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Purpose-Prognosis of Duchenne muscular dystrophy (DMD) is related to cardiac dysfunction. Two dimensional-speckle tracking echocardiography (2D-STE) has recently emerged as a non-invasive functional biomarker for early detection of DMD-related cardiomyopathy. This study aimed to determine, in DMD children, the existence of a left ventricle (LV) dyssynchrony using 2D-STE analysis.Methods-This prospective controlled study enrolled 25 boys with DMD (mean age 11.0±3.5 years) with normal LV ejection fraction and 50 age-matched controls. Three measures were performed to assess LV mechanical dyssynchrony: the opposing-wall delays (longitudinal and radial analyses), the modified Yu index, and the time-to-peak delays of each segment. Feasibility and reproducibility of 2D-STE dyssynchrony were evaluated. Results-All three mechanical dyssynchrony criteria were significantly higher in the DMD group than in healthy subjects: (1) opposing-wall delays in basal inferoseptal to basal anterolateral segments (61.4±45.3 msec vs. 18.3±50.4 msec, Prespectively) and in mid inferoseptal to mid anterolateral segments (58.6±35.3 msec vs. 42.4±36.4 msec, Prespectively), (2) modified Yu index (33.3±10.1 msec vs. 28.5±8.1 msec, P, respectively), and (3) most of time-to-peak values, especially in basal and mid anterolateral segments. Feasibility was excellent and reliability was moderate to excellent, with ICC values ranging from 0.49 to 0.97.Conclusion-Detection of LV mechanical dyssynchrony using 2D-STE analysis is an easily and reproducible method in pediatrics. The existence of an early LV mechanical dyssynchrony visualized using 2D-STE analysis in children with DMD before the onset of cardiomyopathy represents a perspective for future pediatric drug trials in the DMD-related cardiomyopathy prevention. Clinical Trial Registration-Clinicaltrials.gov NCT02418338. Post-hoc study, registered on April 16, 2015.

Human papillomavirus genotypes (HPVs) have been confirmed to be the major cause of cervical intraepithelial neoplasia (CIN) that remains to be one of the most common women cancers around the world. It seems other risk factors have synergistic effects on cervical cancer occurrence including smoking, dietary pattern, sexual behavior, ethnicity, epigenetics, and environmental hazardous materials. Our study characterized the potential cancerous role of lead (Pb) as a common toxic environmental pollutant agent on CIN outcomes. Lead concentration was quantified using an atomic absorption spectrometer in liquid-based cytology specimens of 40 CIN-HPV positive subjects, 50 HPV infected non-cancerous cases, and 43 non-HPV infected/non-cancerous women. Pb concentration was 5.5 (4.7–6.4) μg/dL, 4.7 (4.2–8.7) μg/dL, and 4.7 (4.5–5.4) μg/dL in the CIN-HPV positive group, HPV infected non-cancerous cases, and non-HPV infected/non-cancerous group, respectively. The results showed higher Pb concentration is associated with higher risk for cervical malignancy in comparison with non-HPV infected/non-cancerous subjects, after controlling for age effect (aOR = 4.55, 95% CI: 1.55–15.07, P < 0.01). Our finding suggested a direct significant association between Pb accumulation and CIN existence. The consequences need to be further validated by including more relevant risk factors and controlling the confounders for better understating of Pb impact from outdoor air pollution on cervical cancer progression.

Leptospirosis is an emerging infectious disease caused by pathogenic Leptospira spp. A universal vaccine against leptospirosis is likely to require highly conserved epitopes from pathogenic leptospires that are exposed on the bacterial surface and that generate a protective and sterilizing immune response. Our group recently identified several genes predicted to encode TonB-dependent receptors (TBDR) in Leptospira interrogans using a reverse vaccinology approach. Three leptospiral TBDRs were previously described and partially characterized as ferric-citrate, hemin, and cobalamin transporters. In the current study, we designed a fusion protein composed of predicted surface-exposed epitopes from three conserved leptospiral TBDRs. Based on their three-dimensional structural models and the prediction of immunogenic regions, nine putative surface-exposed fragments were selected to compose a recombinant chimeric protein. A Mycobacterium bovis BCG strain expressing this chimeric antigen encoded in the pUP500/PpAN mycobacterial expression vector was used to immunize Syrian hamsters. All animals (20/20) vaccinated with recombinant BCG survived infection with an endpoint dose of L. interrogans (p

Hypoxia in the tumor microenvironment (TME) greatly limits the tumor-killing therapeutic efficacy of sonodynamic therapy (SDT); this phenomenon is further exacerbated by increased glutathione (GSH) levels in cancer cells. Simultaneously, cancer starvation therapy is increasingly recognized nowadays as a promising clinical translation but the efficacy of glucose oxidase (GOx)-based starvation therapy is also limited by the lack of oxygen in the tumor. Glucuronide 3-phosphate dehydrogenase (GADPH) is a key glycolytic enzyme and can therefore be a target for starvation therapy in the absence of oxygen engagement. Here, we innovatively proposed thiol–ene click reactions based on a two-dimensional metal–organic framework (MOF) modification for tumor treatments to enable the combination of SDT and starvation therapy. Experimental studies demonstrated that the prepared material could consume GSH and GADPH free from oxygen in TME, which benefited from the thiol–ene click reactions between the MOF and thiol substances in cancer cells. Further experiments in vitro and in vivo indicated the prepared MOF materials could kill cancer cells efficiently. This study is expected to create a promising avenue for thiol–ene click reactions in SDT therapy and cancer starvation therapy for cancer.

Objective To assess prevalence of CT imaging-derived sarcopenia, osteoporosis, and visceral obesity in clinically frail and prefrail patients and determine their association with the diagnosis of frailty. Materials and methods This cross-sectional study was constructed using our institution’s pelvic trauma registry and ambulatory database registry. The study included all elderly pelvic trauma patients and ambulatory outpatients between May 2016 and March 2020 who had a comprehensive geriatric assessment and CT abdomen/pelvis within 1 year from the date of the assessment. Patients were dichotomized in prefrail or frail groups. The study excluded patients with history of metastatic disease or malignancy requiring chemotherapy. Results The study cohort consisted of 151 elderly female and 65 male patients. Each gender population was subdivided into frail (114 female [75%], 51 male [78%]) and prefrail (37 female [25%], 14 male [22%]) patients. CT-imaging-derived diagnosis of osteoporosis (odds ratio, 2.5; 95% CI: 1.2–5.5) and sarcopenia (odds ratio, 2.6; 95% CI: 1.2–5.6) were associated with frailty in females, but did not reach statistical significance in males. BMI and subcutaneous adipose tissue at L3 level were statistically lower in the frail male group compared to the prefrail group. BMI showed strong correlation with the subcutaneous area at the L3 level in both genders (Spearman’s coefficient of 0.8, p

Purpose International uniformity of definition and classification are crucial for diagnosis and management of cauda equina syndrome (CES). They are also useful for clinicians when discussing CES with patients and relatives, and for medicolegal purposes. Methods We reviewed published literature using PubMed on definition and classification of cauda equina syndrome since 2000 (21 years). Using the search terms ‘cauda equina’ and ‘definition’ or ‘classification’, we found and reviewed 212 papers. Results There were 17 different definitions of CES used in the literature. There were three well-defined methods of classification of CES. The two-stage system of incomplete CES (CESI) versus CES with retention (CESR) is the most commonly used classification, and has prognostic value although the details of this continue to be debated. Conclusion We used the existing literature to propose a clear definition of CES. We also drew on peer-reviewed published literature that has helped to amplify and expand the CESI/CESR dichotomy, adding categories that are both less severe than CESI, and more severe than CESR, and we propose clear definitions in a table form to assist current and future discussion and management of CES.

