NOTCH4 potentiates the IL-13 induced genetic program in M2 alternative macrophages through the AP1 and IRF4-JMJD3 axis.

IL-13 signaling polarizes macrophages to an M2 alternatively activated phenotype, which regulates tissue repair and anti-inflammatory responses. However, an excessive activation of this pathway leads to severe pathologies, such as allergic airway inflammation and asthma. In this work, we identified NOTCH4 receptor as an important modulator of M2 macrophage activation. We show that the expression of NOTCH4 is induced by IL-13, mediated by Janus kinases and AP1 activity, probably mediated by the IL-13Rα1 and IL-13Rα2 signaling pathway. Furthermore, we demonstrate an important role for NOTCH4 signaling in the IL-13 induced gene expression program in macrophages, including various genes that contribute to pathogenesis of the airways in asthma, such as ARG1, YM1, CCL24, IL-10, or CD-163. We also demonstrate that NOTCH4 signaling modulates IL-13-induced gene expression by increasing IRF4 activity, mediated, at least in part, by the expression of the histone H3K27me3 demethylase JMJD3, and by increasing AP1-dependent transcription. In summary, our results provide evidence for an important role of NOTCH4 signaling in alternative activation of macrophages by IL-13 and suggest that NOTCH4 may contribute to the increased severity of lesions in M2 inflammatory responses, such as allergic asthma, which points to NOTCH4 as a potential new target for the treatment of these pathologies.

Single base-pair resolution analysis of DNA binding motif with MoMotif reveals an oncogenic function of CTCF zinc-finger 1 mutation.

Defining the impact of missense mutations on the recognition of DNA motifs is highly dependent on bioinformatic tools that define DNA binding elements. However, classical motif analysis tools remain limited in their capacity to identify subtle changes in complex binding motifs between distinct conditions. To overcome this limitation, we developed a new tool, MoMotif, that facilitates a sensitive identification, at the single base-pair resolution, of complex, or subtle, alterations to core binding motifs, discerned from ChIP-seq data. We employed MoMotif to define the previously uncharacterized recognition motif of CTCF zinc-finger 1 (ZF1), and to further define the impact of CTCF ZF1 mutation on its association with chromatin. Mutations of CTCF ZF1 are exclusive to breast cancer and are associated with metastasis and therapeutic resistance, but the underlying mechanisms are unclear. Using MoMotif, we identified an extension of the CTCF core binding motif, necessitating a functional ZF1 to bind appropriately. Using a combination of ChIP-Seq and RNA-Seq, we discover that the inability to bind this extended motif drives an altered transcriptional program associated with the oncogenic phenotypes observed clinically. Our study demonstrates that MoMotif is a powerful new tool for comparative ChIP-seq analysis and characterising DNA-protein contacts.

No Differences in Clinical Outcomes Between Hip Arthroscopy With Versus Without Capsular Closure in Patients With Cam- or Mixed-Type Femoroacetabular Impingement: A Randomized Controlled Trial.

PURPOSE: To compare 2-year clinical outcomes of primary hip arthroscopy with versus without capsular closure after interportal capsulotomy in patients with cam- or mixed-type femoroacetabular impingement (FAI). METHODS: Patients with cam- or mixed-type FAI undergoing primary hip arthroscopy with interportal capsulotomy were prospectively enrolled in this randomized controlled trial (RCT) and allocated into either capsular closure or no capsular closure groups. Patients were blinded to group allocation. Clinical outcomes were assessed preoperatively and at 2-year follow-up using the 12-item International Hip Outcome Tool (iHOT-12), modified Harris Hip Score (mHHS), and 6 subsections of the Copenhagen Hip and Groin Outcome Score (HAGOS). Complications and reoperations were noted. RESULTS: Eighty-four patients (100 hips) were enrolled, 49 hips in the capsular closure group and 51 in the no capsular closure group, with no significant differences in age (28.5 ± 7.5 vs 30.4 ± 8.4, P = .261), body mass index (23.5 ± 3.0 vs 23.4 ± 1.9, P = .665), and sex distribution (female: 10.2% vs 13.7%, P = .760). Four patients were lost to follow-up (2.0% vs 5.9%, P = .618) and 6 had reoperations (6.1% vs 5.9%, P = 1.000), which left 45 hips per group for clinical assessment. There were no significant differences between groups in the net change of iHOT-12 (28.3 ± 19.6 vs 32.5 ± 22.7, P = .388), mHHS (7.6 ± 13.1 vs 7.5 ± 10.2, P = .954), and subsections of HAGOS (P > .05). Complication rates were also similar between groups (P > .05). CONCLUSIONS: The present RCT compared primary hip arthroscopy with versus without capsular closure after interportal capsulotomy in a male-dominated, non-dysplastic, non-arthritic cohort with cam- or mixed-type FAI and found no significant differences in patient-reported clinical outcomes, complication rates, or reoperation rates. LEVEL OF EVIDENCE: Level I, randomized controlled trial.

