Effects of hip joint kinematics on the effective pelvis stiffness and hip impact force during simulated sideways falls.

Improved understanding is required on how hip fracture risk is influenced by landing configuration. We examined how hip impact dynamics was affected by hip joint kinematics during simulated sideways falls. Twelve young adults (7 males, 5 females) of mean age 23.5 (SD = 1.5) years, participated in pelvis release experiments. Trials were acquired with the hip flexed 15° and 30° for each of three hip rotations: +15° ("external rotation"), 0°, and -15° ("internal rotation"). During falls, force-deformation data of the pelvis were recorded. Outcome variables included the peak hip impact force (Fexperimental) and effective stiffness of the pelvis (k1st, ksecant, and kms) determined with different methods suggested in literature, and predicted hip impact force during a fall from standing height (F1st, Fsecant and Fms). The two-way repeated-measures ANOVA was used to test whether these variables were associated with hip joint angles. The Fexperimental, ksecant and Fsecant were associated with hip rotation (F = 5.587, p = 0.005; F = 9.278, p < 0.0005; F = 5.778, p = 0.004, respectively), and 15 %, 31 % and 17 % smaller in 15° external than internal rotation (848 versus 998 N; 24.6 versus 35.6 kN/m; 2,637 versus 3,170 N, respectively). However, none of the outcome variables were associated with hip flexion (p > 0.05). Furthermore, there were no interactions between the hip rotation and flexion for all outcome variables (p > 0.05). Our results provide insights on hip impact dynamics, which may help improve a hip model to assess hip fracture risk during a fall.

Magnetocardiography at rest predicts cardiac death in patients with acute chest pain.

Introduction: Sudden cardiac arrest is a major cause of morbidity and mortality worldwide and remains a major public health problem for which better non-invasive prediction tools are needed. Primary preventive therapies, such as implantable cardioverter defibrillators, are not personalized and not predictive. Most of these devices do not deliver life-saving therapy during their lifetime. The individual relationship between fatal arrhythmias and cardiac function abnormalities in predicting cardiac death risk has rarely been explored. Methods: We retrospectively analyzed the measurements at rest for 191 patients with acute chest pain (ACP) magnetocardiographically. Our recently introduced analyses are able to detect inhomogeneities of the depolarization and repolarization. Moreover, electrically silent phenomena-intracellular ionic currents as well as vortex currents-can be measured and quantified. All included ACP patients were recruited in 2009 at Yonsei University Hospital and were followed up until 2022. Results: During half of the follow-up period (6.5 years), 11 patients died. Out of all the included nine clinical, eight magnetocardiographical, and nine newly introduced magnetoionographical parameters we tested in this study, three parameters revealed themselves to be outstanding at predicting death: heart rate-corrected QT (QTc) prolongation, depression of repolarization current IKr + IKs, and serum creatinine (all significant in Cox regression, p < 0.05). They clearly predicted cardiac death over the 6.5 years duration (sensitivity 90.9%, specificity 85.6%, negative predictive accuracy 99.4%). Cardiac death risk was more than ninefold higher in patients with low repolarization reserve and QTc prolongation in comparison with the remaining patients with ACP (p < 0.001). The non-parametric Kaplan-Meier statistics estimated significantly lower survival functions from their lifetime data (p < 0.001). Discussion: To the best of our knowledge, these are the first data linking magnetocardiographical and magnetoionographical parameters and subsequent significant fatal events in people, suggesting structural and functional components to clinical life-threatening ventricular arrhythmogenesis. The findings support investigation of new prevention strategies and herald those new non-invasive techniques as complementary risk stratification tools.

Cardiac magnetic field map topology quantified by Kullback-Leibler entropy identifies patients with clinically suspected myocarditis.