Purpose This study aims to assess the results, rebubbling rate, and graft survival after Descemet membrane endothelial keratoplasty (DMEK) with regard to the number and type of previous glaucoma surgeries. Methods This is a clinical retrospective review of 1845 consecutive DMEK surgeries between 07/2011 and 08/2017 at the Department of Ophthalmology, University of Cologne. Sixty-six eyes were included: group 1 (eyes with previous glaucoma drainage devices (GDD); n = 27) and group 2 (eyes with previous trabeculectomy (TE); n = 39). Endothelial cell loss (ECL), central corneal thickness, graft failure, rebubbling rate, and best spectacle-corrected visual acuity (BSCVA) up to 3 years after DMEK were compared between subgroups of patients with different numbers of and the two most common types of glaucoma surgeries either GDD or TE or both. Results Re-DMEK rate due to secondary graft failure was 55.6% (15/27) in group 1 and 35.9% in group 2. The mean graft survival time in group 1 was 25 ± 11 months and 31.3 ± 8.6 months in group 2 (p = 0.009). ECL in surviving grafts in group 1 was 35% (n = 13) at 6 months, 36% at 12 months (n = 8), and 27% (n = 4) at 2 years postoperatively. In group 2, ECL in surviving grafts was 41% (n = 10) at 6 months, 36% (n = 9) at 12 months, and 38% (n = 8) at 2 years postoperatively. Rebubbling rate in group 1 was 18.5% (5/27) and 35.9% (14/39) in group 2 (p = 0.079). Conclusion Eyes with previous GDD had no higher risk for an increased rebubbling rate but a higher risk for a re-DMEK due to secondary graft failure with a mean transplant survival time of about 2 years. Compared to eyes with preexisting glaucoma drainage device, eyes after trabeculectomy had less secondary graft failures and a longer mean graft survival rate.

Objective This study was aimed to compare different stenting techniques for coronary bifurcation disease (CBD). Background Percutaneous coronary intervention (PCI) remains controversial for CBD; over the years, several stent techniques for bifurcation lesions have been used. Current guidelines recommend a provisional single-stent strategy as the preferred method for coronary artery bifurcation lesions. However, several randomized controlled trials (RCT) indicated that two-stent techniques showed better clinical outcomes. Methods We systematically searched Embase, PubMed, and Web of Science to include RCTs. The primary endpoint was the major adverse cardiovascular event (MACE). Secondary outcomes were cardiac death, myocardial infarction (MI), target-lesion or target-vessel revascularization (TLR or TVR), and definite or probable stent thrombosis (ST). Finally, we used 26 RCTs and a total of 7257 individuals were randomly assigned to one of the 6 stent techniques and included in this network meta-analysis. Results In our network meta-analysis, double-kissing (DK) crush was significantly more superior to other 5 stent techniques in MACEs: OR vs. provisional 0.40 (95% CI 0.28–0.55); vs. culotte 0.40 (95% CI 0.26–0.60). DK crush ranked the most effective treatment for MACE (100%), MI (75%), ST (83%), and TLR (100%) in the rank probabilities analysis. In patients with complex bifurcation lesion defined by DEFINITION criteria, DK crush was notably more efficacious than provisional, culotte, and T-stenting/T-stenting and protrusion (TAP) in MACEs (OR vs. provisional 0.26, 95% CI 0.13–0.52) and TLR (OR vs. provisional 0.24, 95% CI 0.10–0.58). Conclusion Compared with other stenting techniques, DK crush had a lower incidence of MACEs in CBD. DK crush was significantly associated with a lower rate of MACEs in patients with complex bifurcation lesions defined by the DEFINITION criterion. Graphical abstract

PURPOSE To describe the outcomes of surgical bleb revisions from a tertiary glaucoma service in Singapore. METHODS One hundred and thirty-one eyes of 129 patients who underwent surgical bleb revisions at the Singapore National Eye Centre between 2007 and 2014 were included in the study. The indications for bleb revision were: bleb-related infection (BRI), early and late bleb leak, early and late overfiltration, and bleb dysesthesia. Regression analysis was applied to elucidate risk factors. RESULTS The mean age of the patients was 66 years, 62.6% were male, and 88.5% were Chinese. The majority of the eyes had primary glaucoma (79.4%). The mean interval from the initial trabeculectomy or phaco-trabeculectomy to the bleb revision was 58.8 months. The overall success rate was 69.5%. By Kaplan-Meier survival analysis, the overall cumulative success range fell from 78.6% to 49.1% over 10 years. Eyes with early bleb leak had lower surgical success compared to eyes with late bleb leak, early overfiltration and late overfiltration (P = 0.026, log-rank test). The IOP improved significantly post-operatively for eyes with BRI, early bleb leak, late bleb leak, early overfiltration and overfiltration (P

ZusammenfassungEs gibt bisher wenige beschriebene Fälle von Bissen durch die Hakennasennatter (Heterodon nasicus), die meist zu einer Lokalreaktion führten. Wir berichten über eine ausgeprägte Lokalreaktion nach dem Biss einer als Haustier gehaltenen Hakennasennatter (Heterodon nasicus). Eine antiseptische Lokaltherapie und Antibiose zur Infektionsprophylaxe sind zu empfehlen, ebenfalls Laborkontrollen zum Ausschluss einer systemischen Beteiligung. An die Überprüfung des Tetanusschutzes sollte gedacht werden.

INTRODUCTION Bluman et al., flatfoot classification is based on posterior tibial tendon (PTT) dysfunction leading to a chronological appearance of several foot deformities. An expert consensus recently proposed a new classification named Progressive Collapsing Foot Deformity (PCFD) in which the focus was shifted to five different independent foot and ankle deformities and their flexibility or rigidity. The aim of this study was to compare Bluman and PCFD classifications. We hypothesize that both classifications will be reliable and that the PCFD classification will allow a larger distribution of the different types of foot deformity. MATERIALS AND METHODS We performed a retrospective IRB-approved study including 92 flatfeet. Three foot and ankle surgeons reviewed patient files and radiographs to classify each foot using both classifications. Bluman classification was performed one time as initially described and a second time after removing the Angle of Gissane sclerosis sign. Interobserver reliabilities were determined with Fleiss' kappa values. RESULTS Interobserver reliabilities of Bluman and PCFD classifications were, respectively, substantial 0.67 and moderate 0.55. PCFD Class C and D reliabilities were, respectively, slight 0.07 and fair 0.28. The 276 readings were spread into 10 substages in Bluman and 65 subclasses in PCFD. The progressivity of the Bluman classification prevented the combination of flexible hindfoot valgus (II Bluman, 1A PCFD), midfoot abduction (IIB, 1B) and medial column instability (IIC, 1C) which was frequent in our study (112/276 readings, 40.6%). By removing the Angle of Gissane sclerosis sign from the Bluman classification, the prevalence of stage III decreased from 44.2 to 10.1%. CONCLUSIONS Bluman and PCFD classifications were reliable. The PCFD classification showed a larger distribution of different types of flatfeet but Classes C and D need better definition. The progressivity of Bluman classification causes inconsistencies and Gissane angle sclerosis sign is inappropriately used and might lead to incorrect surgical indications.

Using a 50-kV INTRABEAM® system after breast-conserving surgery, breast skin injury and long treatment time remain the challenging problems when large-size spherical applicators are used. This study has aimed to address these problems using gold (Au) nanoparticles (NPs). For this, surface and isotropic doses were measured using a Gafchromic EBT3 film and a water phantom. The particle propagation code EGSnrc/Epp was used to score the corresponding doses using a geometry similar to that used in the measurements. The simulation was validated using a gamma index of 2%/2 mm acceptance criterion in the gamma analysis. After validation Au-NP-enriched breast tissue was simulated to quantify any breast skin dose reduction and shortening of treatment time. It turned out that the gamma value deduced for validation of the simulation was in an acceptable range (i.e., less than one). For 20 mg-Au/g-breast tissue, the calculated Dose Enhancement Ratio (DER) of the breast skin was 0.412 and 0.414 using applicators with diameters of 1.5 cm and 5 cm, respectively. The corresponding treatment times were shortened by 72.22% and 72.30% at 20 mg-Au/g-breast tissue concentration, respectively. It is concluded that Au-NP-enriched breast tissue shows significant advantages, such as reducing the radiation dose received by the breast skin as well as shortening the treatment time. Additionally, the DERs were not significantly dependent on the size of the applicators.