Satisfactory mid-term clinical outcomes of endoscopic tenotomy for iliopsoas tendinopathy following total hip arthroplasty.

PURPOSE: To report 5-year outcomes of endoscopic iliopsoas tenotomy in patients with iliopsoas tendinopathy following total hip arthroplasty (THA) and determine whether clinical scores are associated with cup position. METHODS: Patients who underwent endoscopic iliopsoas tenotomy for iliopsoas tendinopathy following THA (2014-2017) were contacted. Indications for endoscopic iliopsoas tenotomy after THA were groin pain during active hip flexion, exclusion of other causes of groin pain, and no pain relief after 6 months of conservative treatment. Pretenotomy cup inclination and anteversion were measured on radiographs; axial and sagittal cup overhang were measured on computed tomography (CT) scans. Oxford hip score (OHS), modified Harris hip score (mHHS), and groin pain were assessed. RESULTS: The initial cohort comprised 16 men (17 hips) and 31 women (32 hips), aged 60.7 ± 10.6 years. Cup inclination and anteversion were, respectively, 46.2 ± 6.2° and 14.6 ± 8.4°, while axial and sagittal cup overhang were, respectively, 4.4 ± 4.0 mm and 6.9 ± 4.5 mm. At ≥5 years follow-up, four hips underwent cup and stem revision, two underwent isolated cup revision and one underwent secondary iliopsoas tenotomy. OHS improved by 23 ± 10 and mHHS improved by 31 ± 16. Posttenotomy groin pain was slight in 20.0%, mild in 17.5% and moderate in 12.5%. Regression analyses revealed that net change in mHHS decreased with sagittal cup overhang (ß = -3.1; 95% confidence interval [CI] = -4.6 to -1.7; p < 0.001), but that there were no associations between cup position and net change in OHS. CONCLUSIONS: Endoscopic iliopsoas tenotomy provides good mid-term clinical outcomes in patients with iliopsoas tendinopathy following THA. Furthermore, improvements in mHHS were found to decrease with increasing sagittal cup overhang, in cases for which adequate preoperative imaging was available. LEVEL OF EVIDENCE: Level IV.

Acute Chagas disease associated with ingestion of contaminated food in Brazilian western Amazon.

OBJECTIVE: To describe clinical, epidemiological and management information on cases of acute Chagas disease (ACD) by oral transmission in the state of Amazonas in western Amazon. METHODS: Manual and electronic medical records of patients diagnosed with ACD at the Fundação de Medicina Tropical Doutor Heitor Vieira Dourado (FMT-HVD) were included. RESULTS: There were 147 cases of acute CD registered from 10 outbreaks that occurred in the state of Amazonas between 2004 and 2022. The transmission pathway was through oral route, with probable contaminated palm fruit juice (açaí and/or papatuá), and involved people from the same family, friends or neighbours. Of 147 identified cases, 87 (59%) were males; cases were aged 10 months to 82 years. The most common symptom was the febrile syndrome (123/147; 91.8%); cardiac alterations were present in 33/100 (33%), (2/147; 1.4%) had severe ACD with meningoencephalitis, and 12 (8.2%) were asymptomatic. Most cases were diagnosed through thick blood smear (132/147; 89.8%), a few (14/147; 9.5%) were diagnosed by serology and (1/147; 0.7%) by polymerase chain reaction (PCR) and blood culture. In all these outbreaks, 74.1% of the patients were analysed by PCR, and Trypanosoma cruzi TcIV was detected in all of them. No deaths were recorded. The incidence of these foci coincided with the fruit harvest period in the state of Amazonas. CONCLUSION: The occurrence of ACD outbreaks in the Amazon affected individuals of both sexes, young adults, living in rural and peri-urban areas and related to the consumption of regional foods. Early diagnosis is an important factor in surveillance. There was a low frequency of cardiac alterations. Continuous follow-up of most patients was not carried out due to difficulty in getting to specialised centres; therefore, little is known about post-treatment.

