Ongoing outbreak of pneumonia caused by novel coronavirus (2019-nCoV) began in December 2019 in Wuhan, China, and the number of new patients continues to increase. Even though it began to spread to many other parts of the world, such as other Asian countries, the Americas, Europe, and the Middle East, the impact of secondary outbreaks caused by exported cases outside China remains unclear. We conducted simulations to estimate the impact of potential secondary outbreaks in a community outside China. Simulations using stochastic SEIR model were conducted, assuming one patient was imported to a community. Among 45 possible scenarios we prepared, the worst scenario resulted in the total number of persons recovered or removed to be 997 (95% CrI 990–1000) at day 100 and a maximum number of symptomatic infectious patients per day of 335 (95% CrI 232–478). Calculated mean basic reproductive number (R₀) was 6.5 (Interquartile range, IQR 5.6–7.2). However, better case scenarios with different parameters led to no secondary cases. Altering parameters, especially time to hospital visit. could change the impact of a secondary outbreak. With these multiple scenarios with different parameters, healthcare professionals might be able to better prepare for this viral infection. Full article

Background: Scapula body fractures are rare injuries with an incidence of 1% of all fractures accounting for 3% to 5% of all upper extremity fractures. Fractures of the scapula commonly result from high-energetic trauma and fall from great height. While several studies focused on concomitant injuries of chest and head as well as the cervical spine, up to now in the common literature, no study exists analyzing the prevalence of concomitant intra-articular glenohumeral injury following extra-articular scapular fracture. Objectives: The aim of this study was to analyze the prevalence of concomitant intra-articular glenohumeral injuries in acute fractures of the scapula by performing magnetic resonance imaging (MRI) of the shoulder joint. Study Design and Methods: This prospective cohort study was performed at our academic Level I trauma center from November 2014 to October 2016. According to our clinical algorithm, all patients suffering from an acute scapula body fracture primarily underwent computed tomography (CT) for assigning the fracture according to the Orthopedic Trauma Association (OTA)-classification and therapy planning. In addition, 3 T MRI-scans of all patients were performed within seven days after trauma. Results: Twenty-one (16 male/5 female, mean age 53 years (25–83 y) patients with scapula body fractures (OTA 14.A3.2 80.1%, OTA 14.A3.1 4.8%, OTA14.B3.1 4.8%, OTA14.C3 9.5%) were enrolled. MRI revealed 11 acute intra-articular injuries in 8 of 21 patients (38%). In all 21 patients, hematoma of the rotator cuff and periarticular muscles was present. Three patients (14.3%) presented a partial bursa sided tear of the supraspinatus tendon, whereas in 5 (23.8%), a partial articular sided supraspinatus tendon tear and in 2 (9.5%) patients, a subtotal tear was observed. One patient (4.8%) showed a complete transmural supraspinatus tendon tear. Conclusions: Traumatic concomitant glenohumeral injuries in scapula body fractures seem to be more frequent than generally expected. Subsequent surgical treatment of these formerly missed but therapy-relevant injuries may increase functional outcome and reduce the postoperative complication rate following scapula body fractures. Full article

The optimal range of serum uric acid (urate) associated with the lowest risk for developing cardiometabolic diseases is unknown in a generally healthy population. This 5-year cohort study is designed to identify the optimal range of serum urate. The data were collected from 13,070 Japanese between ages 30 and 85 at the baseline (2004) from the Center for Preventive Medicine, St. Luke’s International Hospital, Tokyo. We evaluated the number of subjects (and prevalence) of those free of the following conditions: hypertension, diabetes, dyslipidemia, and chronic kidney disease (CKD) over 5 years for each 1 mg/dL of serum urate stratified by sex. Furthermore, the odds ratios (ORs) for remaining free of these conditions were calculated with multiple adjustments. Except for truly hypouricemic subjects, having lower serum urate was an independent factor for predicting the absence of hypertension, dyslipidemia, and CKD, but not diabetes. The OR of each 1 mg/dL serum urate decrease as a protective factor for hypertension, dyslipidemia, and CKD was 1.153 (95% confidence interval, 1.068–1.245), 1.164 (1.077–1.258), and 1.226 (1.152–1.306) in men; 1.306 (1.169–1.459), 1.121 (1.022–1.230), and 1.424 (1.311–1.547) in women, respectively. Moreover, comparing serum urate of 3–5 mg/dL in men and 2–4 mg/dL in women, hypouricemia could be a higher risk for developing hypertension (OR: 4.532; 0.943–21.78) and CKD (OR: 4.052; 1.181–13.90) in women, but not in men. The optimal serum urate range associated with the lowest development of cardiometabolic diseases was less than 5 mg/dL for men and 2–4 mg/dL for women, respectively. Full article