While exercise and physical activity have been suggested to reduce mortality and symptoms in cancer, knowledge on these associations in patients with childhood cancer (CCPs) is sparse. Anti-inflammatory properties of exercise might mediate these beneficial effects. We investigated the influence of exercise on the inflammation markers neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and systemic-immune-inflammation index (SII) and associations to patient-reported-outcomes in CCPs in a randomized-controlled trial. Results show associations between inflammation markers and patient-reported outcomes. Compared to the control group, SII was significantly reduced following exercise (p=0.036). Anti-inflammatory effects of exercise are also present in CCPs and may underlie exercise-induced benefits on symptoms. Clinical Trial Registration Number: NCT02612025, Supportive care in cancer;Bd 30. 2021, Heft 4, S. 2905-2908

BACKGROUND By identifying diseases of the anterior segment of the eye associated with exposure to UV light, recommendations for action can be derived. AIM After reading this review, the reader should be familiar with UV light-associated diseases of the anterior segment of the eye. METHOD Using a selective literature search, UV light-associated diseases of the anterior segment of the eye were identified and protective mechanisms are described. RESULTS The UV light-associated lesions of the anterior segment of the eye include basal cell and squamous cell carcinomas, malignant melanoma of the eyelids and conjunctiva, pterygium, keratoconjunctivitis photoelectrica and climatic droplet keratopathy as well as cortical cataract. CONCLUSION Eyeglasses for filtering UV light, sunglasses and special safety glasses, such as welding helmets and wearing headgear protect against UV light exposure to the anterior segment of the eye and the associated diseases.

Objectives This study investigated the 10-year trends of weight and prevalence of underweight, overweight and obesity according to disability grade and types compared with those without disabilities. Methods This serial cross-sectional analysis was conducted using national disability registration data with national general health checkup data from 2008 to 2017. Age-standardized prevalence of underweight and obesity were analyzed for each year, according to the presence, type, and severity of disabilities. Odds of underweight, overweight, obesity, and severe obesity were examined by multinomial logistic regression after adjusting for socio-demographic and clinical variables using data in 2017. Results Over 10 million subjects in each year were included in the analysis. In 2017, 14,246,785 people with age between 19 and 110 years were included and 53.1% was men. For 10 years, age-standardized prevalence of obesity and severe obesity showed significant increases regardless of sex and presence of disability. However, age-standardized underweight prevalence in people without disability tended to decrease whereas it was an increase in 2012 and the prevalence has remained steady since in people with disability. People with disabilities had higher odds of underweight compared to those without disability (OR 1.41, 95% CI 1.38–1.44 in male and OR 1.31, 95% CI 1.28–1.34 in female), especially in those with severe disabilities (OR 2.00, 95% CI 1.94–2.06 in male and OR 1.83, 95% CI 1.77–1.89 in female). Women with disabilities are more likely to be obese than those without disabilities regardless of disability severity (OR 1.40, 95% CI 1.38–1.41). Participants with mental disorder showed the highest prevalence of obesity, followed by epilepsy and developmental disability. Conclusions Having a disability was associated with higher odds/probability of both obesity and underweight. The intersection of female, severe disability, and mental/developmental disabilities was associated with probability of severe obesity. Simultaneous efforts are needed to develop health policy to reduce both the prevalence of obesity and underweight.

Cenani-Lenz syndrome (CLS) is a rare autosomal-recessive congenital disorder affecting development of distal limbs. It is characterized mainly by syndactyly and/or oligodactyly, renal anomalies, and characteristic facial features. Mutations in the LRP4 gene, located on human chromosome 11p11.2-q13.1, causes the CLS. The gene LRP4 encodes a low-density lipoprotein receptor-related protein-4, which mediates SOST-dependent inhibition of bone formation and Wnt signaling. In the study, presented here, three families of Pakistani origin, segregating CLS in the autosomal recessive manner were clinically and genetically characterized. In two families (A and B), microsatellite-based homozygosity mapping followed by Sanger sequencing identified a novel homozygous missense variant [NM_002334.3: c.295G>C; p.(Asp99His)] in the LRP4 gene. In the third family C, exome sequencing revealed a second novel homozygous missense variant [NM_002334.3: c.1633C>T; p.(Arg545Trp)] in the same gene. To determine the functional relevance of these variants, we tested their ability to inhibit canonical WNT signaling in a luciferase assay. Wild type LRP4 was able to inhibit LRP6-dependent WNT signaling robustly. The two mutants p.(Asp99His) and p.(Arg545Trp) inhibited WNT signaling less effectively, suggesting they reduced LRP4 function.

Purpose Metastatic oesophageal cancer is commonly considered as a palliative situation with a poor prognosis. However, there is increasing evidence that well-selected patients with a limited number of liver metastases (ECLM) may benefit from a multimodal approach including surgery. Methods A systematic review of the current literature for randomized trials, retrospective studies, and case series with patients undergoing hepatectomies for oesophageal and oesophagogastric junction cancer liver metastases was conducted up to the 31st of August 2021 using the MEDLINE (PubMed) and Cochrane Library databases. Results A total of 661 articles were identified. After removal of duplicates, 483 articles were screened, of which 11 met the inclusion criteria. The available literature suggests that ECLM resection in patients with liver oligometastatic disease may lead to improved survival and even long-term survival in some cases. The response to concomitant chemotherapy and liver resection seems to be of significance. Furthermore, a long disease-free interval in metachronous disease, low number of liver metastases, young age, and good overall performance status have been described as potential predictive markers of outcome for the resection of liver metastases. Conclusion Surgery may be offered to carefully selected patients to potentially improve survival rates compared to palliative treatment approaches. Studies with standardized patient selection criteria and treatment protocols are required to further define the role for surgery in ECLM. In this context, particular consideration should be given to neoadjuvant treatment concepts including immunotherapies in stage IVB oesophageal and oesophagogastric junction cancer.

Summary Background The relationship between acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) and levels of certain inflammatory factors remains controversial. The purpose of this meta-analysis was to summarize the available studies evaluating the association between levels of inflammatory factors and ARDS/ALI incidence. Methods We searched the PubMed, EmBase, and Cochrane databases for studies published up to July 2017. For each inflammatory factor, a random effects model was employed to pool results from different studies. Results We identified 63 studies that included 6243 patients in our meta-analysis. Overall, the results indicated that the levels of angiopoietin (ANG)-2 (standard mean difference, SMD: 1.34; P P = 0.012), IL‑6 (SMD: 0.66; P = 0.005), and tumor necrosis factor (TNF)-α (SMD: 0.98; P = 0.001) were significantly higher in patients with ARDS/ALI than in unaffected individuals. No significant differences were observed between patients with ARDS/ALI and unaffected individuals in terms of the levels of IL‑8 (SMD: 0.61; P = 0.159), IL-10 (SMD: 1.10; P = 0.231), and plasminogen activator inhibitor (PAI)-1 (SMD: 0.70; P = 0.060). Conclusions ARDS/ALI is associated with a significantly elevated levels of ANG‑2, IL-1β, IL‑6, and TNF‑α, but not with IL‑8, IL-10, and PAI‑1 levels.

BACKGROUND The rarity of esophageal achalasia has resulted in little being known about the characteristics of its three subtypes. The upper esophageal sphincter is considered one key factor to prevent aspiration pneumonia, a serious complication of esophageal achalasia. This study aimed to reveal the subtype characteristics of esophageal achalasia and how the upper esophageal sphincter functions and relates to other clinical parameters of the disease. METHODS We retrospectively investigated the clinical records of patients diagnosed with esophageal achalasia. All participants underwent esophagogastroduodenoscopy and then, within 2 weeks, high-resolution manometry. Gastrointestinal symptoms were assessed using a previously validated self-reported questionnaire. RESULTS A total of 110 patients with esophageal achalasia were enrolled: 50 with type I, 40 with type II, and 20 with type III. Mean age at diagnosis was 54.5, 50.4, and 66.1 years for types I, II, and III, respectively. Mean resting upper esophageal sphincter pressure was 28.0, 51.8, and 43.6 mmHg for patients with types I, II, and III, respectively (p

PURPOSE In adolescent idiopathic scoliosis (AIS), the rib prominence is a major cosmetic concern which can be improved using thoracoplasties. We sought to determine if the use of deep drains helps minimize the development of pleural effusions after thoracoplasties. METHODS Retrospective study of 45 patients with AIS undergoing posterior spinal fusion (PSF) and thoracoplasties. RESULTS Thirty six out of 45 patients (80.0%) required placement of a deep surgical drain, and 16 out of 45 (35.6%) developed pleural effusions after PSF with concomitant thoracoplasty. Of the 16 patients who developed pleural effusion, 12 of 36 (33.3%) required a placement of a deep drain (p > 0.05). Of the total 45 patients in this cohort, 3 patients (6.7%) required chest tubes, and 4 patients (8.9%) developed surgical site infections (SSIs). We found that deep drains were associated with a lower incidence of SSI (2.8% vs 33.3%; p = 0.021). Patients who had a pleural effusion had longer ICU stays (p = 0.037) and longer requirements of nasal oxygen (p = 0.025). DISCUSSION The presence of a pleural effusion in patients with AIS undergoing PSF with thoracoplasty was associated with longer oxygen requirements and length of hospital ICU admission. Thirty six percent of patients with thoracoplasties developed pleural effusions, but deep subfascial drains did not significantly decrease the incidence of pleural effusions.