Treatment of cutaneous leishmaniasis with a sequential scheme of pentamidine and tamoxifen in an area with a predominance of Leishmania (Viannia) guyanensis: A randomised, non-inferiority clinical trial.

OBJECTIVE: To determine whether a combination of a single intramuscular (IM) dose of pentamidine (7 mg/kg) followed by oral tamoxifen 40 mg/day for 20 days is non-inferior to three IM doses of pentamidine 7 mg/kg in the treatment of cutaneous leishmaniasis with a margin of 15%. METHODS: Phase II, randomised, controlled, open-label, non-inferiority clinical trial. Primary outcome was the complete healing of the lesions 6 months after starting treatment. Secondary outcomes were healing 3 months after starting treatment and determining the presence and severity of adverse effects (AE). RESULTS: The research was concluded with 49 patients; Leishmania (Viannia) guyanensis was the most frequent species isolated. In the primary outcome, 18 (72%) (95% CI: 52.4%-85.7%) of the 25 patients allocated to the intervention group and 24 (100%) (95% CI: 86.2%-100%) of the control group (p = 0.015) met the established criteria of cure. There was no AE with tamoxifen. CONCLUSION: Although a 72% cure rate presented by the combination of tamoxifen and pentamidine was lower than in the control group that achieved a 100% cure, it is still a safe and is a clinically relevant result. It indicates that the therapeutic scheme evaluated may be a promising option for populations in remote areas, however it should be further studied, in order to include a larger number of patients.

Effect of femoral stem surface coating on clinical and radiographic outcomes of cementless primary total hip arthroplasty: a patient-matched retrospective study.

PURPOSE: This study aims to determine whether changing the stem coating grants superior outcomes at a minimum follow-up of five years. METHODS: Retrospective review of a consecutive series of primary total hip arthroplasties (THAs) operated by direct anterior approach between 01/01/2013 and 31/12/2014. Two stems were compared, which were identical except for their surface coating; "the Original stem" was fully coated with hydroxyapatite (HA), while "the ProxCoat stem" was proximally coated with plasma-sprayed titanium and HA. Matching was performed. Clinical assessment included modified Harris hip score (mHHS), Oxford hip score (OHS), and forgotten joint score (FJS). Radiographic assessment evaluated alignment, subsidence, pedestal formation, heterotopic ossification, radiolucent lines ≥ 2 mm, spot welds, cortical hypertrophy, and osteolysis. RESULTS: 232 hips received the Original stem and 167 the ProxCoat stem, from which respectively five hips (2.2%) and no hips (0%) underwent revision. Matching identified two groups of 91 patients, with comparable patient demographics. At > five years follow-up, there were no differences in OHS (16 ± 6 vs 15 ± 5; p = 0.075) nor FJS (81 ± 26 vs 84 ± 22; p = 0.521), but there were differences in mHHS (89 ± 15 vs 92 ± 12; p = 0.042). There were no differences in alignment, subsidence, pedestal formation, heterotopic ossification, cortical hypertrophy, and osteolysis. There were differences in prevalence of proximal radiolucent lines (12% vs 0%; p < 0.001) and distal spot welds (24% vs 54%; p < 0.001). CONCLUSION: At a minimum follow-up of five years, this study on matched patients undergoing primary THA found that ProxCoat stems results in significantly fewer radiolucent lines, more spot welds, and less revisions than Original stems, thus suggesting better bone ingrowth.

S-Locus Genotyping in Japanese Plum by High Throughput Sequencing Using a Synthetic S-Loci Reference Sequence.

Self-incompatibility in Prunus species is governed by a single locus consisting of two highly multi-allelic and tightly linked genes, one coding for an F-box protein-i.e., SFB in Prunus- controlling the pollen specificity and one coding for an S-RNase gene controlling the pistil specificity. Genotyping the allelic combination in a fruit tree species is an essential procedure both for cross-based breeding and for establishing pollination requirements. Gel-based PCR techniques using primer pairs designed from conserved regions and spanning polymorphic intronic regions are traditionally used for this task. However, with the great advance of massive sequencing techniques and the lowering of sequencing costs, new genotyping-by-sequencing procedures are emerging. The alignment of resequenced individuals to reference genomes, commonly used for polymorphism detection, yields little or no coverage in the S-locus region due to high polymorphism between different alleles within the same species, and cannot be used for this purpose. Using the available sequences of Japanese plum S-loci concatenated in a rosary-like structure as synthetic reference sequence, we describe a procedure to accurately genotype resequenced individuals that allowed the analysis of the S-genotype in 88 Japanese plum cultivars, 74 of them are reported for the first time. In addition to unraveling two new S-alleles from published reference genomes, we identified at least two S-alleles in 74 cultivars. According to their S-allele composition, they were assigned to 22 incompatibility groups, including nine new incompatibility groups reported here for the first time (XXVII-XXXV).

