflatable balloon catheter and compare this approach to the traditional safe-triangle approach. Thirty patients with chronic unilateral L5 radiculopathy were divided into two groups: the safe-triangle-approach and Kambin’s-triangle-approach groups, with 15 patients each. The success rate of the procedure was assessed. Pain and dysfunction were assessed using the Numerical Rating Scale and Oswestry Disability Index, respectively, before the procedure and at 1 and 3 months after the procedure. The success rate of the procedure was high in both the groups, with no significant difference between the groups. The Numerical Rating Scale and Oswestry Disability Index scores significantly decreased 3 months after the procedure in both the groups, with no significant difference between the groups. For patients in whom the safe-triangle approach for PTFA is difficult, the Kambin’s-triangle approach could be an alternative. Full article

Exosome-like extracellular vesicles (ELVs) contain biomolecules that have potential as diagnostic biomarkers, such as proteins, micro-RNAs (miRNAs), and lipids. However, it is difficult to enrich ELVs consistently with high yield and purity from clinical samples, which hampers the development of ELV biomarkers. This is particularly true for miRNAs in protein-rich plasma. Hence, we modified ELV isolation protocols of three commercially available polymer-precipitation-based kits using proteinase K (PK) treatment to quantify ELV-associated miRNAs in human plasma. We compared the yield, purity, and characteristics of enriched plasma ELVs, and measured the relative quantity of three selected miRNAs (miR-30c, miR-126, and miR-192) in ELVs using six human plasma samples. Compared with the original protocols, we demonstrated that ELVs can be isolated with PK treatment with high purity (i.e., lack of non-exosomal proteins and homogeneous size of vesicles) and yield (i.e., abundancy of exosomal markers), which were dependent on kits. Using the kit with the highest purity and yield with PK treatment, we successfully quantified ELV miRNAs (levels of 45%–65% in total plasma) with acceptable variability. Collectively, ELV enrichment using the modified easy-to-use method appears suitable for the analysis of miRNAs, although its clinical applicability needs to be confirmed in larger clinical studies. Full article