Intrauterine infections are an urgent problem of modern neonatology. One of the causes of intrauterine infective foetal lesions is physiological immunosuppression. The purpose of this study is to investigate the cytokine status in newborns infected with perinatal infections, depending on their body weight. The study examined 145 newborns. Taking into account their body weight, they were divided into 2 groups: main and secondary. The study was conducted in the immunological laboratory of the Medical Centre of Marat Ospanov West Kazakhstan Medical University in the city of Aktobe, with the determination of the level of IgM and IgG to the herpes simplex virus (HSV) types 1, 2, cytomegalovirus (CMV), and chlamydia using the MULTISKANASCENT analyser with the "Chemo" T system. The main results of this study are the predominance of the anti-inflammatory component in both normal weight and underweight infants, which is evidence of the Th-cell-mediated immune response prevalence. The applied value of this study lies in the possibility of applying its results in practice to obtain effective methods to counteract the occurrence and development of intrauterine infections.

A Hotline® fluid warmer is a device commonly used by anesthesia providers in the operating room to warm and infuse blood products and large fluid volumes. The purpose of the fluid warmer is to counter heat loss, which occurs under anesthesia. Despite normal checks performed prior to its use, we discovered a breach in the fluid warming set attached to the Hotline® fluid warmer during blood administration. The breach contaminated the patient's sterile intravenous line. We describe the quality and safety processes we undertook in detail. We discuss the notion that monitoring alarms are an important safety feature of most modern devices utilized by anesthesia providers. We believe the Hotline® fluid warmer lacks a crucial monitor for detecting a breach within the fluid warming set, and therefore recommend the addition of an alarm to improve this device's safety.

OBJECTIVE The purpose of this paper was to examine changes in situational temptations to smoke among women in early to late pregnancy enrolled in a texting trial to help them quit smoking. We compared changes between (1) intervention arms, (2) those who quit, (3) those who reduced by 50% or more, and (4) those who reduced by less than 50%. We also examined cravings overtime in the intervention arm and the relationship between real-time cravings assessed via text message and situational temptations. METHODS This was a secondary analysis of the Baby Steps trial, a randomized controlled trial testing the efficacy of a text-based scheduled gradual reduction (SGR) intervention on cessation. We used t-tests to examine changes across intervention arms and repeated measured proc mixed to explore changes in situational temptations and cravings. RESULTS Among all women, situational temptations decreased from early to late pregnancy for the positive, negative, and habitual subscales, (ps

Purpose Major disadvantages of the percutaneous coronary intervention (PCI) are the high occurrence of repeat revascularization due to restenosis and disease progression. The current study aimed to identify indicators that can predict the risk of repeat revascularization. Methods A total of 143 patients who underwent PCI and had genetic test results were enrolled. We retrospectively reviewed their medical records after the first PCI. P2Y12 reaction units (PRU) test results were obtained by VerifyNow; 372 SNPs of NOS3, MMP3, AGT, and AGT1R gene and 380 genes related to platelet activation-related processes and clopidogrel activity were selected for analysis. Repeat revascularization and in-stent restenosis (ISR) were used as clinical outcomes, and PRU and ADP aggregation rates were used as platelet function outcomes in analysis. Results After the first PCI, the incidence of repeat revascularization at 18, 30, and 42 months was 14.1% (20/142), 17.5% (24/137), and 39.7% (31/78), respectively. In the candidate gene analysis, Rs 78830 (NOS3) was associated with both ADP aggregation rate and 18- and 30-month ISR, and rs 62275847 (AGTR1) was associated with both ADP aggregation rate and 30-month ISR. In the pathway, gene-set analysis, the linkage rs471683 and rs7785386 of GNAI1|GNAT3 were associated with PRU and ADP aggregation rate, 18-months and 30-months ISR, and repeat revascularization within 30 months. Rs1715389 of GNAI1|GNAT3 were associated with both PRU and ADP aggregation rate, 18-months and 30-months ISR, and repeat revascularization within 30 months. Rs7313458 of ITPR2 were associated with PRU and ADP aggregation rate, 18-months and 30-months ISR, and repeat revascularization within 18 months. Conclusions The genetic polymorphisms of rs78830(NOS3), rs62275874 (AGTR1), linkage rs471683 and rs7785386 (GNAI1|GNAT3), rs1715389(GNAI1|GNAT3), and rs7313458 (ITPR2) may lead to an increased risk of in-stent restenosis and revascularization after the first PCI in Chinese patients by affecting the efficacy of clopidogrel. The above six SNP may be used as potential genetic biomarkers for high risk of in-stent restenosis and revascularization after the first PCI in Chinese patients.

With more than 5500 da Vinci Surgical System (DVSS) installed worldwide, the robotic approach for general surgery, including for inguinal hernia repair, is gaining popularity in the USA. However, in many countries outside the USA, robotic surgery is performed at only a few advanced institutions; therefore, its advantages over the open or laparoscopic approaches for inguinal hernia repair are unclear. Several retrospective studies have demonstrated the safety and feasibility of robotic inguinal hernia repair, but there is still no firm evidence to support the superiority of robotic surgery for this procedure or its long-term clinical outcomes. Robotic surgery has the potential to overcome the disadvantages of conventional laparoscopic surgery through appropriate utilization of technological advantages, such as wristed instruments, tremor filtering, and high-resolution 3D images. The potential benefits of robotic inguinal hernia repair are lower rates of complications or recurrence than open and laparoscopic surgery, with less postoperative pain, and a rapid learning curve for surgeons. In this review, we summarize the current status and future prospects of robotic inguinal hernia repair and discuss the issues associated with this procedure.

Angina is a significant contributor to disability and impairment in quality of life in patients with chronic coronary syndromes (CCS). An elevated heart rate (HR) may trigger myocardial ischemia by increasing oxygen consumption and decreasing the diastolic time, compromising the coronary flow. HR-lowering strategies offer symptom control and prevent cardiovascular events in subgroups of patients with CCS. However, the best therapeutic approach to achieve the desired HR in patients with CCS can be challenging based on efficacy and tolerability. Guidelines usually propose β-blockers and/or non-dihydropyridine calcium channel blockers (CCB) for angina patients with elevated HR. Nonetheless, there is no clear evidence of greater antianginal efficacy of this strategy versus an alternative HR-lowering agent. Ivabradine reduces the HR by blocking the If current in the sinoatrial node without affecting myocardial contractility or vascular tone. The magnitude of the HR reduction by ivabradine is proportional to the initial HR, which decreases the risk of significant bradycardia. Ivabradine increases the diastolic time and the coronary flow reserve to a greater extent than β-blockers and favors collateralization, improving the regional blood flow. We present two clinical cases of patients with symptomatic CCS in whom HR control with ivabradine was fundamental for symptom control and improvement in left ventricular (LV) function. An earlier combination of ivabradine plus β-blockers would have provided more rapid symptom control and improved LV function in the first case. In the second case, the primary mechanism responsible for angina was most likely a coronary vasomotor abnormality, in which the use of β-blockers aggravated the discomfort. The combination of a dihydropyridine CCB plus ivabradine was highly influential in symptom control. Due to its effects beyond HR reduction and good tolerability, ivabradine should be considered an essential ally in managing patients with angina and high HR with or without LV dysfunction.

