Electrical Stimulation-Based Twitch Exercise Suppresses Progression of Immobilization-Induced Muscle Fibrosis via Downregulation of PGC-1?/VEGF Pathway.

This study aimed to determine whether electrical stimulation-based twitch exercise is effective in inhibiting the progression of immobilization-induced muscle fibrosis. 19 Wistar rats were randomly divided into a control group (n=6), an immobilization group (n=6; with immobilization only), and a Belt group (n=7; with immobilization and twitch exercise through the belt electrode device, beginning 2 weeks after immobilization). The bilateral soleus muscles were harvested after the experimental period. The right soleus muscles were used for histological analysis, and the left soleus muscles were used for biochemical and molecular biological analysis. As a result, in the picrosirius red images, the perimysium and endomysium were thicker in both the immobilization and Belt groups compared to the control group. However, the perimysium and endomysium thickening were suppressed in the Belt group. The hydroxyproline content and alpha-SMA, TGF-beta1, and HIF-1alpha mRNA expressions were significantly higher in the immobilization and belt groups than in the control group. These expressions were significantly lower in the Belt group than in the immobilization group. The capillary-to-myofiber ratio and the mRNA expressions of VEGF and PGC-1alpha were significantly lower in the immobilization and belt groups than in the control group, these were significantly higher in the Belt group than in the immobilization group. From these results, Electrical stimulation-based twitch exercise using the belt electrode device may prevent the progression of immobilization-induced muscle fibrosis caused by downregulating PGC-1alpha/VEGF pathway, we surmised that this intervention strategy might be effective against the progression of muscle contracture. Keywords: Immobilization, Skeletal muscle, Fibrosis, Electrical stimulation-based twitch exercise, PGC-1alpha/VEGF pathway.

Skeletal Muscle Electrical Stimulation Prevents Progression of Disuse Muscle Atrophy via Forkhead Box O Dynamics Mediated by Phosphorylated Protein Kinase B and Peroxisome Proliferator-Activated Receptor gamma Coactivator-1alpha.

Although electrical muscle stimulation (EMS) of skeletal muscle effectively prevents muscle atrophy, its effect on the breakdown of muscle component proteins is unknown. In this study, we investigated the biological mechanisms by which EMS-induced muscle contraction inhibits disuse muscle atrophy progression. Experimental animals were divided into a control group and three experimental groups: immobilized (Im; immobilization treatment), low-frequency (LF; immobilization treatment and low-frequency muscle contraction exercise), and high-frequency (HF; immobilization treatment and high-frequency muscle contraction exercise). Following the experimental period, bilateral soleus muscles were collected and analyzed. Atrogin-1 and Muscle RING finger 1 (MuRF-1) mRNA expression levels were significantly higher for the experimental groups than for the control group but were significantly lower for the HF group than for the Im group. Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) mRNA and protein expression levels in the HF group were significantly higher than those in the Im group, with no significant differences compared to the Con group. Both the Forkhead box O (FoxO)/phosphorylated FoxO and protein kinase B (AKT)/phosphorylated AKT ratios were significantly lower for the Im group than for the control group and significantly higher for the HF group than for the Im group. These results, the suppression of atrogin-1 and MuRF-1 expression for the HF group may be due to decreased nuclear expression of FoxO by AKT phosphorylation and suppression of FoxO transcriptional activity by PGC-1alpha. Furthermore, the number of muscle contractions might be important for effective EMS.

Study of the electron-doping mechanism in single-walled carbon nanotubes using dimethylbenzimidazole.

Single-walled carbon nanotubes (SWCNTs) exhibit p-type properties in air, necessitating electron doping using n-dopants (e.g., reducing agents) for the development of SWCNT-based electronic devices. Dimethylbenzimidazole (DMBI-H) derivatives serve as effective electron dopants, not only for SWCNTs, but also for various organic semiconducting materials. However, the doping reaction is still a subject of debate. In this study, the electron-doping reactions of ortho-methoxy-substituted DMBI-H for SWCNTs were analyzed in protic and aprotic solvents in the presence and absence of dioxygen (O2). The presence of O2 was found to cause the reduction of O2 on the SWCNT surface in the protic solvent, resulting in the production of DMBI cations and water through proton-coupled electron transfer (PCET) from the n-doped SWCNT and ethanol. This work elucidates the mechanism behind the air-stability of n-type SWCNTs.