Astroglial S100B Secretion Is Mediated by Ca2+ Mobilization from Endoplasmic Reticulum: A Study Using Forskolin and DMSO as Secretagogues.

S100B, a homodimeric Ca2+-binding protein, is produced and secreted by astrocytes, and its extracellular levels have been used as a glial marker in brain damage and neurodegenerative and psychiatric diseases; however, its mechanism of secretion is elusive. We used primary astrocyte cultures and calcium measurements from real-time fluorescence microscopy to investigate the role of intracellular calcium in S100B secretion. In addition, the dimethyl sulfoxide (DMSO) effect on S100B was investigated in vitro and in vivo using Wistar rats. We found that DMSO, a widely used vehicle in biological assays, is a powerful S100B secretagogue, which caused a biphasic response of Ca2+ mobilization. Our data show that astroglial S100B secretion is triggered by the increase in intracellular Ca2+ and indicate that this increase is due to Ca2+ mobilization from the endoplasmic reticulum. Also, blocking plasma membrane Ca2+ channels involved in the Ca2+ replenishment of internal stores decreased S100B secretion. The DMSO-induced S100B secretion was confirmed in vivo and in ex vivo hippocampal slices. Our data support a nonclassic vesicular export of S100B modulated by Ca2+, and the results might contribute to understanding the mechanism underlying the astroglial release of S100B.

Satisfactory clinical and radiographic outcomes following revision total hip arthroplasty by direct anterior approach using primary femoral stems at 2-8 years of follow-up.

INTRODUCTION: To report clinical and radiographic outcomes of revision total hip arthroplasty (THA) through the direct anterior approach (DAA) using primary stems. MATERIALS AND METHODS: The authors assessed a consecutive series of revision THAs operated by DAA using primary (cemented and uncemented) stems between 1/1/2010 and 30/06/2017. The initial cohort comprised 47 patients (50 hips), aged 65 ± 10 years with BMI of 25 ± 4 kg/m2. Clinical assessment included modified Harris Hip Score (mHHS) and satisfaction with surgery. Radiographic assessment included radiolucent lines > 2 mm, bone remodelling, cortical hypertrophy, pedestal formation, and osteolysis. Linear regression analyses were performed. RESULTS: Of the 50 hips (47 patients) in the initial cohort, intraoperative complications that did not require re-revision occurred in 5 hips. At a follow-up of > 2 years: 5 hips (10%) were lost to follow-up and 3 hips (6%) required stem re-revision, leaving a final cohort of 42 hips (40 patients). Postoperative complications that did not require re-revision occurred in 4 hips (8%). At 4.3 ± 1.6 years, post-revision mHHS was 89 ± 14 (range 47-100) and 38 patients were satisfied or very satisfied with revision surgery. Bone remodelling was observed in 8 hips (16%), cortical hypertrophy in 6 hips (12%), grade I heterotopic ossification in 7 hips (14%), and grade II in 1 hip (2%). There were no cases of radiolucent lines, pedestal formation, or osteolysis. Regression analyses revealed that post-revision mHHS was not associated with any variable. CONCLUSIONS: Revision THA performed through the DAA using primary stems grants satisfactory clinical and radiographic outcomes at a minimum follow-up of two years.

[Update on the Diagnosis and Stratification of Patients with Acute Myeloid Leukemia: An Urgent National Need]. / Actualización en el diagnóstico y estratificación de pacientes con Leucemia Mieloide Aguda: una necesidad país imperiosa.

Acute myeloid leukemia is a neoplasm with a high lethality, with alarming results in our country, positioning it as a priority from the point of view of oncological public health. Cytology, immunophenotype, karyogram, and a few translocations/mutations by molecular biology are currently available for diagnosis and stratification. This diagnostic approach is insufficient since it allows classifying less than 50% of patients in a specific group. Therefore, consolidation therapy is selected with little biological information. The role of morphology and cytogenetics is progressively losing prognostic weight with respect to molecular biology, and next-generation sequencing has positioned itself as a key element for diagnosing our patients. In addition, the investigation of germline mutations is acquiring greater relevance, increasing its detection frequency and influencing decision-making regarding treatment and selecting a related donor for an allogeneic transplant. In this review, an update of the integrated diagnosis of patients with acute myeloid leukemia is carried out in light of the new diagnostic (WHO 2022 and ICC 2022), and prognostic classifications (ELN 2022). We propose an algorithm for integrated diagnosis to be considered for its implementation. It is imperative as a country to invest in new diagnostic technologies to improve the prognosis of our patients.