In many types of cancer, tumor cells prefer to use glycolysis as a major energy acquisition method. Here, we found that the 18fluoro-deoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT)-based markers were positively associated with the expression of programmed cell death ligand 1 (PD-L1), pyruvate kinase M2 (PKM2), both of which indicate poor prognosis in patients with pancreatic ductal adenocarcinoma (PDAC). However, the regulatory mechanism of PD-L1 remains elusive. In this study, we confirmed that transforming growth factor-beta1 (TGF-β1) secreted by tumor-associated macrophages (TAMs) was a key factor contributing to the expression of PD-L1 in PDAC cells by inducing the nuclear translocation of PKM2. Using co-immunoprecipitation and chromatin immunoprecipitation assays, we demonstrated that the interaction between PKM2 and signal transducer and activator of transcription 1 (STAT1) was enhanced by TGF-β1 stimulation, which facilitated the transactivation of PD-L1 by the binding of PKM2 and STAT1 to its promoter. In vivo, PKM2 knockdown decreased PD-L1 expression in PDAC cells and inhibited tumor growth partly by promoting natural killer cell activation and function, and the combination of PD-1/PD-L1 blockade with PKM2 knockdown limited tumor growth. In conclusion, PKM2 significantly contributes to TAM-induced PD-L1 overexpression and immunosuppression, providing a novel target for immunotherapies for PDAC.

The VRAG-R is a well-established actuarial risk-assessment instrument, which was originally developed for assessing violent recidivism risk in adult male offenders. Whether or not the VRAG-R can also predict violent recidivism in young offenders is unclear so far. In the emergence of juvenile offending, attention-deficit/hyperactivity disorder (ADHD) seems to be of major importance suggesting that it could be relevant for risk assessment as well. Thus, we examined the predictive accuracy of the VRAG-R in a high-risk sample of N = 106 (M = 18.3 years, SD = 1.8) young offenders and assessed the incremental predictive validity of ADHD symptomatology beyond the VRAG-R. Within a mean follow-up time of M = 13 years (SD = 1.2), n = 65 (62.5%) young offenders recidivated with a violent offense. We found large effect sizes for the prediction of violent and general recidivism and re-incarcerations using the VRAG-R sum scores. Current ADHD symptomatology added incremental predictive validity beyond the VRAG-R sum scores concerning the prediction of general recidivism but not of violent recidivism. The results supported the use of the VRAG-R for predicting violent recidivism in young offenders. Because ADHD symptomatology improves the predictive performance of the VRAG-R regarding general recidivism, we argue that addressing ADHD symptoms more intensively in the juvenile justice system is of particular importance concerning a successful long-term risk management in adolescents and young adults.

EBV-associated gastric cancer accounts for about 10% of all gastric carcinomas worldwide. We aimed to verify the prevalence of EBV in gastric adenocarcinoma samples using FISH and qPCR and comparing the results obtained by both techniques. Gastric cancer samples from 191 cases were analyzed. The FISH assay was performed to detect small EBV RNAs (EBER1) and qPCR was performed to detect the EBV-EBNA-1 gene region. Cohen’s kappa index and the chi-square test were used to compare the methodologies and investigate correlations with the clinical-pathological data of the gastric adenocarcinoma patients. Most of the patients were men, and the average age was 60 years. The intestinal subtype cancer presented more aggressive stages with 90% of patients having a reactive FISH for EBV (EBV+), although the virus infection frequency in epithelial gastric tissue was only 1%. No positive association with clinicopathological features and EBV+ was found by FISH. Using qPCR analysis, the percentage of positive samples was lower (52.4%), and a positive association was found in samples from older patients (> 60 years). Interestingly, 71 qPCR-negative cases were detected by FISH in the presence of non-epithelial cells and in 10 qPCR-positive cases with no evidence of EBV according to FISH. The concordance between the two techniques was low, with only 57.6%. FISH is more informative for associating the gastric carcinoma with EBV positivity in tumor/epithelial cells; however, qPCR can provide relevant information regarding the progression and characteristics of neoplasia.

Achromatopsia (ACHM), also known as rod monochromatism or total color blindness, is an autosomal recessively inherited retinal disorder that affects the cones of the retina, the type of photoreceptors responsible for high-acuity daylight vision. ACHM is caused by pathogenic variants in one of six cone photoreceptor-expressed genes. These mutations result in a functional loss and a slow progressive degeneration of cone photoreceptors. The loss of cone photoreceptor function manifests at birth or early in childhood and results in decreased visual acuity, lack of color discrimination, abnormal intolerance to light (photophobia), and rapid involuntary eye movement (nystagmus). Up to 90% of patients with ACHM carry mutations in CNGA3 or CNGB3, which are the genes encoding the alpha and beta subunits of the cone cyclic nucleotide-gated (CNG) channel, respectively. No authorized therapy for ACHM exists, but research activities have intensified over the past decade and have led to several preclinical gene therapy studies that have shown functional and morphological improvements in animal models of ACHM. These encouraging preclinical data helped advance multiple gene therapy programs for CNGA3- and CNGB3-linked ACHM into the clinical phase. Here, we provide an overview of the genetic and molecular basis of ACHM, summarize the gene therapy-related research activities, and provide an outlook for their clinical application.

Expression of inhibitory designer receptors exclusively activated by designer drugs (DREADDs) on excitatory hippocampal neurons in the hippocampus represents a potential new therapeutic strategy for drug-resistant epilepsy. To overcome the limitations of the commonly used DREADD agonist clozapine, we investigated the efficacy of the novel DREADD ligand JHU37160 in chemogenetic seizure suppression in the intrahippocampal kainic acid (IHKA) mouse model for temporal lobe epilepsy (TLE). In addition, seizure-suppressing effects of chemogenetics were compared to the commonly used anti-epileptic drug (AED), levetiracetam (LEV). Therefore, an adeno-associated viral vector was injected in the sclerotic hippocampus of IHKA mice to induce expression of a tagged inhibitory DREADD hM4Di or only a tag (control) specifically in excitatory neurons using the CamKIIα promoter. Subsequently, animals were treated with LEV (800 mg/kg), clozapine (0.1 mg/kg), and DREADD ligand JHU37160 (0.1 mg/kg) and the effect on spontaneous seizures was investigated. Clozapine and JHU37160-mediated chemogenetic treatment both suppressed seizures in DREADD-expressing IHKA mice. Clozapine treatment suppressed seizures up to 34 h after treatment, and JHU37160 effects lasted for 26 h after injection. Moreover, both compounds reduced the length of seizures that did occur after treatment up to 28 h and 18 h after clozapine and JHU37160, respectively. No seizure-suppressing effects were found in control animals using these ligands. Chemogenetic seizure treatment suppressed seizures during the first 30 min after injection, and seizures remained suppressed during 8 h following treatment. Chemogenetics thus outperformed effects of levetiracetam (p

INTRODUCTION The ObserVational survey of the Epidemiology, tReatment, and Care Of MigrainE study in Japan (OVERCOME [Japan]) assessed the impact and burden of migraine in Japan. METHODS OVERCOME (Japan) was a cross-sectional, observational, population-based web survey of Japanese people with migraine conducted between July and September 2020. The burden and impact of migraine were assessed using the Migraine Disability Assessment (MIDAS), Migraine-Specific Quality-of-Life Questionnaire (MSQ), Migraine Interictal Burden Scale (MIBS-4), and Work Productivity and Activity Impairment-Migraine scale. Results were stratified by average number of monthly headache days (0-3, 4-7, 8-14, ≥ 15). RESULTS In total, 17,071 Japanese people with migraine completed the survey. Of these, 14,033 (82.2%) met International Classification of Headache Disorders, 3rd edition criteria for migraine and 9667 (56.6%) reported a physician diagnosis of migraine. Overall, 20.7% of respondents experienced moderate-to-severe disability (MIDAS). Moderate-to-severe interictal burden (MIBS-4) was experienced by 41.5% of respondents. MSQ scores in all domains were lowest in respondents with the most frequent headaches (≥ 15 monthly headache days) and highest in those with the lowest frequency headaches (≤ 3 monthly headache days), indicating poorer quality of life in those with more frequent headaches. Work time missed due to migraine (absenteeism) increased with increasing headache frequency, from 3.8 to 6.2%; presenteeism affected 29.8-49.9% of work time. Although migraine burden was greatest in people with the most frequent headaches, those with the lowest headache frequency still experienced substantial disability, interictal burden, and impacts on productivity and quality of life. There was also substantial unmet need for migraine care: 36.5% of respondents had ever hesitated to seek medical care for their headaches, and 89.8% had never used preventive medication. CONCLUSION In Japan, the burden of migraine and barriers to migraine care are substantial. Improving patient awareness and healthcare provider vigilance may help improve patient outcomes.