A growing body of literature on the 2019 novel coronavirus (SARS-CoV-2) is becoming available, but a synthesis of available data has not been conducted. We performed a scoping review of currently available clinical, epidemiological, laboratory, and chest imaging data related to the SARS-CoV-2 infection. We searched MEDLINE, Cochrane CENTRAL, EMBASE, Scopus and LILACS from 01 January 2019 to 24 February 2020. Study selection, data extraction and risk of bias assessment were performed by two independent reviewers. Qualitative synthesis and meta-analysis were conducted using the clinical and laboratory data, and random-effects models were applied to estimate pooled results. A total of 61 studies were included (59,254 patients). The most common disease-related symptoms were fever (82%, 95% confidence interval (CI) 56%–99%; n = 4410), cough (61%, 95% CI 39%–81%; n = 3985), muscle aches and/or fatigue (36%, 95% CI 18%–55%; n = 3778), dyspnea (26%, 95% CI 12%–41%; n = 3700), headache in 12% (95% CI 4%–23%, n = 3598 patients), sore throat in 10% (95% CI 5%–17%, n = 1387) and gastrointestinal symptoms in 9% (95% CI 3%–17%, n = 1744). Laboratory findings were described in a lower number of patients and revealed lymphopenia (0.93 × 10⁹/L, 95% CI 0.83–1.03 × 10⁹/L, n = 464) and abnormal C-reactive protein (33.72 mg/dL, 95% CI 21.54–45.91 mg/dL; n = 1637). Radiological findings varied, but mostly described ground-glass opacities and consolidation. Data on treatment options were limited. All-cause mortality was 0.3% (95% CI 0.0%–1.0%; n = 53,631). Epidemiological studies showed that mortality was higher in males and elderly patients. The majority of reported clinical symptoms and laboratory findings related to SARS-CoV-2 infection are non-specific. Clinical suspicion, accompanied by a relevant epidemiological history, should be followed by early imaging and virological assay. Full article

Poly (ADP-ribose) polymerase inhibitors (PARPi) have proven to be beneficial to patients with metastatic breast cancer with BRCA1/2 (BReast CAncer type 1 and type 2 genes) mutations. However, certain PARPi in pre-clinical studies have been shown to inhibit cell growth and promote the death of breast cancer cells lacking mutations in BRCA1/2. Here, we examined the inhibitory potency of 13 different PARPi in 12 breast cancer cell lines with and without BRCA-mutations using cell viability assays. The results showed that 5 of the 8 triple-negative breast cancer (TNBC) cell lines were susceptible to PARPi regardless of the BRCA-status. The estrogen receptor (ER) negative/ human epidermal growth factor receptor 2 (HER2) positive (ER-/HER2+) cells, SKBR3 and JIMT1, showed high sensitivity to Talazoparib. Especially JIMT1, which is known to be resistant to trastuzumab, was responsive to Talazoparib at 0.002 µM. Niraparib, Olaparib, and Rucaparib also demonstrated effective inhibitory potency in both advanced TNBC and ER-/HER2+ cells with and without BRCA-mutations. In contrast, a BRCA-mutant TNBC line, HCC1937, was less sensitive to Talazoparib, Niraparib, Rucaparib, and not responsive to Olaparib. Other PARPi such as UPF1069, NU1025, AZD2461, and PJ34HCl also showed potent inhibitory activity in specific breast cancer cells. Our data suggest that the benefit of PARPi therapy in breast cancer is beyond the BRCA-mutations, and equally effective on metastatic TNBC and ER-/HER2+ breast cancers. Full article

