Is Prior Nonoperative or Operative Treatment of Dysplasia of the Hip Associated With Poorer Results of Periacetabular Osteotomy?

BACKGROUND: Understanding the implications of either nonoperative or operative treatment of developmental dysplasia of the hip (DDH) performed before periacetabular osteotomy (PAO) is critical to counseling patients and their families. There are limited studies, however, on PAO for the treatment of residual DDH after surgical intervention during childhood, and even less information about PAO after prior nonoperative treatment. QUESTIONS/PURPOSES: We analyzed patients who had undergone PAO for DDH and asked: Did patients with prior childhood treatment (either operative or nonoperative) (1) improve less in modified Harris hip score (mHHS), 12-item International Hip Outcome Tool (iHOT-12) score, or WOMAC score; (2) demonstrate more severe preoperative deformities; and (3) receive less complete radiographic correction and have more frequent complications than did patients whose hips had not undergone prior treatment? We also asked: (4) Were there subgroup differences among patients with DDH treated nonoperatively versus operatively before PAO in these same functional and radiographic parameters? METHODS: Between January 2011 and December 2020, a total of 90 PAOs were performed in 82 patients who had prior surgical or nonsurgical treatment. Of those, 3 patients (3 hips) with neuromuscular diseases were excluded, 4 patients (5 hips) were excluded for having received treatment after childhood, 7 hips that had undergone bilateral PAOs were excluded, and another 4 patients (4 hips) were lost to follow-up before the minimum study period of 2 years, leaving 71 patients (71 hips) for analysis (the previous treatment group). Among these, 32 patients had a history of previous surgery (the previous surgery group), and 39 patients had prior nonsurgical treatment (such as a Pavlik harness, closed reduction, spica casting) (the previous nonoperative group). During the same period, 1109 PAOs were performed in 956 patients who had no history of previous hip treatment. Following a 1:2 ratio, 142 patients (142 hips) were selected as the control group by matching for age (within 2 years difference), year of surgery (same year), and follow-up time (within 1-year difference). The patient characteristics for both the previous treatment group and the control group exhibited comparability, with mean ± SD follow-up durations of 49 ± 23 months and 48 ± 19 months, respectively. Within the previous 5 years, 3 patients (8%) in the previous nonoperative group, 4 patients (13%) in the previous surgery group, and 15 patients (11%) in the control group had not attended follow-up visits. We compared hip function and radiographic results between the two groups and performed a subgroup analysis between the previous surgery group and the previous nonoperative group. Hip function was assessed using the mHHS questionnaire, the WOMAC, and the iHOT-12 with attention to the minimum clinically important differences of these tools. The threshold values for clinically important improvement were 9.6 points, 13 points, and 16.1 points for the mHHS, iHOT-12, and WOMAC, respectively. Radiographic measurements included the lateral center-edge angle (LCEA), anterior center-edge angle (ACEA), Tönnis angle, acetabulum-head index, and acetabular wall index. We also evaluated Tönnis osteoarthritis grade and femoral head deformity. Occurrences of adverse radiographic events such as posterior column fracture, nonunion, stress fractures, insufficient coverage or overcoverage, acetabular protrusion, and progression of osteoarthritis were recorded. RESULTS: We found no clinically important differences in magnitude of improvement between the previous treatment group and the control group in terms of mHHS (mean ± SD 10 ± 12 versus 12 ± 12; p = 0.36), iHOT-12 (25 ± 18 versus 26 ± 19; p = 0.51), or WOMAC score (12 ± 12 versus 15 ± 19; p = 0.17). Preoperative deformity in the previous treatment group was more severe than in the control group (mean ± SD LCEA -1° ± 9° versus 5° ± 8°; ACEA -8° ± 18° versus 1° ± 14°; Tönnis angle 31° ± 7° versus 27° ± 7°; acetabulum-head index 56% ± 13% versus 61% ± 8%; all p < 0.001). In the previous treatment group, a higher percentage of patients exhibited flattening or irregularity of the femoral head compared with the control group (52% versus 9%; p < 0.001), and there was also a higher proportion of patients with Tönnis grade 1 or above (51% versus 42%; p < 0.001). Although there were still differences in LCEA, ACEA, and Tönnis angle between the two groups at the last follow-up, the differences were small, and the mean values were within the normal range. The previous treatment group had a higher risk of intraoperative posterior column fracture (14% and 5%; p = 0.02), insufficient acetabular coverage (20% and 8%; p = 0.01), and progression of osteoarthritis (17% and 8%; p = 0.04) compared with the control group. Subgroup analysis revealed no clinically important differences in magnitude of improvement between the previous surgery group and the previous nonoperative group in terms of mHHS (10 ± 14 versus 10 ± 11; p = 0.91), iHOT-12 (22 ± 21 versus 27 ± 14; p = 0.26), or WOMAC score (12 ± 14 versus 12 ± 11; p = 0.94). Apart from a higher proportion of patients who presented with arthritis (72% versus 34%; p = 0.01) and a smaller anterior wall index (11% ± 11% versus 20% ± 12%; p = 0.01) in the previous surgery group, all other preoperative radiographic parameters were consistent between the two groups. Additionally, the previous surgery group had a higher frequency of arthritis progression (28% versus 8%; p = 0.02), while the frequencies of other complications were similar between the two groups. Specifically, the frequencies of pubic ramus nonunion (22% versus 21%; p = 0.89), intraoperative posterior column fracture (19% versus 10%; p = 0.50), and insufficient acetabular coverage (25% versus 15%; p = 0.31) were high in both groups. CONCLUSION: We found no clinically important difference in the magnitude of improvement between patients who had childhood treatment and those who did not, but patients who had prior childhood treatment were more likely to experience serious complications, and radiographic correction in those patients was less complete. As in the case of patients who have had prior operative treatments, it is crucial not to overlook the unexpectedly severe deformity of residual DDH after previous nonoperative treatment and complications following PAO. Surgeons and patients alike should be aware of the potential for worse radiographic outcomes or an increased risk of complications when prior operative or nonoperative treatment has preceded PAO. Future studies might investigate optimal management strategies for this specific group of patients to improve outcomes and reduce complications. LEVEL OF EVIDENCE: Level III, therapeutic study.