ZusammenfassungVorstellung eines 16-jährigen Patienten nach Fahrradsturz beim Mountainbiken 14 Tage nach primärer Versorgung nach offener Epiphysenverletzung. Metaphysär intraossär liegende Steine wurden bei anatomischer Reposition der Fraktur als nebenbefundliches Osteom fehlinterpretiert.

PURPOSE To examine plasma retinol status and its determinants in Chinese pregnant or lactating women. METHODS A cross-sectional study involving 1211 healthy women in mid-pregnancy, late pregnancy, or lactation was conducted in northern, central, and southern China. Plasma retinol concentration was determined by high-performance liquid chromatography. Multivariate quantile regression or modified Poisson regression was used to estimate adjusted medians, or to examine the associations of suboptimal retinol concentration (

Purpose Tumor mutational burden (TMB) is a surrogate biomarker of neo-antigens and high TMB status is associated with favorable response to immune-checkpoint inhibitors (ICIs). This study aimed to elucidate the association between TMB and the outcome of definitive radiotherapy in patients with cervical cancer. Materials and methods TMB and treatment outcome were retrospectively analyzed in patients with newly diagnosed cervical cancer treated with definitive radiotherapy available with somatic mutation data of pre-treatment tumors obtained using a commercially available gene panel. Results The study enrolled 98 patients (median follow-up period, 61 months). The median TMB was 9.5 mutations per megabase (range, 3.0–35.5 mutations per megabase). After dichotomization based on this median value, the 5-year overall survival (OS) for TMB-high patients was significantly worse than that of TMB-low patients (61.1% vs. 82.2%). Multivariate analysis identified high TMB status as a significant prognostic factor for worse OS, along with advanced stage, para-aortic lymph node involvement, and absence of concurrent chemotherapy. Conclusion These data indicate that TMB is a potential prognostic factor for worse survival in patients with cervical cancer treated with definitive radiotherapy, thereby providing a rationale for treatment of TMB-high cervical cancers with a combination of ICIs plus radiotherapy. Secondary abstract This retrospective study of 98 patients demonstrates for the first time that tumor mutational burden (TMB) is an independent prognostic factor for worse overall survival of patients treated with definitive radiotherapy, providing a rationale for treatment of TMB-high cervical cancers with a combination of immune-checkpoint inhibitors plus radiotherapy.

Zusammenfassung Hintergrund Eine adäquate Anpassung der Glukokortikoidsubstitution an unterschiedliche Situationen ist essenziell für Leistungsfähigkeit und Lebensqualität von Patienten mit Nebennierenrindeninsuffizienz (NNRI). Sie dient darüber hinaus der Vermeidung lebensbedrohlicher adrenaler Krisen. Ziel der Arbeit Verbesserung der Versorgung von Patienten mit Nebennierenrindeninsuffizienz. Material und Methoden Selektive Literaturrecherche unter besonderer Berücksichtigung neuerer Studien. Ergebnisse Eine optimale Glukokortikoidsubstitution hat das Ziel, die physiologischen Kortisolschwankungen möglichst genau nachzuahmen. Hier haben in den letzten Jahren Präparate mit veränderter Pharmakokinetik das Therapiespektrum erweitert. Im Vordergrund stehen eine adäquate Anpassung der Substitution in Stresssituationen sowie die Vermeidung und adäquate Behandlung adrenaler Krisen, die mit einer Inzidenz von 4,8 bis 8,3 Krisen pro 100 Patientenjahre auftreten und mit einer Mortalität von etwa 0,5 pro 100 Patientenjahre weiterhin eine tödliche Bedrohung darstellen. Schlussfolgerung Zur Verhinderung lebensbedrohlicher Nebennierenkrisen ist eine Schulung von Patienten, Angehörigen und insbesondere auch medizinischem Personal notwendig.

PURPOSE Growing evidence proved the efficacy of multi-parametric MRI (mpMRI) and prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-guided targeted biopsy (TB) in prostate cancer (PCa) diagnosis, but there is no direct comparison between mpMRI-TB and PSMA PET/CT-TB. Gastrin-releasing peptide receptor (GRPR) is highly expressed in PCa, which can compensate for the unstable expression of PSMA in PCa. Therefore, we designed a study to compare the efficiency of mpMRI-TB, dual-tracer (GRPR and PSMA) PET/CT-TB, systematic biopsy, and combined biopsy for the diagnosis of prostate cancer. METHODS One hundred twelve suspicious PCa patients were enrolled from September 2020 to June 2021. Patients with anyone of positive dual-tracer PET/CT or mpMRI underwent TB, and all enrolled patients underwent systematic biopsy (SB) after TB. The primary outcome was the detection rates of PCa in different biopsy strategies. Secondary outcomes were the performance of three imaging methods, omission diagnostic rates, and upgrading and downgrading of biopsy samples relative to those of prostatectomy specimens in different biopsy strategies. McNemar's tests and Bonferroni correction in multiple comparisons were used to compare the primary and secondary outcomes. RESULTS In 112 men, clinically significant PCa (grade group[GG] ≥ 2) accounted for 34.82% (39/112), and nonclinically significant PCa (GG = 1) accounted for 4.46% (5/112). 68 Ga-PSMA PET/CT-TB achieved higher PCa detection rate (69.77%) and positive ratio of biopsy cores (0.44) compared with SB (39.29% and 0.12) and mpMRI-TB (36.14% and 0.23), respectively (P

Background Cachexia, characterized by involuntary muscle mass loss, negatively impacts survival outcomes, treatment tolerability, and functionality in cancer patients. However, there is a limited appreciation of the true prevalence of low muscle mass due to inconsistent diagnostic methods and limited oncologist awareness. Methods Twenty-nine French healthcare establishments participated in this cross-sectional study, recruiting patients with those metastatic cancers most frequently encountered in routine practice (colon, breast, kidney, lung, prostate). The primary outcome was low skeletal muscle mass prevalence, as diagnosed by estimating the skeletal mass index (SMI) in the middle of the third-lumbar vertebrae (L3) level via computed tomography (CT). Other objectives included an evaluation of nutritional management, physical activity, and toxicities related to ongoing treatment. Results Seven hundred sixty-six patients (49.9% males) were enrolled with a mean age of 65.0 years. Low muscle mass prevalence was 69.1%. Only one-third of patients with low skeletal muscle mass were receiving nutritional counselling and only 28.4% were under nutritional management (oral supplements, enteral or parenteral nutrition). Physicians highly underdiagnosed those patients identified with low skeletal muscle mass, as defined by the primary objective, by 74.3% and 44.9% in obese and non-obese patients, respectively. Multivariate analyses revealed a lower risk of low skeletal muscle mass for females (OR: 0.22, P 0.01) and those without brain metastasis (OR: 0.34, P 0.01). Low skeletal muscle mass patients were more likely to have delayed treatment administration due to toxicity (11.9% versus 6.8%, P = 0.04). Conclusions There is a critical need to raise awareness of low skeletal muscle mass diagnosis among oncologists, and for improvements in nutritional management and physical therapies of cancer patients to curb potential cachexia. This calls for cross-disciplinary collaborations among oncologists, nutritionists, physiotherapists, and radiologists.