Background: Myocarditis is a condition that can have severe adverse outcomes and lead to sudden cardiac death if remaining undetected. This study tested the capability of cardiac magnetic field mapping to detect patients with clinically suspected myocarditis. This could open up the way for rapid, non-invasive, and cost-effective screening of suspected cases before a gold standard assessment via endomyocardial biopsy. Methods: Historical cardiac magnetic field maps (n = 97) and data from a state-of-the-art magnetocardiography device (n = 30) were analyzed using the Kullback-Leibler entropy (KLE) for dimensionality reduction and topological quantification. Linear discriminant analysis was used to discern between patients with ongoing myocarditis and healthy controls. Results: The STT segment of a magnetocardiogram, i.e., the section between the end of the S wave and the end of the T wave, was best suited to discern both groups. Using a 250-ms excerpt from the onset of the STT segment gave a reliable classification between the myocarditis and control group for both historic data (sensitivity: 0.83, specificity: 0.85, accuracy: 0.84) and recent data (sensitivity: 0.69, specificity: 0.88, accuracy: 0.80) using the KLE to quantify the topology of the cardiac magnetic field map. Conclusion: The implementation based on KLE can reliably distinguish between clinically suspected myocarditis patients and healthy controls. We implemented an automatized feature selection based on LDA to replace the observer-dependent manual thresholding in previous studies.

Effects of hip muscle activation on the stiffness and energy absorption of the trochanteric soft tissue during impact in sideways falls.

The trochanteric soft tissue attenuates impact force or absorbs impact energy during a fall on the hip (thereby helps to reduce a risk of hip fracture). While the benefits should be affected by contractions of muscles spanning the hip joint, no information is available to date. We examined how the stiffness (force attenuation capacity) and energy absorption of the trochanteric soft tissue were affected by hip muscle activation during a fall. Thirteen healthy young individuals (5 males, 8 females) participated in the pelvis release experiment. Falling trials were acquired with three muscle contraction conditions: 0-20% ("relaxed"), 20-50% ("moderate"), and 60-100% ("maximal") of the maximal voluntary isometric contraction of the gluteus medius muscle. During trials, we measured real-time force and deformation behaviour of the trochanteric soft tissue. Outcome variables included the stiffness and energy absorption of the soft tissue. The stiffness and energy absorption ranged from 56.1 to 446.9 kN/m, and from 0.15 to 2.26 J, respectively. The stiffness value increased with muscle contraction, and 59% greater in "maximal" than "relaxed" condition (232.2 (SD = 121.4) versus 146.1 (SD = 49.9)). However, energy absorption decreased with muscle contraction, and 58.9% greater in "relaxed" than "maximal" condition (0.89 (SD = 0.63) versus 0.56 (SD = 0.41)). Our results provide insights on biomechanics of the trochanteric soft tissue ("natural" padding device) during impact stage of a fall, suggesting that soft tissues' protective benefits are largely affected by the level of muscle contraction.

Resection of the femoral neck: a new technique for the treatment of mallory type I intraoperative femoral fracture during total hip arthroplasty.

Intraoperative femoral fracture is a common complication during cementless total hip arthroplasty (THA). Cerclage wiring has been used for this type of fractures to attain intraoperative stability of the femoral stem. We designed a new technique to treat Mallory type 1 intraoperative femoral fractures. We excised fractured femoral neck fragment and without additional fixation and lightly tapped down the femoral stem to obtain a tight contact to the femoral cortex at the subtrochanteric level. In this case series, we described this technique and reported its outcomes. From January 2015 to December 2017, 600 cementless THAs (557 patients) were done with use of a proximally coated tapered stem design at our department. Among the 600 THAs, Mallory type 1 intraoperative femoral fracture occurred in 8 hips (8 patients), and all of them were treated with the excision of the fractured femoral neck. Mean age of the 8 patients was 58.1 years (range, 30.4 to 81.3 years) at the time of surgery. We report the results of this new technique at postoperative 2 to 5 years (mean, 3.4 years). All stems were placed in the neutral position. There was no revision and no stem showed any evidence of subsidence or loosening during the follow-up. The mean Harris hip score was 85.9 points at the latest follow-up. We recommend to use the femoral neck excision technique for the treatment of Mallory type 1 intraoperative femoral fractures.