A novel fluorescent dye selectively images and kills cancer stem cells by targeting mitochondria: Evidence from a cell line­based zebrafish xenograft model.

Numerous agents such as near-infrared dyes that are characterized by specialized cancer imaging and cytotoxicity effects have key roles in cancer diagnosis and therapy via molecularly targeting special biological tissues, organelles and processes. In the present study, a novel fluorescent compound was demonstrated to inhibit cancer cell proliferation in a zebrafish model with slight in vivo toxicity. Further studies demonstrated selective staining of cancer cells and even putative cancer stem cells via accumulation of the dye in the mitochondria of cancer cells, compared with normal cells. Moreover, this compound was also used to image cancer cells in vivo using a zebrafish model. The compound displayed no apparent toxicity to the host animal. Overall, the data indicated that this compound was worthy of further evaluation due to its low toxicity and selective cancer cell imaging and killing effects. It could be a useful tool in cancer research.

Astrocytes promote the proliferation of oligodendrocyte precursor cells through connexin 47-mediated LAMB2 secretion in exosomes.

BACKGROUND: Oligodendrocyte precursor cells (OPCs) can proliferate and differentiate into oligodendrocytes, the only myelin-forming cells in the central nervous system. Proliferating OPCs promotes remyelination in neurodegenerative diseases. Astrocytes (ASTs) are the most widespread cells in the brain and play a beneficial role in the proliferation of OPCs. Connexin 47 (Cx47) is the main component of AST-OPC gap junctions to regulate OPC proliferation. Nonetheless, the specific mechanism remains unclear. METHODS AND RESULTS: This study investigates the proliferation mechanism of OPCs connected to ASTs via Cx47. Cx47 siRNA significantly inhibited OPCs from entering the proliferation cycle. Transcriptome sequencing of OPCs and gene ontology enrichment analysis revealed that ASTs enhanced the exosome secretion by OPCs via Cx47. Transmission electron microscopy, Western blot, and nanoparticle tracking analysis indicated that the OPC proliferation was related to extracellular exosomes. Cx47 siRNA decreased the OPC proliferation and exosome secretion in AST-OPC cocultures. Exogenous exosome supplementation alleviated the inhibitory effect of Cx47 siRNA and significantly improved OPC proliferation. Mass spectrometry revealed that LAMB2 was abundant in exosomes. The administration of exogenous LAMB2 induced DNA replication in the S phase in OPCs by activating cyclin D1. CONCLUSIONS: Collectively, ASTs induce the secretion of exosomes that carry LAMB2 by OPCs via Cx47 to upregulate cyclin D1 thereby accelerating OPC proliferation.

A Review of Novel Cardiac Biomarkers in Acute or Chronic Cardiovascular Diseases: The Role of Soluble ST2 (sST2), Lipoprotein-Associated Phospholipase A2 (Lp-PLA2), Myeloperoxidase (MPO), and Procalcitonin (PCT).