Objectives. The aim of this study is to provide information about prevalence, etiology, risk factors, clinical characteristics and endoscopic features of various types of infectious esophagitis in children. Methods. We performed a total of 520 upper gastrointestinal tract endoscopies in Pediatric Clinic II, Emergency Hospital for Children, Cluj-Napoca. Indications for endoscopy in our cohort were gastrointestinal tract symptoms such as dysphagia, heartburn, or appetite loss. Results. The prevalence of infectious esophagitis in the study population was 2.11% (11 patients). Candida albicans (C. albicans) was the most frequent cause. Our data illustrates that herpes simplex virus (HSV)-induced esophagitis is common in immunocompromised patients and should be systematically suspected in cases of severe dysphagia, heartburn, or hematemesis. In the present study, all cytomegalovirus (CMV) esophagitis patients were immunocompromised. Immunodeficiency (81.8%) and prolonged antibiotic therapy with broad-spectrum antibiotics were by far the most important risk factors involved in the pathogenicity of the disease. Dysphagia, appetite loss, heartburn, epigastralgia, and hematemesis were the main clinical manifestations. Infectious esophagitis was associated with significant mortality. In four patients, endoscopy during life showed signs of infectious esophagitis; however, the precise etiology was only established post-mortem, in the pathological anatomy laboratory department. A risk factor involved in pathogenesis of post-mortem diagnosed infectious esophagitis is the DiGeorge syndrome for CMV and HSV patients. Conclusions. The study illustrates that infectious esophagitis should be considered in immunocompromised infants with prolonged antibiotic therapy with broad-spectrum antibiotics. Full article

Background: Concomitant left main coronary artery (LMCA) disease in patients with chronic total occlusions (CTO) commonly results in referral for coronary artery bypass grafting, although the impact of LMCA in CTO patients remains largely unknown. Nevertheless, patient selection for percutaneous coronary intervention of CTOs (CTO-PCI) or alternative revascularization strategies should be based on precise evaluation of the coronary anatomy to anticipate those patients that most likely benefit from a procedure and not on strict adherence to perpetual clinical practice. Therefore, the aim of this study was to assess the impact of LMCA disease on long-term outcomes in patients undergoing percutaneous coronary intervention for CTO. Methods: We enrolled 3860 consecutive patients undergoing PCI for at least one CTO lesion and investigated the predictive value of concomitant LMCA disease. All-cause mortality was defined as the primary study endpoint. Results: We observed that LMCA disease is significantly associated with mortality. In the Cox regression analysis, we observed a crude hazard ratio (HR) 1.59 (95% confidence interval (CI) 1.23–2.04, p < 0.001) for patients with LMCA disease as compared to patients without. Results remained unchanged after bootstrap- or clinical confounder-based adjustment. Conclusion: LMCA disease is associated with excess mortality in CTO patients. Specifically, anatomical features such as CTO of the circumflex artery represent a high risk patient population. Full article

Nonalcoholic fatty liver disease (NAFLD) emerges as an important global burden and Helicobacter pylori infection (Hp-I) has been suggested as a risk factor of NAFLD, although controversy exists. This retrospective study aimed to investigate a potential impact of active Hp-I on NAFLD severity in morbidly obese patients, subjected to bariatric surgery and gastric biopsy for documentation of Hp-I. Of 64 eligible participants, 15 (23.4%) were diagnosed with active Hp-I, showing higher rates of nonalcoholic steatohepatitis (NASH) than those without Hp-I (86.7% vs. 26.5%, respectively; p < 0.001). Concerning histological lesions, steatosis grade (p = 0.027), ballooning (p < 0.001), lobular inflammation (p = 0.003), and fibrosis stage (p < 0.001) were also more severe in Hp-I positive patients. Likewise, liver function tests, insulin resistance, dyslipidemia, and arterial hypertension were significantly higher in Hp-I positive patients. Hp-I was independently positively associated with NASH (beta = 3.27; p = 0.002), severe NASH (beta = 2.37; p = 0.018), and the presence of fibrosis (beta = 3.86; p = 0.001) in a binary regression model, after adjustment for potential confounders. In conclusion, active Hp-Ι was independently associated with NASH and fibrosis, findings offering potential clinical implication. Full article

