Malignant peripheral nerve sheath tumor (MPNST) is a rare type of soft tissue sarcomas. The localized disease is usually treated with surgery along with perioperative chemo- or radiotherapy. However, up to 70% of patients can develop distant metastases. The study aimed to evaluate the modes and outcomes of systemic treatment of patients with diagnosed MPNST treated in a reference center. In total, 115 patients (56 female and 59 male) diagnosed with MPNST and treated due to unresectable or metastatic disease during 2000–2019 were included in the retrospective analysis. Schemes of systemic therapy and the outcomes—progression-free survival (PFS) and overall survival (OS)—were evaluated. The median PFS in the first line was 3.9 months (95% CI 2.5–5.4). Doxorubicin-based regimens were the most commonly used in the first line (50.4% of patients). There were no significant differences in PFS between chemotherapy regimens most commonly used in the first line (p = 0.111). The median OS was 15.0 months (95% CI 11.0–19.0) and the one-year OS rate was 63%. MPNST are resistant to the majority of systemic therapies, resulting in poor survival in advanced settings. Chemotherapy with doxorubicin and ifosfamide is associated with the best response and longest PFS. Future studies and the development of novel treatment options are necessary for the improvement of treatment outcomes. Full article

Early studies of deep brain stimulation (DBS) for various neurological disorders involved a temporary trial period where implanted electrodes were externalized, in which the electrical contacts exiting the patient’s brain are connected to external stimulation equipment, so that stimulation efficacy could be determined before permanent implant. As the optimal brain target sites for various diseases (i.e., Parkinson’s disease, essential tremor) became better established, such trial periods have fallen out of favor. However, deep brain stimulation trial periods are experiencing a modern resurgence for at least two reasons: (1) studies of newer indications such as depression or chronic pain aim to identify new targets and (2) a growing interest in adaptive DBS tools necessitates neurophysiological recordings, which are often done in the peri-surgical period. In this review, we consider the possible approaches, benefits, and risks of such inpatient trial periods with a specific focus on developing new DBS therapies for chronic pain. Full article

The impact of migraine on postoperative nausea and vomiting (PONV) is controversial, and few studies have focused on their relationship. Thus, we investigated the impact of migraine, among other risk factors, on PONV in a large retrospective study. We analyzed 10 years of clinical data from the Smart Clinical Data Warehouse of Hallym University Medical Center. PONV was defined as nausea or vomiting within the first 24 h after surgery. Patients diagnosed by a neurologist and with a history of triptan use before surgery were enrolled into the migraine group. We enrolled 208,029 patients aged > 18 years who underwent general anesthesia (GA), among whom 19,786 developed PONV within 24 h after GA and 1982 had migraine. Before propensity score matching, the unadjusted and fully adjusted odds ratios (ORs) for PONV in subjects with versus without migraine were 1.52 (95% confidence interval (CI), 1.34–1.72; p < 0.001) and 1.37 (95% CI, 1.21–1.56; p < 0.001), respectively. The OR for PONV in patients with migraine was also high (OR, 1.37; 95% CI, 1.13–1.66; p = 0.001) after matching. Our findings suggest that migraine is a significant risk factor for PONV. Full article

(1) Background: Tumor hypoxia leads to metastasis and certain immune responses, and interferes with normal biological functions. It also affects glucose intake, down-regulates oxidative phosphorylation, and inhibits fatty-acid desaturation regulated by hypoxia-inducible factor 1α (HIF-1α). Although tumor hypoxia has been found to promote tumor metastasis, the roles of HIF-1α-regulated genes and their application are not completely integrated in clinical practice. (2) Methods: We examined the correlation between HIF-1α, metadherin (MTDH), and interleukin (IL)-10 mRNA expression, as well as their expression patterns in the prognosis of breast cancer using the Gene Expression Profiling Interactive Analysis (GEPIA) databases via a web interface; tissue microarrays (TMAs) were stained for MTDH and IL-10 protein expression using immunohistochemistry. (3) Results: HIF-1α, MTDH, and IL-10 mRNA expression are highly correlated and strongly associated with poor prognosis. MTDH and IL-10 protein expression of breast cancer patients usually harbored negative estrogen receptor (ER) or progesterone receptor (PR) status, and late-stage tumors have higher IL-10 expression. With regard to MTDH and IL-10 protein expression status for using univariate and multivariate analysis, the results showed that the protein expression of MTDH and IL-10 in ER-negative or PR-negative breast cancer patients have the worse prognosis. (4) Conclusions: we propose a new insight into hypoxia tumors in the metabolism and immune evidence for breast cancer therapy. Full article