While the received traditional predictors are still the mainstay in the diagnosis and prognosis of CVD events, increasing studies have focused on exploring the ancillary effect of biomarkers for the aspiring of precision. Under which circumstances, soluble ST2 (sST2), lipoprotein-associated phospholipase A2 (Lp-PLA2), myeloperoxidase (MPO), and procalcitonin (PCT) have recently emerged as promising markers in the field of both acute and chronic cardiovascular diseases. Existent clinical studies have demonstrated the significant associations between these markers with various CVD outcomes, which further verified the potentiality of markers in helping risk stratification and diagnostic and therapeutic work-up of patients. The current review article is aimed at illuminating the applicability of these four novels and often neglected cardiac biomarkers in common clinical scenarios, including acute myocardial infarction, acute heart failure, and chronic heart failure, especially in the emergency department. By thorough classification, combination, and discussion of biomarkers with clinical and instrumental evaluation, we hope the current study can provide insights into biomarkers and draw more attention to their importance.

Cigarette smoking and all-cause mortality in rural Chinese male adults: 15-year follow-up of the Anqing cohort study.

BACKGROUND: According to the Global Burden of Disease Study 2017, smoking is one of the leading four risk factors contributing to deaths in China. We aimed to evaluate the associations of smoking with all-cause mortality in a Chinese rural population. METHODS: Male participants over age 45 (n = 5367) from a large familial aggregation study in rural China, were included in the current analyses. A total of 528 former smokers and 3849 current smokers accounted for 10 and 71.7% of the cohort, respectively. Generalized Estimating Equations were used to evaluate the association between baseline smoking status and mortality, adjusting for pertinent covariates. RESULTS: There were 579 recorded deaths during the 15-year follow-up. Current smokers (odds ratio [OR],1.60; 95% CI,1.23-2.08) had higher all-cause mortality risks than nonsmokers. Relative to nonsmokers, current smokers of more than 40 pack-years ([OR],1.85; 95% CI,1.33-2.56) had a higher all-cause mortality risk. Compared to nonsmokers, current smokers who started smoking before age 20 ([OR],1.91; 95% CI,1.43-2.54) had a higher all-cause mortality risk, and former smokers in the lower pack-year group who quit after age 41 (median) ([OR],3.19; 95% CI,1.83-5.56) also had a higher risk of death after adjustment. Furthermore, former smokers who were also former drinkers had the highest significant risk of mortality than never smokers or drinkers. (P for interaction = 0.034). CONCLUSIONS: This study provides evidence that current smokers and former smokers have a higher mortality risk than nonsmokers and would benefit from cessation at a younger age.

Contrasting effects of iron reduction on thionation of diphenylarsinic acid in a biostimulated Acrisol.

Diphenylarsinic acid (DPAA) is an emerging phenylarsenic compound derived from chemical warfare agents. It has been suggested that biostimulation of sulfate reduction decreases the concentrations of DPAA in soils. However, biostimulation often induces Fe(III) reduction which may affect the mobility and thereby the transformation of DPAA. Here, a soil incubation experiment was carried out to elucidate the impact of Fe(III) reduction on the mobilization and transformation of DPAA in a biostimulated Acrisol with the addition of sulfate and lactate. DPAA was significantly mobilized and then thionated in the sulfide soil (amended with sulfate and sodium lactate) compared with the anoxic soil (without addition of sulfate or sodium lactate). At the start of the incubation period, 41.8% of the total DPAA in sulfide soil was mobilized, likely by the addition of sodium lactate, and DPAA was then almost completely released into the solution after 2 weeks of incubation, likely due to Fe(III) reduction. The relatively low fraction of oxalate-extractable Fe in Acrisol, which contributes significantly to DPAA sorption and is more active and reduction-susceptible, may explain the observation that only < 40% of the Fe(III) (hydr)oxides were reduced when DPAA was completely released into the solution. A more rapid and final enhanced elimination of DPAA was observed in sulfide soil and the fraction of total DPAA decreased to 60.1 and 91.0%, respectively, at the end of the incubation in sulfide soil and anoxic soil. The difference appears to result from increased DPAA mobilization and sulfate reduction in sulfide soil. On the other hand, the formation of FeS precipitate, a product of Fe and sulfate reduction, may reduce the efficiency of DPAA thionation. Accordingly, the potentially contrasting effects of Fe(III) reduction on DPAA thionation need be considered when planning biostimulated sulfate reduction strategies for DPAA-contaminated soils.