Background: The pleomorphic clinical presentation makes the diagnosis of desminopathy difficult. We aimed to describe the prevalence, phenotypic expression, and mitochondrial function of individuals with putative disease-causing desmin (DES) variants identified in patients with an unexplained etiology of cardiomyopathy. Methods: A total of 327 Czech patients underwent whole exome sequencing and detailed phenotyping in probands harboring DES variants. Results: Rare, conserved, and possibly pathogenic DES variants were identified in six (1.8%) probands. Two DES variants previously classified as variants of uncertain significance (p.(K43E), p.(S57L)), one novel DES variant (p.(A210D)), and two known pathogenic DES variants (p.(R406W), p.(R454W)) were associated with characteristic desmin-immunoreactive aggregates in myocardial and/or skeletal biopsy samples. The individual with the novel DES variant p.(Q364H) had a decreased myocardial expression of desmin with absent desmin aggregates in myocardial/skeletal muscle biopsy and presented with familial left ventricular non-compaction cardiomyopathy (LVNC), a relatively novel phenotype associated with desminopathy. An assessment of the mitochondrial function in four probands heterozygous for a disease-causing DES variant confirmed a decreased metabolic capacity of mitochondrial respiratory chain complexes in myocardial/skeletal muscle specimens, which was in case of myocardial succinate respiration more profound than in other cardiomyopathies. Conclusions: The presence of desminopathy should also be considered in individuals with LVNC, and in the differential diagnosis of mitochondrial diseases. Full article

Trastuzumab in combination with a platinum and fluorouracil is the treatment of choice for patients with advanced human epidermal growth factor receptor 2 (HER2) positive gastric cancer and gastroesophageal junction (GEJ) cancer. Pathological assessment of the HER2 status in gastric/GEJ cancer, however, still remains difficult. However, it is a crucial prerequisite for optimal treatment. The GASTRIC-5 registry was designed as an observational, multi-center research initiative comparing local and central HER2 testing. HER2 status was assessed by immunohistochemistry (IHC) and in equivocal cases (IHC score 2+) by additional in-situ hybridization. Between May 2011 and August 2018, tumor samples of 183 patients were tested in local and central pathology laboratories, respectively. Central testing revealed HER2 positivity in 38 samples (21%). Discordant HER2 results were found in 12% (22 out of 183) with locally HER2 positive/centrally HER2 negative results (9%, 17 out of 183), exceeding locally HER2 negative/centrally HER2 positive results (3%, 5 out of 183). Centrally confirmed HER2 positive patients receiving trastuzumab-based palliative first-line therapy showed a longer median overall survival compared to centrally HER2 positive patients not receiving trastuzumab (17.7 months (95% CI: 10,870–24,530) vs. 6.9 months (95% CI: 3.980–9.820), p = 0.016). The findings of the GASTRIC-5 registry corroborate the challenge of HER2 testing in gastric/GEJ cancer and highlight the necessity for central quality control to optimize individual treatment options. Centrally HER2 positive patients not receiving trastuzumab had the worst outcome in a Western real-world gastric/GEJ cancer cohort. Full article

The outcome of patients with hepatocellular carcinoma (HCC) is still poor. Decorin is a small leucine-rich proteoglycan, which exerts antiproliferative and antiangiogenic properties in vitro. We aimed to investigate the associations of decorin with physical function and prognosis in patients with HCC. We enrolled 65 patients with HCC treated with transcatheter arterial chemoembolization (median age, 75 years; female/male, 25/40). Serum decorin levels were measured using enzyme-linked immunosorbent assays; patients were classified into the High or Low decorin groups by median levels. Associations of decorin with physical function and prognosis were evaluated by multivariate correlation and Cox regression analyses, respectively. Age and skeletal muscle indices were not significantly different between the High and Low decorin groups. In the High decorin group, the 6-min walking distance was significantly longer than the Low decorin group and was significantly correlated with serum decorin levels (r = 0.2927, p = 0.0353). In multivariate analysis, the High decorin group was independently associated with overall survival (hazard ratio 2.808, 95% confidence interval 1.016–8.018, p = 0.0498). In the High decorin group, overall survival rate was significantly higher than in the Low decorin group (median 732 days vs. 463 days, p = 0.010). In conclusion, decorin may be associated with physical function and prognosis in patients with HCC. Full article

Background: the study of paraspinal muscles is pivotal for the diagnosis and staging of Amyotrophic Lateral Sclerosis (ALS), and is usually performed by electromyography. Objective: to evaluate the role of paraspinal muscle MRI as a diagnostic biomarker in ALS. Methods: we evaluated T1-w images of newly diagnosed ALS patients (n = 14), age-matched healthy controls (n = 11), patients affected by inflammatory myopathy (n = 10), and lumbar radiculopathy (n = 19), and compared them semiquantitatively by using the Mercuri Scale. Results: a significant difference in the appearance of the psoas muscle was observed between ALS patients and patients with radiculopathy (p = 0.003); after stratifying ALS patients into spinal and bulbar onsets, we found a significant difference in the appearance of the longissimus dorsi muscle between the spinal onset ALS subgroup and bulbar onset ALS subgroup (p = 0.0245), while no difference was found for multifidus (p = 0.1441), iliocostal (p = 0.0655), and psoas muscles (p = 0.0813) between the cohort subgroups. Conclusions: paraspinal T1-w MRI could help to distinguish spinal ALS patients from healthy and pathological controls. Specifically, the study of longissimus dorsi could play the role of a diagnostic ALS biomarker. Full article