Objectives: In our study, we evaluated and compared the prognostic value and performance of the 6th, 7th, and 8th editions of the American Joint Committee on Cancer (AJCC) staging system in patients undergoing surgery for perihilar cholangiocarcinoma (PHC). Methods: Patients undergoing liver surgery with curative intention for PHC between 2002 and 2019 were identified from a prospective database. Histopathological parameters and stage of the PHC were assessed according to the 6th, 7th, and 8th editions of the tumor node metastasis (TNM) classification. The prognostic accuracy between staging systems was compared using the area under the receiver operating characteristic curve (AUC) model. Results: Data for a total of 95 patients undergoing liver resection for PHC were analyzed. The median overall survival time was 21 months (95% CI 8.1–33.9), and the three- and five-year survival rates were 46.1% and 36.2%, respectively. Staging according to the 8th edition vs. the 7th edition resulted in the reclassification of 25 patients (26.3%). The log-rank p-values for the 7th and 8th editions were highly statistically significant (p ≤ 0.01) compared to the 6th edition (p = 0.035). The AJCC 8th edition staging system showed a trend to better discrimination, with an AUC of 0.69 (95% CI: 0.52–0.84) compared to 0.61 (95% CI: 0.51–0.73) for the 7th edition. Multivariate survival analysis revealed male gender, age >65 years, positive resection margins, presence of distant metastases, poorly tumor differentiation, and lymph node involvement, such as no caudate lobe resection, as independent predictors of poor survival (p < 0.05). Conclusions: In the current study, the newly released 8th edition of AJCC staging system showed no significant benefit compared to the previous 7th edition in predicting the prognosis of patients undergoing liver resection for perihilar cholangiocarcinoma. Further research may help to improve the prognostic value of the AJCC staging system for PHC—for instance, by identifying new prognostic markers or staging criteria, which may improve that individual patient’s outcome. Full article

Virtual reality (VR), a technology that provides a stimulated sensory experience, has recently been implemented in various fields of medicine. Several studies have investigated the efficacy of VR on preoperative anxiety. The purpose of this meta-analysis was to validate whether VR could relieve preoperative anxiety in patients undergoing surgery. Electronic databases were searched to identify all randomized controlled trials (RCTs) investigating the effect of VR on preoperative anxiety. The primary outcome was defined as the preoperative anxiety scores. We estimated the effect size using the standard mean difference (SMD) with a 95% confidence interval (CI) using a random effect model. Ultimately, 10 RCTs, with a total of 813 patients, were included in the final analysis. Preoperative anxiety was significantly lower in the VR group than in the control group (SMD −0.64, 95% CI −1.08 to −0.20, p = 0.004). In a subgroup analysis, the preoperative anxiety scores were lower in the VR group than in the control group in pediatric patients (SMD −0.71, 95% CI −1.14 to −0.27, p = 0.002), whereas a significant difference was not observed between the two groups in adult patients (p = 0.226). The results of this meta-analysis indicated that VR could decrease preoperative anxiety, especially in pediatric patients. Full article

An increasing number of total knee replacements (TKRs) are being performed in response to the growing burden of osteoarthritis. Patients <65 years of age represent the fastest growing group of TKR recipients and are expected to account for an increasing number of primary and revision procedures. Concerns have been raised about the outcomes that can be expected by this age demographic who are more active, physically demanding, and have longer life expectancies compared to older TKR recipients. This systematic review and meta-analysis evaluated the effectiveness of TKR for osteoarthritis in patients <65 years of age, compared to older individuals. A systematic search of Embase and Medline was conducted to identify studies which examined patient-reported outcomes measured using disease-specific and generic health-related quality of life instruments. Ten studies met our inclusion criteria and were included in this review. These studies comprised 1747 TKRs performed between 1977 and 2014. In the meta-analysis of two prospective studies (288 TKRs), patients <65 years of age were able to attain large and clinically meaningful improvements in pain, function, and quality of life. One of these studies (61 TKRs) suggested that patients <55 years of age attained a larger degree of improvement compared to older individuals. Results into the second postoperative decade were less certain, with some data suggesting a high prevalence of pain and patterns of functional decline. Further research is required to investigate longer-term outcomes following TKR for osteoarthritis in younger patients. Full article