Clinical application of endoscopic soft palate augmentation in the treatment of velopharyngeal insufficiency.

Velopharyngeal structure augmentation with the injection of autologous fat tissue into the nasal mucosa of the soft palate has been reported previously. However, as the injection points in the velopharyngeal space cannot be observed directly, these injections may be difficult to perform accurately. This report describes a new endoscope-assisted approach in which the materials for velopharyngeal structure augmentation are administered while observing the injection points directly, also enabling adjustment of the amount of material injected. A case series of five patients aged 8-16 years who underwent endoscopic soft palate augmentation under general anaesthesia is reported. Autologous fat tissue was injected into the nasal mucosa of the soft palate using a needle-type device of an endoscope, and the effects of the treatment were evaluated. The injections were performed successfully, and the velopharyngeal function was improved. This new technique of endoscopy-assisted augmentation was useful for the treatment of velopharyngeal insufficiency.

Tratamiento anestésico mediante bloqueo del plexo braquial costoclavicular con analgesia controlada por el paciente en Pediatría: caso clínico / Anesthetic management using costoclavicular brachial plexus block with patient-controlled analgesia in Pediatrics: A case report

El bloqueo del plexo braquial costoclavicular (CBPB) ha venido recibiendo atención creciente como técnica eficaz en la cirugía de la parte superior del brazo realizada sin parálisis frénica. Sin embargo, se carece de estudios en niños. Se realizó CBPB a una niña de 10 años sometida a osteotomía radial y ulnar programada, debido a exostosis múltiples cartilaginosos y elongación ulnar. Se realizó CBPB con administración de un bolo de 10ml de levobupivacaína al 0,25%, sustituyéndose secuencialmente el catéter en el espacio costoclavicular derecho. Tras la cirugía, se inició infusión continua de 2ml/h de levobupivacaína al 0,17% a través de catéter, junto con analgesia controlada por el paciente (PCA) de 3ml de levobupivacaína al 0,17% con bloqueo de 60 min. La paciente se quejó de dolor de nivel 5/10 de la escala numérica (NRS) transcurridas 2h de la cirugía, que mejoró inmediatamente tras la administración del bolo. Por lo demás, la analgesia inducida por CBPB fue efectiva (NRS ≤ 2). El CBPB con PCA puede aportar una analgesia adecuada en casos pediátricos.(AU)

Anesthetic management using costoclavicular brachial plexus block with patient-controlled analgesia in pediatrics: a case report Abstract The costoclavicular brachial plexus block (CBPB) has been receiving increasing attention as an effective technique for upper arm surgery conducted without phrenic paralysis. However, studies in children are lacking. CBPB was applied to a 10 year-old girl undergoing scheduled radial and ulnar osteotomy due to multiple cartilaginous exostoses and ulnar lengthening. CBPB was performed with a bolo administration of 10 mL of 0.25% levobupivacaine, and the catheter was sequentially replaced in the right costoclavicular space. After surgery, a continuous infusion of 0.17% levobupivacaine through a catheter was initiated at 2 mL/h, along with patient-controlled analgesia (PCA) of 3 mL 0.17% levobupivacaine with a 60-minute lock out. The patient complained of 5/10 pain on the numerical rating scale (NRS) 2 hours after surgery, which improved immediately after bolus administration. The analgesia induced by CBPB was otherwise effective (NRS ≤ 2). CBPB with PCA may provide adequate analgesia in pediatric cases.(AU)

Anesthetic management using costoclavicular brachial plexus block with patient-controlled analgesia in Pediatrics: A case report.