Aim: Evidence on non-ischemic cardiogenic shock (CS) is scarce. The aim of this study was to investigate differences in patient characteristics, use of treatments and outcomes in patients with non-ischemic vs. ischemic CS. Methods: Patients with CS admitted between October 2009 and October 2017 were identified and stratified as non-ischemic/ischemic CS based on the absence/presence of acute myocardial infarction. Logistic/Cox regression models were fitted to investigate the association between non-ischemic CS and patient characteristics, use of treatments and 30-day in-hospital mortality. Results: A total of 978 patients were enrolled in this study; median age was 70 (interquartile range 58, 79) years and 70% were male. Of these, 505 patients (52%) had non-ischemic CS. Patients with non-ischemic CS were more likely to be younger and female; were less likely to be active smokers, to have diabetes or decreased renal function, but more likely to have a history of myocardial infarction; and they were more likely to present with unfavorable hemodynamics and with mechanical ventilation. Regarding treatments, patients with non-ischemic CS were more likely to be treated with catecholamines, but less likely to be treated with extracorporeal membrane oxygenation or percutaneous left-ventricular assist devices. After adjustment for multiple relevant confounders, non-ischemic CS was associated with a significant increase in the risk of 30-day in-hospital mortality (hazard ratio 1.14, 95% confidence interval 1.04–1.24, p < 0.01). Conclusion: In this large study, non-ischemic CS accounted for more than 50% of all CS cases. Non-ischemic CS was not only associated with relevant differences in patient characteristics and use of treatments, but also with a worse prognosis. These findings highlight the need for effective treatment strategies for patients with non-ischemic CS. Full article

The frontline treatment options for patients with metastatic renal cell carcinoma (mRCC) are evolving rapidly since the approval of combination immunotherapies by the U.S. Food and Drug Administration (USFDA) and the European Medicines Agency (EMA). In particular, in combination with vascular endothelial growth factor receptor (VEGFR) tyrosine-kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs) have significantly improved the outcome of patients with mRCC compared to TKI monotherapy. Here, we review the preclinical data supporting the combination of ICIs with VEGFR TKIs. The VEGF-signaling inhibition could ideally sustain immunotherapy through a positive modulation of the tumor microenvironment (TME). Antiangiogenetics, in fact, with their inhibitory activity on myelopoiesis that indirectly reduces myeloid-derived suppressor cells (MDSCs) and regulatory T cells’ (Tregs) frequency and function, could have a role in determining an effective anti-tumor immune response. These findings are relevant for the challenges posed to clinicians concerning the clinical impact on treatment strategies for mRCC. Full article

Objective: To evaluate a panel of salivary analytes involving biomarkers of inflammation, stress, immune system and antioxidant status in patients with burning mouth syndrome (BMS) and to study their relationship with clinical variables. Materials and Methods: A total of 51 patients with BMS and 31 controls were consecutively enrolled in the study, with the recording of oral habits, the severity of pain using a visual analogue scale (VAS), the Hospital Anxiety and Depression (HAD) score and the Oral Health Impact Profile-14 (OHIP14) score. Resting whole saliva was collected with the drainage technique, followed by the measurement of 11 biomarkers. Results: The salivary flow was higher in patients with BMS. Among all the biomarkers studied, significantly higher levels of alpha-amylase, immunoglobulin A (IgA), and macrophage inflammatory protein-4 (MIP4) and lower levels of uric acid and ferric reducing activity of plasma (FRAP) were observed in the saliva of patients with BMS as compared to the controls (p < 0.05 in all cases). Positive correlations were found between pain, oral quality of life and anxiety scores and salivary biomarkers. Conclusions: BMS is associated with changes in salivary biomarkers of inflammation, oxidative stress and stress, being related to the degree of pain and anxiety. Full article