Anterior resection syndrome: a randomized clinical trial of a 5-HT3 receptor antagonist (ramosetron) in male patients with rectal cancer.

BACKGROUND: No effective treatment exists for anterior resection syndrome (ARS) following sphincter-saving surgery for rectal cancer. This RCT assessed the safety and efficacy of a 5-HT3 receptor antagonist, ramosetron, for ARS. METHODS: A single-centre, randomized, controlled, open-label, parallel group trial was conducted. Male patients with ARS 1 month after rectal cancer surgery or ileostomy reversal were enrolled and randomly assigned (1 : 1) to 5 µg of ramosetron (Irribow®) daily or conservative treatment for 4 weeks. Low ARS (LARS) score was calculated after randomization and 4 weeks after treatment. The study was designed as a superiority test with a primary endpoint of the proportion of patients with major LARS between the groups. Primary outcome analysis was based on the modified intention-to-treat population. Safety was assessed by monitoring adverse events during the study. RESULTS: : A total of 100 patients were randomized to the ramosetron (49 patients) or conservative treatment group (51 patients). Two patients were excluded, and 48 and 50 patients were analysed in the ramosetron and control groups, respectively. The proportion of major LARS after 4 weeks was 58 per cent (28 of 48 patients) in the ramosetron group versus 82 per cent (41 of 50 patients) in the control group, with a difference of 23.7 per cent (95 per cent c.i. 5.58 to 39.98, P = 0.011). There were minor adverse events in five patients, which were hard stool, frequent stool or anal pain. These were not different between the two groups. There were no serious adverse events. CONCLUSION: : Ramosetron could be safe and feasible for male patients with ARS. TRIAL REGISTRATION NUMBER: NCT02869984 (http://www.clinicaltrials.gov).

A study of the microbiological profile of filler-induced skin necrosis.

Skin necrosis is one of the most severe complications following filler injections, and can result in permanent aesthetic defects. Although an increasing number of studies have addressed the management of dermal filler complications, no study has described the spectrum of microbial pathogens. The aim of this study was to delineate the bacterial profile and prognostic factors of filler-related skin necrosis by reviewing the clinical and microbiological features of these patients. A retrospective medical record review of patients undergoing treatment for skin necrosis induced by fillers was conducted. In total, 10 cases were identified, with injection sites being the nasolabial fold (70%; n = 7), nasal dorsum (20%; n = 2) and nasal tip (10%; n = 1). Reviewing the culture results, the true culture-positive rate was found to be 50% after cases of contamination were excluded. To avoid permanent sequelae, all physicians should be aware of possible secondary infections when treating filler-induced skin necrosis.

FAST: a randomised phase II study of zolbetuximab (IMAB362) plus EOX versus EOX alone for first-line treatment of advanced CLDN18.2-positive gastric and gastro-oesophageal adenocarcinoma.