The costoclavicular brachial plexus block (CBPB) has been receiving increasing attention as an effective technique for upper arm surgery conducted without phrenic paralysis. However, studies in children are lacking. CBPB was applied to a 10 year-old girl undergoing scheduled radial and ulnar osteotomy due to multiple cartilaginous exostoses and ulnar lengthening. CBPB was performed with a bolus administration of 10 mL of 0.25% levobupivacaine, and the catheter was sequentially replaced in the right costoclavicular space. After surgery, a continuous infusion of 0.17% levobupivacaine through a catheter was initiated at 2 mL/h, along with patient-controlled analgesia (PCA) of 3 mL 0.17% levobupivacaine with a 60-min lock out. The patient complained of 5/10 pain on the numerical rating scale (NRS) 2 h after surgery, which improved immediately after bolus administration. The analgesia induced by CBPB was otherwise effective (NRS ≤ 2). CBPB with PCA may provide adequate analgesia in paediatric cases.

Heavily T2-weighted imaging findings of spinal cord swelling in dogs with intervertebral disc extrusion.

ABSTRACT: This study investigated causes of attenuation of cerebrospinal fluid (CSF) signal on heavily T2-weighted (T2W) images in dogs with thoracolumbar disc extrusion. Medical records and magnetic resonance images were retrospectively reviewed. Dogs were classified into the following grades; grade 1, non-ambulatory paraparesis; grade 2, paraplegia with deep pain perception and grade 3, paraplegia without deep pain perception. The length of intramedullary T2W hyperintensity of the spinal cord, cranial/ caudal expansion of extradural compressive materials (ECM), and the CSF signal attenuation were measured. Ratios to the second lumbar vertebra (L2) were calculated for the length of intramedullary T2W hyperintensity (T2W:L2), cranial/caudal expansion of ECM (ECML:L2), and CSF signal attenuation (CSF:L2). The dogs were classified into focal or extended T2W hyperintensity groups according to the length [focal, shorter than length of L2; extended, longer than L2]. The area of EMC and the spinal canal were measured on transverse images at the lesion deriving occupancy ratio. The correlation between CSF:L2 and other data were analysed, and CSF:L2 was compared between the grades. In dogs with intramedullary T2W hyperintensity, the locations of CSF attenuation and the hyperintensity were compared if those locations were matched. Fifty-five dogs were included, 36 of which showed intramedullary T2W hyperintensity. Twenty-two of 36 dogs were considered as match of the location of the CSF attenuation and hyperintensity. CSF:L2 was significantly correlated with T2W:L2 in dogs with extended T2W hyperintensity (p = 0.0002), while CSF:L2 was significantly correlated with ECML:L2 in dogs with focal or no T2W hyperintensity (p = 0.0103 and p = 0.0364, respectively). CSF:L2 in grade 3 was significantly greater than those in patients who were grade 1 or 2 (both p < 0.001). In conclusion, higher CSF:L2, which was frequently seen in grade 3, would be most consistent with a higher T2W:L2 which might indicate spinal cord swelling.

Pedunculated colorectal polyps with heads ≤ 1 cm in diameter can be resected using cold snare polypectomy.

BACKGROUND AND STUDY AIMS: Cold snare polypectomy (CSP) is not recommended for the resection of pedunculated colorectal polyp. The aim of this study was to examine the adequacy of CSP compared to hot snare polypectomy (HSP) for the complete resection of pedunculated polyps with heads ≤ 1 cm in diameter. PATIENTS AND METHODS: This was a retrospective study of a cohort of consecutive outpatients who had resection of pedunculated polyps with heads 6-10 mm in diameter using either dedicated CSP or HSP from 2014 through 2019. The primary outcome measure was occurrence of delayed bleeding. Secondary outcome measures included total procedure time, en bloc resection rate, immediate bleeding, and number of clips used. RESULTS: 415 patients with 444 eligible polyps were enrolled; the CSP group (363 patients; 386 polyps) and HSP group (52 patients; 58 polyps). Patient characteristics, polyp characteristics and en bloc resection rate were similar between groups. The mean total procedure time and mean number (range) of hemostatic clips/ patient used were significantly lower with CSP than with HSP (18± 8 min vs. 25± 9 min, P<0.001; 1.1 ± 0.6 (1-3) vs.3.1 ± 1.6 (1-5), respectively, P<0.001). Delayed bleeding occurred significantly less frequently in the CSP, 0% (0/363 vs.3.8% (2/52) in the HSP group (P<0.001), although immediate bleeding was significantly higher in CSP than HSP (84% (325/386) vs. 12% (7/58), P<0.001). CONCLUSION: Pedunculated colorectal polyps with heads ≤ 1 cm can be removed using CSP, which has several advantages over HSP.