Measurement properties of the EQ-5D-Y administered through a smartphone app in children with asthma: a longitudinal questionnaire study.

BACKGROUND: Asthma impacts children's physical, emotional, and psychosocial Health-Related Quality of Life (HRQL). The EQ-5D-Y is a generic econometric instrument developed to measure HRQL in children. OBJECTIVE: Evaluation of feasibility, validity, reliability, and responsiveness of EQ-5D-Y descriptive system and utility index to allow the assessment of HRQL in children with asthma, aged 8-11 years (self-response version) or under 8 years old (proxy-response version). METHODS: We used data from baseline to 10 months of follow-up of an observational, prospective study of children with persistent asthma recruited by pediatricians in Spain (2018-2020). HRQL instruments were administered through a smartphone application: ARCA app. The EQ-5D-Y is composed of a 5-dimension descriptive system, a utility index ranging from 1 to - 0.5392, and a general health visual analogue scale (EQ-VAS). The Pediatric Asthma Impact Scale (PROMIS-PAIS) includes 8 items, providing a raw score. Construct validity hypotheses were stated a priori, and evaluated following two approaches, multitrait-multimethod matrix and known groups' comparisons. Reliability and responsiveness subsamples were defined by stability or change in EQ-VAS and the Asthma Control Questionnaire (ACQ), to estimate the intraclass correlation coefficient (ICC) and the magnitude of change over time. RESULTS: The EQ-5D-Y was completed at baseline for 119 children (81 self-responded and 38 through proxy response), with a mean age of 9.1 (1.7) years. Mean (SD) of the EQ-5D-Y utility index was 0.93 (0.11), with ceiling and floor effects of 60.3% and 0%, respectively. Multitrait-multimethod matrix confirmed the associations previously hypothesized for the EQ-5D-Y utility index [moderate with PROMIS-PAIS (0.38) and weak with ACQ (0.28)], and for the EQ-5D-Y dimension "problems doing usual activities" [moderate with the ACQ item (0.35) and weak with the PROMIS-PAIS item (0.17)]. Statistically significant differences were found in the EQ-5D-Y between groups defined by asthma control, reliever inhalers use, and second-hand smoke exposure, with mostly moderate effect sizes (0.45-0.75). The ICC of the EQ-5D-Y utility index in the stable subsamples was high (0.81 and 0.79); and responsiveness subsamples presented a moderate to large magnitude of change (0.68 and 0.78), though without statistical significance. CONCLUSIONS: These results support the use of the EQ-5D-Y as a feasible, valid, and reliable instrument for evaluating HRQL in children with persistent asthma. Further studies are needed on the responsiveness of the EQ-5D-Y in this population.

Evolutionarily informed deep learning methods for predicting relative transcript abundance from DNA sequence.

Deep learning methodologies have revolutionized prediction in many fields and show potential to do the same in molecular biology and genetics. However, applying these methods in their current forms ignores evolutionary dependencies within biological systems and can result in false positives and spurious conclusions. We developed two approaches that account for evolutionary relatedness in machine learning models: (i) gene-family-guided splitting and (ii) ortholog contrasts. The first approach accounts for evolution by constraining model training and testing sets to include different gene families. The second approach uses evolutionarily informed comparisons between orthologous genes to both control for and leverage evolutionary divergence during the training process. The two approaches were explored and validated within the context of mRNA expression level prediction and have the area under the ROC curve (auROC) values ranging from 0.75 to 0.94. Model weight inspections showed biologically interpretable patterns, resulting in the hypothesis that the 3' UTR is more important for fine-tuning mRNA abundance levels while the 5' UTR is more important for large-scale changes.

The interplay between α7 nicotinic acetylcholine receptors, pannexin-1 channels and P2X7 receptors elicit exocytosis in chromaffin cells.