Purpose PI3K/AKT pathway alterations are frequent in hormone receptor-positive (HR+) breast cancers. IPATunity130 Cohort B investigated ipatasertib–paclitaxel in PI3K pathway-mutant HR+ unresectable locally advanced/metastatic breast cancer (aBC). Methods Cohort B of the randomized, double-blind, placebo-controlled, phase 3 IPATunity130 trial enrolled patients with HR+ HER2-negative PIK3CA/AKT1/PTEN-altered measurable aBC who were considered inappropriate for endocrine-based therapy (demonstrated insensitivity to endocrine therapy or visceral crisis) and were candidates for taxane monotherapy. Patients with prior chemotherapy for aBC or relapse 2, days 1, 8, 15), every 28 days until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed progression-free survival (PFS). Results Overall, 146 patients were randomized to ipatasertib–paclitaxel and 76 to placebo–paclitaxel. In both arms, median investigator-assessed PFS was 9.3 months (hazard ratio, 1.00, 95% CI 0.71–1.40) and the objective response rate was 47%. Median paclitaxel duration was 6.9 versus 8.8 months in the ipatasertib–paclitaxel versus placebo–paclitaxel arms, respectively; median ipatasertib/placebo duration was 8.0 versus 9.1 months, respectively. The most common grade ≥ 3 adverse events were diarrhea (12% with ipatasertib–paclitaxel vs 1% with placebo–paclitaxel), neutrophil count decreased (9% vs 7%), neutropenia (8% vs 9%), peripheral neuropathy (7% vs 3%), peripheral sensory neuropathy (3% vs 5%) and hypertension (1% vs 5%). Conclusion Adding ipatasertib to paclitaxel did not improve efficacy in PIK3CA/AKT1/PTEN-altered HR+ HER2-negative aBC. The ipatasertib–paclitaxel safety profile was consistent with each agent’s known adverse effects. Trial registration NCT03337724.

Purpose To determine and compare the sensitivity, specificity, and proportion of patients eligible for discharge by the Brain Injury Guidelines and the Mild TBI Risk Score in patients with mild traumatic brain injury and concomitant intracranial injury. Methods Retrospective review of the medical records of adult patients with traumatic intracranial injuries and an initial Glasgow Coma Scale score of 14–15, who sought care at Helsingborg Hospital between 2014/01/01 and 2019/12/31. Both guidelines were theoretically applied. The sensitivity, specificity, and percentage of the cohort that theoretically could have been discharged by either guideline were calculated. The outcome was defined as death, in-hospital intervention, admission to the intensive care unit, requiring emergency intubation due to intracranial injury, decreased consciousness, or seizure within 30 days of presentation. Results Of the 538 patients included, 8 (1.5%) and 10 (1.9%) were eligible for discharge according to the Brain Injury Guidelines and the Mild TBI Risk Score, respectively. Both guidelines had a sensitivity of 100%. The Brain Injury Guidelines had a specificity of 2.3% and the Mild TBI Risk Score had a specificity of 2.9%. Conclusion There was no difference between the two guidelines in sensitivity, specificity, or proportion of the cohort eligible for discharge. Specificity and proportion of cohort eligible for discharge were lower than each guideline’s original study. At present, neither guideline can be recommended for implementation in the current or similar settings.

Whether surgical revascularization can prevent recurrent hemorrhage in hemorrhagic moyamoya disease (HMD) patients remains a matter of debate. This study mainly aims at the comparison of treatment effect between surgical revascularization and conservative treatment of adult HMD patients. We retrospectively enrolled 322 adult HMD patients, including 133 in revascularization group and 189 in conservative group. The revascularization group included patients who underwent combined (n = 97) or indirect revascularization alone (n = 36). Ninety-two and forty-one patients underwent unilateral and bilateral revascularization respectively. The modified Rankin scale (mRS) was used to assess the functional status. The comparison was made based on initial treatment paradigm among two categories: (1) revascularization vs. conservative, (2) unilateral vs. bilateral revascularization. The rebleeding rate was significantly lower in revascularization group than that in conservative group (14.3% vs. 27.0%, P = 0.007). As for the functional outcomes, the average mRS was significantly better in revascularization group (1.7 ± 1.5) than that in conservative group (2.8 ± 1.9) (P

OBJECTIVES To elicit antibiotic prescribing patterns across Indian Pediatric Intensive Care Units (PICU) and assess attributes of the antibiotic stewardship programs. METHODS A link to a web-based questionnaire was sent by email to pediatric intensivists across India. RESULTS Responses were received from 62 PICUs. Majority of respondents were from private hospitals [49/62 (79.5%)]. The most commonly reported infection requiring PICU admission was community-acquired pneumonia [by 39 (62.9%) PICUs] followed by gastroenteritis [26 (41.9%)], and meningitis [15 (24.1%)]. The blood culture positivity rates varied among participating PICUs with 37 centers (59.6%) reporting low blood culture positivity yield (

BACKGROUND Techniques of retromuscular repair of ventral hernias aim at avoiding complications linked to intraperitoneal patch. Aim of the study was to evaluate results of the VTEP technique. METHODS On 187 patients who underwent a VTEP, evaluation was carried out on 128 patients with a minimum follow-up of 1 year. The surgical technique consisted of creating connection between both retro-rectus spaces, by division of the medial edges of the posterior sheath and deploying the patch in the retromuscular patch without fixation. The posterior sheath was repaired in 16 cases. The patients were sent a questionnaire and invitation to have physical examination by the surgeon. RESULTS The mean hernia and patch size were 9 (1-50) and 225 (50-500) cm2, respectively. The mean follow-up was 21.2 (12-35) months; 120 (93.7%) patients were evaluated, 21 by physical examination, 41 by questionnaire, 58 by telephone and 8 (6.3%) were lost to follow-up. Hundred (83%) patients felt no pain at rest, and 88 (73%) during effort. Among patients who felt some degree of pain, the mean VAS value was 2 (1-4) at rest and 2.6 (1-7) during effort. Two recurrences occurred, 3 patients were worried about a persisting diastasis bulging at the upper border of the patch and 8 patients in which the posterior sheath was not repaired complained they felt that their upper abdomen was somewhat distended or swollen. CONCLUSION The VTEP procedure provides a low level of chronic pain but can entail some drawbacks, such as the swollen abdomen, which can be attributed to the absence of repair of the posterior sheath. It may be that restoring or preserving structural integrity of the abdominal belt formed by the posterior sheath constitutes a key point in retromuscular techniques.

OBJECTIVES Men have been regarded as critical partners in promoting maternal health and improving pregnancy outcomes, still men have not been able to provide these supports holistically during pregnancy due to the patriarchal nature of many Nigerian societies and dynamics in gender roles. There is a dearth of studies in Nigeria that have investigated the social support spouse provide during pregnancy. This study investigated the perspectives of women about the social support provided by men during pregnancy and factors that could influence or promote these support. METHODS Forty one consenting women who were purposively selected in six primary health centers that offer ANC services in Ibadan participated in the six focus group discussions; participants ranged from 6 to 8 in each group. Transcripts from audio recordings were analyzed using thematic analysis; similar and dissimilar themes within groups and across groups were categorized. RESULTS Discussants highlighted ways of providing social support mainly as assisting with household chores and taking care of other children. None of the discussants stated accompanying to antenatal clinic by their spouses as a way social support was provided during pregnancy. Almost all the women highlighted that social support provided by men changes as pregnancy advances but the changes were dependent on the number of children. CONCLUSIONS Community education and male friendly sessions are encouraged to promote men's participation and engagement during pregnancy.

BACKGROUND The currently utilized International Neuroblastoma Risk Group (INRG) staging system developed in 2009 uses image-defined risk factors as a measure of surgical risk, separating resectable neuroblastoma from those best preceded by chemotherapy. The previous International Neuroblastoma Staging System was based primarily on surgical findings. We hypothesized there would be a change to the role of the surgeon in neuroblastoma treatment in the more recent decade. METHODS This is a single center 20-year retrospective analysis of 104 patients with International Classification of Diseases-9 and -10 codes for neuroblastoma. Patient demographics, tumor site, cancer treatment modality, survival, biopsy technique, surgical intervention, and pathology staging were collected. Data was analyzed by analysis of variance (ANOVA) and Student's t test. RESULTS There was a decrease in open surgeries for extra-adrenal neuroblastomas in the later decade (77%, 31%, P = 0.01). There was a narrowing of the time interval to surgery in the later cohort, likely as a result of uniformity in surgical timing on treatment protocols relying on INRG staging. CONCLUSIONS Our findings mirror changes in practice patterns globally. We found an increase in minimally invasive approaches but did not find a difference in the role of the surgeon under the INRG staging system.