Anesthetic management using costoclavicular brachial plexus block with patient-controlled analgesia in Pediatrics: A case report. / Tratamiento anestésico mediante bloqueo del plexo braquial costoclavicular con analgesia controlada por el paciente en Pediatría: caso clínico.

Anesthetic management using costoclavicular brachial plexus block with patient-controlled analgesia in pediatrics: a case report Abstract The costoclavicular brachial plexus block (CBPB) has been receiving increasing attention as an effective technique for upper arm surgery conducted without phrenic paralysis. However, studies in children are lacking. CBPB was applied to a 10 year-old girl undergoing scheduled radial and ulnar osteotomy due to multiple cartilaginous exostoses and ulnar lengthening. CBPB was performed with a bolo administration of 10 mL of 0.25% levobupivacaine, and the catheter was sequentially replaced in the right costoclavicular space. After surgery, a continuous infusion of 0.17% levobupivacaine through a catheter was initiated at 2 mL/h, along with patient-controlled analgesia (PCA) of 3 mL 0.17% levobupivacaine with a 60-minute lock out. The patient complained of 5/10 pain on the numerical rating scale (NRS) 2 hours after surgery, which improved immediately after bolus administration. The analgesia induced by CBPB was otherwise effective (NRS ≤ 2). CBPB with PCA may provide adequate analgesia in pediatric cases.

In vitro evidence of propagation of superoxide dismutase-1 protein aggregation in canine degenerative myelopathy.

Canine degenerative myelopathy (DM) is a progressive and fatal neurodegenerative disorder that has been linked to mutations in the superoxide dismutase 1 (SOD1) gene. The accumulation of misfolded protein aggregates in spinal neurons and astrocytes is implicated as an important pathological process in DM; however, the mechanism of protein aggregate formation is largely unknown. In human neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), cell-to-cell propagation of disease-relevant proteins has been demonstrated. Therefore, in this study, propagation of aggregation-forming property of mutant SOD1 protein in DM in vitro was investigated. This study demonstrated that aggregates composed of canine wild type SOD1 protein were increased by co-transfection with canine mutant SOD1 (E40K SOD1), indicating intracellular propagation of SOD1 aggregates. Further, aggregated recombinant SOD1 proteins were released from the cells, taken up by other cells, and induced further aggregate formation of normally folded SOD1 proteins. These results suggest intercellular propagation of SOD1 aggregates. The hypothesis of cell-to-cell propagation of SOD1 aggregates proposed in this study may underly the progressive nature of DM pathology.

Floral and pollination characteristics of Eriocaulon heleocharioides, an extinct species in the wild, for evidence-based conservation management.

Generally, floral characteristics and pollination are important factors enhancing the quality and quantity of reproductive output for regeneration in plant conservation. However, lack of evidence-based management could decrease fitness under ex-situ conservation. We investigated the capitulum and pollination characteristics of Eriocaulon heleocharioides Satake (Eriocaulaceae), which is extinct in the wild, to develop an evidence-based conservation management plan incorporating previously ignored reproductive characteristics. To evaluate the functional characteristics of capitula, pollen-ovule ratio, and reproductive status (maximum pollination success/florivory damage) were investigated along six flowering sequences of capitulum. To evaluate the effect of plant density on pollen transfer, high- and low-density plots were established. Total deposited pollen on stigma, insect visitation, and visit duration per capitulum were observed. A significantly lower pollen-ovule ratio was observed in the first of six capitula, reflecting higher female functionality. The highest pollination success was found in the second-fourth capitula, whereas florivory increased along the terminal capitula position. High plant density affected the pollen deposited on stigmas via insect visitation and low pollinator visit duration. Different capitula in E. heleocharioides could have different effects: different sexual functionality, enhancement of reproductive output both in quality and quantity through active pollen transfer, and escaping from florivores. High plant density could facilitate outcross-pollen transfer in E. heleocharioides. Multiple perspectives are important for determining potential reproductive success in ex-situ conservation. Thus, density management reflecting capitulum characteristics could improve the efficiency of conservation efforts for E. heleocharioides.