BACKGROUND: Claudin 18.2 (CLDN18.2) is contained within normal gastric mucosa epithelial tight junctions; upon malignant transformation, CLDN18.2 epitopes become exposed. Zolbetuximab, a chimeric monoclonal antibody, mediates specific killing of CLDN18.2-positive cells through immune effector mechanisms. PATIENTS AND METHODS: The FAST study enrolled advanced gastric/gastro-oesophageal junction and oesophageal adenocarcinoma patients (aged ≥18 years) with moderate-to-strong CLDN18.2 expression in ≥40% tumour cells. Patients received first-line epirubicin + oxaliplatin + capecitabine (EOX, arm 1, n = 84) every 3 weeks (Q3W), or zolbetuximab + EOX (loading dose, 800 mg/m2 then 600 mg/m2 Q3W) (arm 2, n = 77). Arm 3 (exploratory) was added after enrolment initiation (zolbetuximab + EOX 1000 mg/m2 Q3W, n = 85). The primary endpoint was progression-free survival (PFS) and overall survival (OS) was a secondary endpoint. RESULTS: In the overall population, both PFS [hazard ratio (HR) = 0.44; 95% confidence interval (CI), 0.29-0.67; P < 0.0005] and OS (HR = 0.55; 95% CI, 0.39-0.77; P < 0.0005) were significantly improved with zolbetuximab + EOX (arm 2) compared with EOX alone (arm 1). This significant PFS benefit was retained in patients with moderate-to-strong CLDN18.2 expression in ≥70% of tumour cells (HR = 0.38; 95% CI, 0.23-0.62; P < 0.0005). Significant improvement in PFS was also reported in the overall population of arm 3 versus arm 1 (HR = 0.58; 95% CI, 0.39-0.85; P = 0.0114) but not in high CLDN18.2-expressing patients; no significant improvement in OS was observed in either population. Most adverse events (AEs) related to zolbetuximab + EOX (nausea, vomiting, neutropenia, anaemia) were grade 1-2. Grade ≥3 AEs showed no substantial increases overall (zolbetuximab + EOX versus EOX alone). CONCLUSIONS: In advanced gastric/gastro-oesophageal junction and oesophageal adenocarcinoma patients expressing CLDN18.2, adding zolbetuximab to first-line EOX provided longer PFS and OS versus EOX alone. Zolbetuximab + EOX was generally tolerated and AEs were manageable. Zolbetuximab 800/600 mg/m2 is being evaluated in phase III studies based on clinical benefit observed in the overall population and in patients with moderate-to-strong CLDN18.2 expression in ≥70% of tumour cells.

Investigation of the optimal medium and application strategy for foot-and-mouth disease vaccine antigen production.

AIMS: For the effective production of 146S particles, which determines foot-and-mouth disease (FMD) vaccine efficacy, we aimed to identify the optimal medium that is easy-to-use, productive and economically affordable for the large-scale production of FMD vaccine. METHODS AND RESULTS: Nine combinations of cell growth media and replacement media were tested for virus propagation. Apart from the replacement strategy, we tested a simple addition strategy involving the addition of 30% v/v of fresh medium to the total spent medium using the Cellvento BHK-200 (Vento). Unlike other tested media that produced poor yields of 146S particles when the spent media were not eliminated, Vento exhibited high productivity with the 30% addition strategy. CONCLUSIONS: Considering its lower price and media consumption compared to those of other media that require media replacement, the 30% addition strategy of Vento is highly effective. Furthermore, owing to its simple application strategy, it makes the scale-up process easy and helps in saving the time and labour involved in spent media removal. SIGNIFICANCE AND IMPACT OF THE STUDY: Through the first comparative assessment of commercial media for the 146S particle recovery, this study suggests the best practical medium for the industrial-scale production of FMD vaccines.

Short-term outcomes of pediatric laparoscopic inguinal hernia repair in Korea based on Korean Health Insurance Big Data: 2011-2015.

PURPOSE: For pediatric inguinal hernia repairs (IHRs), open IHR (high ligation) has long been a gold standard. Recently laparoscopic IHR (LIHR) was introduced as a new treatment modality and has been performed more frequently in Korea. Unlike adults, LIHR in children is still controversial. In the present study, we investigate the short-term outcomes of pediatric LIHR in Korea using nationwide inpatient data. METHODS: We analyzed clinical practice for IHRs from 2011 to 2015 using Korean Health Insurance Review and Assessment Service-National Inpatient Sample. RESULTS: A total of 5281 patients 15 years old or younger underwent 5356 IHRs: 4507 OIHRs and 849 LIHRs. M:F ratio was 2.4:1. The proportion of LIHRs was only 1.8% at the beginning but had been continuously increased up to 29.8% at the end of the study period. LIHRs were closely related to synchronous bilateral inguinal hernia repairs (SBIHRs). Overall, SBIHRs were performed in 10.9% of open and 49.2% of LIHRs. Metachronous contralateral IHRs (MCIHRs) after initial unilateral IHRs were significantly more frequent after OIHRs (1.7%, 69/3, 951) than after LIHRs (0.2%, 1/427). Recurrence rate per side during study period was 0.1% (6/4, 993) after OIHRs and 0.2% (2/1, 259) after LIHRs, respectively (statistically insignificant). CONCLUSION: Nationwide inpatient data showed that LIHRs in pediatric patients had recently been increasingly performed in Korea. LIHRs facilitated SBIHRs, which, in turn, decreased the needs of MCIHRs. However limited numbers of patients might actually have benefited from them. Early recurrence after primary IHRs in children is quite low regardless of way of approach.