Hypertension is the most common cardiovascular risk factor for acute cardiovascular outcomes, including acute coronary disease, stroke, chronic kidney disease and congestive heart failure. Despite the fact that it represents the most prevalent risk factor in the general population, mostly in elderly individuals, its awareness is still relatively low, being about one third of patients living with undiagnosed hypertension and high risk of experiencing acute cardiovascular events. In addition, though recent improvement in pharmacological and non-pharmacological therapeutic options, hypertension is largely uncontrolled, with about 35–40% of treated hypertensive patients achieving the recommended therapeutic targets. Among different modern interventions proposed for improving blood pressure control in treated hypertensive patients, a systematic adoption of home BP monitoring has demonstrated to be one of the most effective. Indeed, it improves patients’ awareness of the disease and adherence to prescribed medications and allows tailoring and personalizing BP lowering therapies. Home BP monitoring is particularly suitable for telemedicine and mobile-health solutions. Indeed, in specific conditions, when face-to-face interactions between patients and physicians are not allowed or even suspended, as in case of COVID-19 pandemic, telemedicine may ensure effective management of hypertension, as well as other cardiovascular and non-cardiovascular comorbidities. This review will summarize strengths and limitations of telemedicine in the clinical management of hypertension with a particular focus on the lessons learned during the COVID-19 pandemic.

BACKGROUND Dynamic contrast-enhanced magnetic resonance imaging (MRI) of the liver in pediatric Fontan patients often shows peripheral reticular areas of hypoenhancement, which has not been studied in detail. OBJECTIVE To semiquantitatively score the hepatic MR perfusion abnormality seen in pediatric Fontan patients, and to correlate the perfusion abnormality with functional clinical and hemodynamic parameters. MATERIALS AND METHODS All children (

Alcohol misuse is common in many societies worldwide and is associated with extensive morbidity and mortality, often leading to alcohol use disorders (AUD) and alcohol-related end-organ damage. The underlying mechanisms contributing to the development of AUD are largely unknown; however, growing evidence suggests that alcohol consumption is strongly associated with alterations in DNA methylation. Identification of alcohol-associated methylomic variation might provide novel insights into pathophysiology and novel treatment targets for AUD. Here we performed the largest single-cohort epigenome-wide association study (EWAS) of alcohol consumption to date (N = 8161) and cross-validated findings in AUD populations with relevant endophenotypes, as well as alcohol-related animal models. Results showed 2504 CpGs significantly associated with alcohol consumption (Bonferroni p value < 6.8 × 10−8) with the five leading probes located in SLC7A11 (p = 7.75 × 10−108), JDP2 (p = 1.44 × 10−56), GAS5 (p = 2.71 × 10−47), TRA2B (p = 3.54 × 10−42), and SLC43A1 (p = 1.18 × 10−40). Genes annotated to associated CpG sites are implicated in liver and brain function, the cellular response to alcohol and alcohol-associated diseases, including hypertension and Alzheimer’s disease. Two-sample Mendelian randomization confirmed the causal relationship of consumption on AUD risk (inverse variance weighted (IVW) p = 5.37 × 10−09). A methylation-based predictor of alcohol consumption was able to discriminate AUD cases in two independent cohorts (p = 6.32 × 10−38 and p = 5.41 × 10−14). The top EWAS probe cg06690548, located in the cystine/glutamate transporter SLC7A11, was replicated in an independent cohort of AUD and control participants (N = 615) and showed strong hypomethylation in AUD (p −17). Decreased CpG methylation at this probe was consistently associated with clinical measures including increased heavy drinking days (p −4), increased liver function enzymes (GGT (p = 1.03 × 10−21), ALT (p = 1.29 × 10−6), and AST (p = 1.97 × 10−8)) in individuals with AUD. Postmortem brain analyses documented increased SLC7A11 expression in the frontal cortex of individuals with AUD and animal models showed marked increased expression in liver, suggesting a mechanism by which alcohol leads to hypomethylation-induced overexpression of SLC7A11. Taken together, our EWAS discovery sample and subsequent validation of the top probe in AUD suggest a strong role of abnormal glutamate signaling mediated by methylomic variation in SLC7A11. Our data are intriguing given the prominent role of glutamate signaling in brain and liver and might provide an important target for therapeutic intervention.

The hypothesis of the psychosis continuum enables to study the mechanisms of psychosis risk not only in clinical samples but in non-clinical as well. The aim of this longitudinal study was to investigate self-disturbances (SD), a risk factor that has attracted substantial interest over the last two decades, in combination with trauma, cognitive biases and personality, and to test whether SD are associated with subclinical positive symptoms (PS) over a 12-month follow-up period. Our study was conducted in a non-clinical sample of 139 Polish young adults (81 females, age M = 25.32, SD = 4.51) who were selected for frequent experience of subclinical PS. Participants completed self-report questionnaires for the evaluation of SD (IPASE), trauma (CECA.Q), cognitive biases (DACOBS) and personality (TCI), and were interviewed for subclinical PS (CAARMS). SD and subclinical PS were re-assessed 12 months after baseline measurement. The hypothesized model for psychosis risk was tested using path analysis. The change in SD and subclinical PS over the 12-month period was investigated with non-parametric equivalent of dependent sample t-tests. The models with self-transcendence (ST) and harm avoidance (HA) as personality variables were found to be well-fitted and explained 34% of the variance in subclinical PS at follow-up. Moreover, we found a significant reduction of SD and subclinical PS after 12 months. Our study suggests that combining trauma, cognitive biases, SD and personality traits such as ST and HA into one model can enhance our understanding of appearance as well as maintenance of subclinical PS.

Background To examine published data and assess evidence relating to safety and efficacy of surgical management of symptomatic pineal cysts without hydrocephalus (nhSPC), we performed a systematic review of the literature and meta-analysis. Methods Following the PRISMA guidelines, we searched Pubmed and SCOPUS for all reports with the query ‘Pineal Cyst’ AND ‘Surgery’ as of March 2021, without constraints on study design, publication year or status (PROSPERO_CRD:42,021,242,517). Assessment of 1537 hits identified 26 reports that met inclusion and exclusion criteria. Results All 26 input studies were either case reports or single-centre retrospective cohorts. The majority of outcome data were derived from routine physician-recorded notes. A total of 294 patients with surgically managed nhSPC were identified. Demographics: Mean age was 29 (range: 4–63) with 77% females. Mean cyst size was 15 mm (5–35). Supracerebellar-infratentorial approach was adopted in 90% of cases, occipital-transtentorial in 9%, and was not reported in 1%. Most patients were managed by cyst resection (96%), and the remainder by fenestration. Mean post-operative follow-up was 35 months (0–228). Presentation: Headache was the commonest symptom (87%), followed by visual (54%), nausea/vomit (34%) and vertigo/dizziness (31%). Other symptoms included focal neurology (25%), sleep disturbance (17%), cognitive impairment (16%), loss of consciousness (11%), gait disturbance (11%), fatigue (10%), ‘psychiatric’ (2%) and seizures (1%). Mean number of symptoms reported at presentation was 3 (0–9). Outcomes: Improvement rate was 93% (to minimise reporting bias only consecutive cases from cohort studies were considered, N = 280) and was independent of presentation. Predictors of better outcomes were large cyst size (OR = 5.76; 95% CI: 1.74–19.02) and resection over fenestration (OR = 12.64; 3.07–52.01). Age predicted worse outcomes (OR = 0.95; 0.91–0.99). Overall complication rate was 17% and this was independent of any patient characteristics. Complications with long-term consequences occurred in 10 cases (3.6%): visual disturbance (3), chronic incisional pain (2), sensory disturbance (1), fatigue (1), cervicalgia (1), cerebellar stroke (1) and mortality due to myocardial infarction (1). Conclusions Although the results support the role of surgery in the management of nhSPCs, they have to be interpreted with a great deal of caution as the current evidence is limited, consisting only of case reports and retrospective surgical series. Inherent to such studies are inhomogeneity and incompleteness of data, selection bias and bias related to assessment of outcome carried out by the treating surgeon in the majority of cases. Prospective studies with patient-reported and objective outcome assessment are needed to provide higher level of evidence.