Chest complications in immunocompromised patients without acquired immunodeficiency syndrome (AIDS): differentiation between infectious and non-infectious diseases using high-resolution CT findings.

AIM: To differentiate between infectious and non-infectious diseases occurring in immunocompromised patients without acquired immunodeficiency syndrome (AIDS) using high-resolution computed tomography (HRCT). MATERIALS AND METHODS: HRCT images of 555 patients with chest complications were reviewed retrospectively. Infectious diseases (n=341) included bacterial pneumonia (n=123), fungal infection (n=80), septic emboli (n=11), tuberculosis (n=15), pneumocystis pneumonia (n=101), and cytomegalovirus pneumonia (n=11), while non-infectious diseases (n=214) included drug toxicity (n=84), infiltration of underlying diseases (n=83), idiopathic pneumonia syndrome (n=34), diffuse alveolar haemorrhage (n=8), and pulmonary oedema (n=5). Lung parenchymal abnormalities were compared between the two groups using the χ2 test and multiple logistic regression analysis. RESULTS: The χ2 test results showed significant differences in many HRCT findings between the two groups. Multiple logistic regression analysis results indicated the presence of nodules with a halo and the absence of interlobular septal (ILS) thickening were the significant indicators that could differentiate infectious from non-infectious diseases. ILS thickening was generally less frequent among most infectious diseases and more frequent among most non-infectious diseases, with a good odds ratio (7.887, p<0.001). The sensitivity and accuracy for infectious diseases in the absence of ILS thickening were better (70% and 73%, respectively) than those of nodules with a halo (19% and 48%, respectively), while the specificity in the nodules with a halo was better (93%) than that of ILS thickening (78%). CONCLUSIONS: The presence of nodules with a halo or the absence of ILS thickening tends to suggest infectious disease. Specifically, ILS thickening seems to be a more reliable indicator.

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.

Whole-Genome Sequencing of the NARO World Rice Core Collection (WRC) as the Basis for Diversity and Association Studies.

Genebanks provide access to diverse materials for crop improvement. To utilize and evaluate them effectively, core collections, such as the World Rice Core Collection (WRC) in the Genebank at the National Agriculture and Food Research Organization, have been developed. Because the WRC consists of 69 accessions with a high degree of genetic diversity, it has been used for >300 projects. To allow deeper investigation of existing WRC data and to further promote research using Genebank rice accessions, we performed whole-genome resequencing of these 69 accessions, examining their sequence variation by mapping against the Oryza sativa ssp. japonica Nipponbare genome. We obtained a total of 2,805,329 single nucleotide polymorphisms (SNPs) and 357,639 insertion-deletions. Based on the principal component analysis and population structure analysis of these data, the WRC can be classified into three major groups. We applied TASUKE, a multiple genome browser to visualize the different WRC genome sequences, and classified haplotype groups of genes affecting seed characteristics and heading date. TASUKE thus provides access to WRC genotypes as a tool for reverse genetics. We examined the suitability of the compact WRC population for genome-wide association studies (GWASs). Heading date, affected by a large number of quantitative trait loci (QTLs), was not associated with known genes, but several seed-related phenotypes were associated with known genes. Thus, for QTLs of strong effect, the compact WRC performed well in GWAS. This information enables us to understand genetic diversity in 37,000 rice accessions maintained in the Genebank and to find genes associated with different phenotypes. The sequence data have been deposited in DNA Data Bank of Japan Sequence Read Archive (DRA) (Supplementary Table S1).

Randomized clinical trial of extensive intraoperative peritoneal lavage versus standard treatment for resectable advanced gastric cancer (CCOG 1102 trial).