Systemic contact dermatitis induced by Rhus allergens in Korea: exercising caution in the consumption of this nutritious food.

Systemic contact dermatitis (SCD) develops when a person who was previously sensitized to an allergen is exposed to the same allergen via the systemic route. In East Asia, the use of lacquer for polishing furniture is common and a part of the traditional culture. Contact exposure to tableware polished with Rhus lacquer may lead to sensitization. In Korea, SCD is commonly observed after systemic exposure to Rhus, a nutritious food item consumed because of the common belief of it improving the immune system. In this study, we reviewed the medical records of 21 Korean patients with SCD caused by Rhus ingestion. We found that the most significant epidemiological factor for SCD was the season of the year. Furthermore, 66.67% of the patients presented with leucocytosis and 23.81% showed increased liver enzyme levels. It is important to educate people on the risks associated with the systemic ingestion of Rhus.

Sequentially addressable dielectrophoretic array for high-throughput sorting of large-volume biological compartments.

Droplet microfluidics has become a powerful tool in precision medicine, green biotechnology, and cell therapy for single-cell analysis and selection by virtue of its ability to effectively confine cells. However, there remains a fundamental trade-off between droplet volume and sorting throughput, limiting the advantages of droplet microfluidics to small droplets (<10 pl) that are incompatible with long-term maintenance and growth of most cells. We present a sequentially addressable dielectrophoretic array (SADA) sorter to overcome this problem. The SADA sorter uses an on-chip array of electrodes activated and deactivated in a sequence synchronized to the speed and position of a passing target droplet to deliver an accumulated dielectrophoretic force and gently pull it in the direction of sorting in a high-speed flow. We use it to demonstrate large-droplet sorting with ~20-fold higher throughputs than conventional techniques and apply it to long-term single-cell analysis of Saccharomyces cerevisiae based on their growth rate.

HELP-(Heparin-induced Extracorporeal LDL Precipitation)-apheresis in heart recipients with cardiac allograft vasculopathy and concomitant hypercholesterolemia: Influence of long-term treatment on the microcirculation.

Hyperlipidemic heart transplant patients who develop cardiac allograft vasculopathy (CAV) benefit from HELP-apheresis (Heparin-induced Extracorporeal LDL Precipitation) which enables drastic lowering of plasma low-density lipoprotein, lipoprotein (a), and fibrinogen. There is evidence that HELP-apheresis also improves microcirculation by an immediate improvement of impaired endothelial-dependent vasodilatation and additive hemorheological effects.Therefore, cutaneous microcirculation was examined before, during, and after the first HELP-apheresis in eight hyperlipidemic cardiac transplant recipients with CAV. To study the long-term effect the intravital microscopy was repeated after three and 12 months of weekly apheresis treatment.In CAV patients the baseline mean erythrocyte velocity was pathologically reduced with 0.13±0.07 mm/s. During the first HELP-apheresis the erythrocyte velocity increased significantly (p = 0.0001) and remained increased until the end of the HELP procedure (p < 0.05). After three months of weekly apheresis treatment a decrease of temporary flow stops in the capillaries with a progressive homogenization (concordance) of the cutaneous microcirculation was observed. After one year of weekly treatment a markedly increase in mean erythrocyte velocity under resting conditions occurred. In addition, a reactive post-ischemic hyperemia could be established for the first time.Even the first single HELP-apheresis resulted in a significant improvement of the cutaneous microcirculation. The long-term treatment of these patients resulted in a marked improvement of the cutaneous microcirculation with the tendency to a normalization of the regulation of the capillary perfusion.