In this cross-sectional observational study, we investigated the relationship between photoreceptor layer disruption and telangiectasia in patients diagnosed with early stage macular telangiectasia type 2 (MacTel). A total of 31 eyes (17 patients) with MacTel were imaged with adaptive optics scanning laser ophthalmoscopy (AOSLO) and optical coherence tomography angiography (OCTA). Confocal AOSLO was used to visualize dark regions of nonwaveguiding outer segments, which we refer to as “photoreceptor lesions”. En-face OCTA images of the deep capillary plexus (DCP) were used in conjunction with confocal AOSLO to evaluate the topographic relationship between areas of capillary telangiectasias and photoreceptor lesions. Among seven eyes with early stage MacTel (stage 0–2 based on OCT), we identified ten photoreceptor lesions, all of which were located within parafoveal quadrants containing DCP telangiectasia on OCTA. Seven of the lesions corresponded to the intact ellipsoid zone on spectral-domain OCT (SD-OCT), and three of these also corresponded to the intact interdigitation zone. This work demonstrates a topographic relationship between AOSLO photoreceptor lesions and DCP telangiectasias, and it also suggests that these lesions with normal SD-OCT appearance may represent areas of photoreceptors at risk for dysfunction. Thus, confocal AOSLO may have a meaningful role in detecting early photoreceptor abnormalities in eyes with MacTel. Full article

Describing the characteristics of COVID-19 patients in the hospital is of importance to assist in the management of hospital capacity in the future. Here, we analyze the trajectories of 1321 patients admitted to hospitals in northern and eastern France. We found that the time from onset to hospitalization decreased with age, from 7.3 days in the 20–65 year-olds to 4.5 in the >80 year-olds (p < 0.0001). Overall, the length of stay in the hospital was 15.9 days, and the death rate was 20%. One patient out of four was admitted to the intensive care unit (ICU) for approximately one month. The characteristics of trajectories changed with age: fewer older patients were admitted to the ICU and the death rate was larger in the elderly. Admission shortly after onset was associated with increased mortality (odds-ratio (OR) = 1.8, Confidence Interval (CI) 95% [1.3, 2.6]) as well as male sex (OR = 2.1, CI 95% [1.5, 2.9]). Time from admission within the hospital to the transfer to ICU was short. The age- and sex-adjusted mortality rate decreased over the course of the epidemic, suggesting improvement in care over time. In the SARS-CoV-2 epidemic, the urgent need for ICU at admission and the prolonged length of stay in ICU are a challenge for bed management and organization of care. Full article

Diagnosis of non-IgE mediated food allergy presents a special challenge due to lack of a single, non-invasive diagnostic method. We selected three fecal biomarkers of allergic inflammation of gastrointestinal origin in order to improve the diagnostic process. Twenty-seven infants with symptoms of hematochezia were prospectively enrolled into this study. All patients underwent a complete differential diagnosis of rectal bleeding. Non-IgE mediated food allergy was confirmed by an open, oral food challenge. The control group included twenty-five infants with functional gastrointestinal disorders. Eosinophil-derived neurotoxin (EDN), tumor necrosis factor alpha (TNFα), and calprotectin concentration were measured in stools of all children by enzyme-linked immunosorbent assays (ELISA) using commercial kits. Median eosinophil-derived neurotoxin and calprotectin fecal levels were significantly higher in the study group than in the control group (p < 0.05). The difference of fecal tumor necrosis factor alpha concentration between both groups was not statistically significant (p > 0.05). The best diagnostic performance was reached in a combination of fecal calprotectin (fCal) and EDN i.e., 88.9% and 84%, respectively. Fecal EDN and fCAl are reliable tools in differentiating between food protein-induced allergic proctocolitis and gastrointestinal functional disorders in infants. Full article

This is the first study to assess confocal laser endomicroscopy (CLE) use within the transsphenoidal approach and show the feasibility of obtaining digital diagnostic biopsies of pituitary tumor tissue after intravenous fluorescein injection. We confirmed that the CLE probe reaches the tuberculum sellae through the transnasal transsphenoidal corridor in cadaveric heads. Next, we confirmed that CLE provides images with identifiable histological features of pituitary adenoma. Biopsies from nine patients who underwent pituitary adenoma surgery were imaged ex vivo at various times after fluorescein injection and were assessed by a blinded board-certified neuropathologist. With frozen sections used as the standard, pituitary adenoma was diagnosed as “definitively” for 13 and as “favoring” in 3 of 16 specimens. CLE digital biopsies were diagnostic for pituitary adenoma in 10 of 16 specimens. The reasons for nondiagnostic CLE images were biopsy acquisition <1 min or >10 min after fluorescein injection (n = 5) and blood artifacts (n = 1). In conclusion, fluorescein provided sufficient contrast for CLE at a dose of 2 mg/kg, optimally 1–10 min after injection. These results provide a basis for further in vivo studies using CLE in transsphenoidal surgery. Full article