BACKGROUND: A survival benefit of extensive intraoperative peritoneal lavage (EIPL) has been reported in patients with gastric cancer with positive peritoneal cytology. The hypothesis of this study was that EIPL may reduce peritoneal recurrence in patients with advanced gastric cancer who undergo surgery with curative intent. METHODS: This was an open-label, multi-institutional, randomized, phase 3 trial to assess the effects of EIPL versus standard treatment after curative gastrectomy for resectable gastric cancer of T3 status or above. The primary endpoint was disease-free survival (DFS); secondary endpoints were overall survival, peritoneal recurrence-free survival and incidence of adverse events. RESULTS: Between July 2011 and January 2014, 314 patients were enrolled from 15 institutions and 295 patients were analysed (145 and 150 in the EIPL and no-EIPL groups respectively). The 3-year DFS rate was 63·9 (95 per cent c.i. 55·5 to 71·2) per cent in the EIPL group and 59·7 (51·3 to 67·1) per cent in the control group (hazard ratio (HR) 0·81, 95 per cent c.i. 0·57 to 1·16; P = 0·249). The 3-year overall survival rate was 75·0 (67·1 to 81·3) per cent in the EIPL group and 73·7 (65·9 to 80·1) per cent in the control group (HR 0·91, 0·60 to 1·37; P = 0·634). Peritoneal recurrence-free survival was not significantly different between the two groups (HR 0·92, 0·62 to 1·36; P = 0·676). No intraoperative complications related to EIPL were observed. CONCLUSION: EIPL did not improve survival or peritoneal recurrence in patients who underwent gastrectomy for advanced gastric cancer. Registration number: 000005907 (http://www.umin.ac.jp/ctr/index.htm).

ANTECEDENTES: Se ha descrito que un lavado peritoneal extenso intraoperatorio (extensive intraoperative peritoneal lavage, EIPL) proporciona un beneficio en la supervivencia en pacientes con cáncer gástrico con citología peritoneal positiva. La hipótesis de este estudio era que el EIPL podría disminuir la recidiva peritoneal en pacientes con cáncer gástrico avanzado sometidos a cirugía con intención curativa. MÉTODOS: Ensayo clínico fase 3, abierto, multicéntrico y aleatorizado para evaluar los efectos de un lavado peritoneal extenso intraoperatorio (EIPL) frente a tratamiento estándar tras gastrectomía curativa por cáncer gástrico ≥T3 resecable. La variable de resultado primaria fue la supervivencia libre de enfermedad (disease-free survival, DFS), y las variables de resultado secundarias fueron la supervivencia global (overall survival, OS), la supervivencia libre de recidiva peritoneal y la incidencia de efectos adversos. RESULTADOS: Entre julio de 2011 y enero de 2014, se reclutaron 314 pacientes de 15 instituciones y se analizaron los datos de 295 pacientes (145 en el grupo con EIPL y 150 en el grupo sin EIPL). La DFS a los 3 años fue 63,9% (i.c. del 95% 55,5-71,2) en el grupo con EIPL y 59,7% (i.c. del 95% 51,3-67,1) en el grupo control (cociente de riesgos instantáneos, hazard ratio, HR 0,81 (i.c. del 95% 0,57-1,16), P = 0,249). La OS a los 3 años fue 75,0% (i.c. del 95% 67,1-81,3) en el grupo con EIPL y 73,7% (i.c. del 95% 65,9-80,1) en el grupo control (HR 0,91 i.c. del 95% 0,60-1,37), P = 0,634). No se observaron diferencias estadísticamente significativas entre los dos grupos en la supervivencia libre de recidiva peritoneal (P = 0,676, HR 0,92 (i.c. del 95% 0,62-1,36). No se observaron complicaciones intraoperatorias relacionadas con EIPL. CONCLUSIÓN: El EIPL no mejoró la supervivencia o la recidiva peritoneal en pacientes sometidos a gastrectomía por cáncer gástrico avanzado.

Delayed lupus nephritis in the course of systemic lupus erythematosus is associated with a poorer treatment response: a multicentre, retrospective cohort study in Japan.