Correction to: CD4 T cell count is positively associated with lumbar spine bone mass in HIV-infected men under the age of 50 years.

Two sentences in the Discussion section were incorrect.

A multicentre, phase IIa study of zolbetuximab as a single agent in patients with recurrent or refractory advanced adenocarcinoma of the stomach or lower oesophagus: the MONO study.

BACKGROUND: Claudin 18.2 (CLDN18.2) is physiologically confined to gastric mucosa tight junctions; however, upon malignant transformation, perturbations in cell polarity lead to CLDN18.2 epitopes being exposed on the cancer cell surface. The first-in-class monoclonal antibody, zolbetuximab (formerly known as IMAB362), binds to CLDN18.2 and can induce immune-mediated lysis of CLDN18.2-positive cells. PATIENTS AND METHODS: Patients with advanced gastric, gastro-oesophageal junction (GEJ) or oesophageal adenocarcinomas with moderate-to-strong CLDN18.2 expression in ≥50% of tumour cells received zolbetuximab intravenously every 2 weeks for five planned infusions. At least three patients were enrolled in two sequential cohorts (cohort 1300 mg/m2; cohort 2600 mg/m2); additional patients were enrolled into a dose-expansion cohort (cohort 3600 mg/m2). The primary end point was the objective response rate [ORR: complete and partial response (PR)]; secondary end points included clinical benefit [ORR+stable disease (SD)], progression-free survival, safety/tolerability, and zolbetuximab pharmacokinetic profile. RESULTS: From September 2010 to September 2012, 54 patients were enrolled (cohort 1, n = 4; cohort 2, n = 6; cohort 3, n = 44). Three patients in cohort 1 and 25 patients in cohorts 2/3 received at least 5 infusions. Antitumour activity data were available for 43 patients, of whom 4 achieved PR (ORR 9%) and 6 (14%) had SD for a clinical benefit rate of 23%. In a subgroup of patients with moderate-to-high CLDN18.2 expression in ≥70% of tumour cells, ORR was 14% (n = 4/29). Treatment-related adverse events occurred in 81.5% (n = 44/54) patients; nausea (61%), vomiting (50%), and fatigue (22%) were the most frequent. CONCLUSIONS: Zolbetuximab monotherapy was well tolerated and exhibited antitumour activity in patients with CLDN18.2-positive advanced gastric or GEJ adenocarcinomas, with response rates similar to those reported for single-agent targeted agents in gastric/GEJ cancer trials. CLINICALTRIALS.GOV NUMBER: NCT01197885.

Influence of exposure to summer environments on skin properties.

BACKGROUND: Although cosmetic companies have launched products to combat extreme environments (hot or cold) and various pollutants, research into the effects of these conditions on skin properties is lacking. We aimed to investigate the influence of exposure to outdoor environments during summer on skin properties. METHODS: We enrolled 20 women in their 20s and 40s. They were exposed to outdoor and indoor environments for 90 min each in July 2016. Skin evaluations were performed on the face (forehead and cheek) and forearm. Skin hydration level, sebum secretion, trans-epidermal water loss (TEWL), pH and greasiness were evaluated. RESULTS: Skin hydration levels, sebum secretion, TEWL and greasiness in all examined regions were higher after outdoor exposure than after indoor exposure; however, skin pH decreased after outdoor exposure. Hydration levels on the forearm and sebum secretion on the face increased, whereas hydration levels and TEWL on the cheek, greasiness in all regions except the cheek, and pH in all regions decreased during the 90-min outdoor exposure. The hydration levels in all regions except the cheek, sebum secretion and greasiness on the face increased, but the TEWL and the pH declined after being indoors. CONCLUSION: Hot environments cause the production of more sweat, increasing hydration levels, sebum secretion, TEWL, and greasiness and reducing skin pH. After acclimatization, skin hydration on the cheek decreases because of sweat evaporation. Cosmetics that are marketed for use in summer should control sweat and sebum secretion, solve related inconveniences, and provide moisture, especially on the cheeks.