Congestive heart failure (CHF) is the second most prevalent cause of death in rheumatoid arthritis (RA). The systemic inflammatory state in RA patients is deemed responsible for this finding. Anti-inflammatory treatment with anti-tumor necrosis factor (anti-TNF) therapy decreases CV risk and subsequently might improve the cardiac function by lowering the overall inflammatory state. This study investigated the effect of anti-TNF on the cardiac function in RA patients. Fifty one RA patients were included, of which thirty three completed follow-up. Included patients were >18 years, had moderate–high disease activity and no history of cardiac disease. Patients were assessed at baseline and after six months of anti-TNF treatment. Patients underwent conventional Speckle tracking and tissue Doppler echocardiography in combination with clinical and laboratory assessments at baseline and follow-up. The left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) showed no changes during follow-up, LVEF 63% (±9) to 62% (±8) p = 0.097 and GLS −20 (±4) to −20 (±3) p = 0.79, respectively. Furthermore, E/e’ nor E/A changed significantly between baseline and follow-up, respectively 8 (7–9) and 8 (7–9) p = 0.17 and 1.1 (±0.4) and 1.1 (±0.4) p = 0.94. Follow-up NT-proBNP decreased with 23%, from 89 ng/L (47–142) to 69 ng/L (42–155), p = 0.10. Regression analysis revealed no association between change in inflammatory variables and cardiac function. Echocardiography showed no effect of anti-TNF treatment on the cardiac function in RA patients with low prevalence of cardiac dysfunction. Moreover, NT-proBNP decreased, possibly indicating (subtle) improvement of the cardiac function. Full article

Objective: To evaluate the performance of two subjective refraction measurement algorithms by comparing the refraction values, visual acuity, and the time taken by the algorithms with the standard subjective refraction (SSR). Methods: The SSR and two semi-automated algorithm-based subjective refraction (SR1 and SR2) in-built in the Vision-R 800 phoropter were performed in 68 subjects. In SR1 and SR2, the subject’s responses were recorded in the algorithm which continuously modified the spherical and cylindrical component accordingly. The main difference between SR1 and SR2 is the use of an initial fogging step in SR1. Results: The average difference and agreement limits intervals in the spherical equivalent between each refraction method were smaller than 0.25 D, and 2.00 D, respectively. For the cylindrical components, the average difference was almost zero and the agreement limits interval was less than 0.50 D. The visual acuities were not significantly different among the methods. The times taken for SR1 and SR2 were significantly shorter, and SR2 was on average was three times faster than SSR. Conclusions: The refraction values and the visual acuity obtained with the standard subjective refraction and algorithm-based methods were similar on average. The algorithm-based methods were significantly faster than the standard method. Full article

Increase in left ventricular (LV) mass develops as a compensatory mechanism against pressure overload in aortic valve stenosis. However, long-standing LV geometrical changes are related to poor prognosis. The LV geometrical change occurs after transcatheter aortic valve replacement (TAVR). The present study aimed to investigate the relationship between improvement in valvuloarterial impedance (Zva) and change in LV mass index (LVMI) and the ratio of LVMI to LV end-diastolic volume index (LVMI/LVEDVI). We compared these relationships to that between Zva and mean pressure gradient (MPG). Baseline and follow-up transthoracic echocardiograms of 301 patients who underwent TAVR from November 2011 to December 2015 were reviewed. Spearman correlation coefficient (ρ) was used to compare ΔLVMI and ΔLVMI/LVEDVI with Zva or MPG. The correlation between ΔZva and ΔLVMI (ρ = 0.47, p < 0.001) was superior to that between ΔMPG and ΔLVMI (ρ = 0.15, p = 0.009) (p for comparison < 0.001). The correlation between ΔZva and ΔLVMI/LVEDVI was statistically significant (ρ = 0.54, p < 0.001); in contrast, that of ΔMPG and ΔLVMI/LVEDVI was not. The improvement in Zva after TAVR was more closely related to LVMI and LVMI/LVEDVI reduction than MPG reduction. Full article