OBJECTIVE: The objective of this study was to investigate possible differences in treatment responses between two categories for the onset of lupus nephritis. METHODS: We performed a multicentre, retrospective cohort study of class III-V lupus nephritis patients diagnosed between 1997 and 2014. The renal responses to initial induction therapy were compared between patients who developed lupus nephritis within one year from diagnosis of systemic lupus erythematosus (early (E-) LN) and the remainder (delayed (D-) LN) using the Kaplan-Meier method. We determined the predictors of renal response as well as renal flares and long-term renal outcomes using multivariate Cox regression analyses. RESULTS: A total of 107 E-LN and 70 D-LN patients were followed up for a median of 10.2 years. Log-rank tests showed a lower cumulative incidence of complete response in D-LN compared with E-LN patients. Multivariate analysis identified D-LN (hazard ratio (HR) 0.48, 95% confidence interval (CI) 0.33-0.70), nephrotic syndrome at baseline, and a chronicity index greater than 2 as negative predictors of complete response. D-LN patients were more likely to experience renal flares. D-LN (HR 2.54, 95% CI 1.10-5.83) and decreased renal function were significant predictors of chronic kidney disease at baseline. CONCLUSION: D-LN was a predictor of poorer treatment outcomes, in addition to renal histology and severity of nephritis at lupus nephritis onset.

Immunogenomic profiles associated with response to neoadjuvant chemoradiotherapy in patients with rectal cancer.

BACKGROUND: Accumulating evidence suggests that radiotherapy success has an immune-associated component. The immunogenomic profiles associated with responses to chemoradiotherapy (CRT) were assessed in patients with locally advanced rectal cancer in this study. METHODS: CD8+ tumour-infiltrating lymphocyte (TIL) and stromal lymphocyte densities were assessed by immunohistochemistry using pretreatment biopsies from patients with advanced rectal cancer who had preoperative CRT. Whole-exome sequencing and gene expression microarray analysis were conducted to investigate the genomic properties associated with the response to CRT and CD8+ TIL density. Response to CRT was determined based on Dworak tumour regression grade (TRG); tumours with complete (TRG 4) or near-complete (TRG 3) regression were grouped as good responders, and those with TRG 1 as non-responders. RESULTS: Immunohistochemical examinations (275 patients) showed that pre-CRT CD8+ TIL density was associated with better response to CRT and improved recurrence-free survival, whereas pre-CRT stromal CD8+ cell density was not associated with either response to CRT or recurrence-free survival. Whole-exome sequencing (74 patients) showed that the numbers of single-nucleotide variations (SNVs) and neoantigens predicted from SNVs were higher in good responders than in non-responders, and these correlated positively with CD8+ TIL density (rS = 0·315 and rS = 0·334 respectively). Gene expression microarray (90 patients) showed that CD8A expression correlated positively with the expression of programmed cell death 1 (PDCD1) (rS = 0·264) and lymphocyte-activation gene 3 (LAG3) (rS = 0·507). CONCLUSION: Pre-CRT neoantigen-specific CD8+ T cell priming may be a key event in CRT responses where immune checkpoint molecules could be useful targets to enhance tumour regression.

ANTECEDENTES: Las evidencias existentes sugieren que el éxito de la radioterapia tiene un componente asociado con el sistema inmunitario. En este estudio se evaluaron los perfiles inmunogenómicos asociados con la respuesta a la quimiorradioterapia (chemoradiotherapy, CRT) en pacientes con cáncer de recto localmente avanzado. MÉTODOS: Las densidades de los linfocitos infiltrantes de tumor CD8+ (tumour-infiltrating lymphocyte, TIL) y de los linfocitos del estroma se evaluaron por inmunohistoquímicas en las biopsias antes del tratamiento de pacientes con cáncer de recto localmente avanzado que recibieron CRT preoperatoria. Se realizó secuenciación de todo el exoma, así como microarrays de expresión génica, para investigar las propiedades genómicas asociadas con la respuesta a la CRT y a la densidad de los TIL CD8+. La respuesta a la CRT se determinó según el grado de regresión del tumor de Dworak (tumour regression grade, TRG), agrupándose como buenos respondedores los casos de regresión tumoral completa (TRG4) o casi completa (TRG3) y como no respondedores, los casos de grado TRG1. RESULTADOS: Los exámenes inmunohistoquímicos (n = 275) mostraron que la densidad pre-CRT de TIL CD8+ se asoció con una mejor respuesta a la CRT y una mejor supervivencia libre de recidiva, aunque la densidad de células CD8+ del estroma previa a la CRT no se asoció con la respuesta a la CRT ni con la supervivencia libre de recidiva. La secuenciación de todo el exoma (n = 74) mostró que el número de variaciones de nucleótidos únicos (single nucleotide variations, SNVs) y los neoantígenos predichos a partir de los SNVs fueron mayores en los que respondieron bien que en los que no respondieron, y éstos se correlacionaron positivamente con la densidad de los TIL CD8+ (Spearman r = 0,315 y r = 0,334 respectivamente). Los microarrays de expresión génica (n = 90) mostraron que la expresión CD8A se correlacionó positivamente con la expresión del ligando de muerte programada-1 (r = 0,264) y con el antígeno linfocitario del gen 3 (r = 0,507). CONCLUSIÓN: La activación de células T CD8+ específicas para neoantígenos previa a la CRT puede ser un evento clave en la respuesta a la misma donde las moléculas del punto de control inmunitario podrían ser dianas útiles para intensificar la regresión del tumor.

Salvage surgery for a locally persistent or recurrent tumour in maxillary cancer patients who have undergone radiotherapy and concomitant intra-arterial cisplatin: implications for surgical margin assessment.

Limited information about salvage surgery is available for locally persistent and recurrent maxillary sinus cancers after the completion of chemoradiation therapy. Seventy-six maxillary sinus cancer patients who had undergone chemoradioselection using initial radiotherapy and concomitant intra-arterial cisplatin were screened retrospectively. Twenty-four of these patients who had a locally persistent or recurrent tumour were investigated. The 2-year overall survival rate of patients with maxillary sinus cancer of all types was 39.0% for those who underwent salvage surgery and 10.0% for those who did not. The 2-year overall survival rate of patients with maxillary sinus squamous cell carcinoma was 45.8% for those who underwent salvage surgery and 11.1% for those who did not. Furthermore, the 2-year local control and overall survival rates of patients with positive and negative surgical margins were 14.3% and 83.3% and 14.3% and 66.7%, respectively. There were significant differences in local control (P=0.004) and overall survival (P=0.005) regarding surgical margin status. Although salvage surgery for a locally persistent or recurrent maxillary sinus cancer is a feasible treatment, patients with positive surgical margins are more prone to local relapse. Therefore, surgical safety margins should be assessed thoroughly.

HRCT findings of collagen vascular disease-related interstitial pneumonia (CVD-IP): a comparative study among individual underlying diseases.

AIM: To identify characteristic high-resolution computed tomography (CT) findings for individual collagen vascular disease (CVD)-related interstitial pneumonias (IPs). MATERIALS AND METHODS: The HRCT findings of 187 patients with CVD, including 55 patients with rheumatoid arthritis (RA), 50 with systemic sclerosis (SSc), 46 with polymyositis/dermatomyositis (PM/DM), 15 with mixed connective tissue disease, 11 with primary Sjögren's syndrome, and 10 with systemic lupus erythematosus, were evaluated. Lung parenchymal abnormalities were compared among CVDs using χ2 test, Kruskal-Wallis test, and multiple logistic regression analysis. A CT-pathology correlation was performed in 23 patients. RESULTS: In RA-IP, honeycombing was identified as the significant indicator based on multiple logistic regression analyses. Traction bronchiectasis (81.8%) was further identified as the most frequent finding based on χ2 test. In SSc IP, lymph node enlargement and oesophageal dilatation were identified as the indicators based on multiple logistic regression analyses, and ground-glass opacity (GGO) was the most extensive based on Kruskal-Wallis test, which reflects the higher frequency of the pathological nonspecific interstitial pneumonia (NSIP) pattern present in the CT-pathology correlation. In PM/DM IP, airspace consolidation and the absence of honeycombing were identified as the indicators based on multiple logistic regression analyses, and predominance of consolidation over GGO (32.6%) and predominant subpleural distribution of GGO/consolidation (41.3%) were further identified as the most frequent findings based on χ2 test, which reflects the higher frequency of the pathological NSIP and/or the organising pneumonia patterns present in the CT-pathology correlation. CONCLUSION: Several characteristic high-resolution CT findings with utility for estimating underlying CVD were identified.