Pannexin-1 (Panx1) forms plasma membrane channels that allow the exchange of small molecules between the intracellular and extracellular compartments, and are involved in diverse physiological and pathological responses in the nervous system. However, the signaling mechanisms that induce their opening still remain elusive. Here, we propose a new mechanism for Panx1 channel activation through a functional crosstalk with the highly Ca2+ permeable α7 nicotinic acetylcholine receptor (nAChR). Consistent with this hypothesis, we found that activation of α7 nAChRs induces Panx1-mediated dye uptake and ATP release in the neuroblastoma cell line SH-SY5Y-α7. Using membrane permeant Ca2+ chelators, total internal reflection fluorescence microscopy in SH-SY5Y-α7 cells expressing a membrane-tethered GCAMP3, and Src kinase inhibitors, we further demonstrated that Panx1 channel opening depends on Ca2+ signals localized in submembrane areas, as well as on Src kinases. In turn, Panx1 channels amplify cytosolic Ca2+ signals induced by the activation of α7 nAChRs, by a mechanism that seems to involve ATP release and P2X7 receptor activation, as hydrolysis of extracellular ATP with apyrase or blockage of P2X7 receptors with oxidized ATP significantly reduces the α7 nAChR-Ca2+ signal. The physiological relevance of this crosstalk was also demonstrated in neuroendocrine chromaffin cells, wherein Panx1 channels and P2X7 receptors contribute to the exocytotic release of catecholamines triggered by α7 nAChRs, as measured by amperometry. Together these findings point to a functional coupling between α7 nAChRs, Panx1 channels and P2X7 receptors with physiological relevance in neurosecretion.

The Selvester QRS score as an estimative of myocardial injury in acute chagasic patients from the Brazilian Amazon.

BACKGROUND: In the Brazilian Amazon, a new epidemiological profile of Chagas disease transmission, the oral route, has been detected and cited as being responsible for the increase in acute cases in Brazil. The clinical evaluation of acute Chagas disease (ACD) has been a challenge since it can progress to a chronic phase with cardiac alterations, and the follow-up by modern diagnostic methods is very difficult due to the socio-geographical characteristics of the Brazilian Amazon. Thus, alternatives should be sought to alleviate this problem. We conducted a study to evaluate subjects with ACD using the 12-lead ECG QRS score (Selvester score) as an estimative of myocardial injury progression before and after ACD treatment. METHODS: The study included indigenous subjects from the Amazon region with ACD in clinical follow-up at the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD) Chagas Disease outpatient clinic in the state of Amazonas, Brazil. The control group consisted of 31 healthy volunteers with no history of heart disease and no reactive serology for Chagas disease. Baseline ECG was performed in all subjects. The Selvester scoring method was performed according to the standardized guide (< 3 points: no myocardial injury,> 3: points × 3% = % of the predicted LV infarction). RESULTS: A total of 62 subjects were included, 31 as cases and 31 as controls. The mean follow-up of the case group was 17 months. The control group presented normal ECG. The case group presented 13 alterations before treatment and 11 after. Nineteen individuals presented scores > 3 points, 6 before and 13 after. In 19.36% of subjects, myocardial injury was found before treatment and in 41.94% after treatment. CONCLUSION: This is the first study that uses the Selvester score (SS) to predict myocardial injury in subjects with ACD. The results of this study suggest the significant presence of myocardial injury from the beginning of treatment to the period post treatment of ACD, which demonstrates that the SS can be applied for stratification and follow-up of Chagas disease in the Amazon region.

Does Cup Position at the High Hip Center or Anatomic Hip Center in THA for Developmental Dysplasia of the Hip Result in Better Harris Hip Scores and Revision Incidence? A Systematic Review.

BACKGROUND: One goal of THA is to restore the anatomic hip center, which can be achieved in hips with developmental dysplasia by placing cups at the level of the native acetabulum. However, this might require adjuvant procedures such as femoral shortening osteotomy. Another option is to place the cup at the high hip center, potentially reducing surgical complexity. Currently, no clear consensus exists regarding which of these cup positions might offer better functional outcomes or long-term survival. QUESTION/PURPOSE: We performed a systematic review to determine whether (1) functional outcomes as measured by the Harris hip score, (2) revision incidence, and (3) complications that do not result in revision differ based on the position of the acetabular cup (high hip center versus anatomic hip center) in patients undergoing THA for developmental dysplasia of the hip (DDH). METHODS: We performed a systematic review using Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, including studies comparing the functional outcomes, revision incidence, and complications of primary THA in dysplastic hips with acetabular cups placed at the high hip center versus those placed at the anatomic hip center, over any time frame. The review protocol was registered with PROSPERO (registration number CRD42020168183) before commencement. Of 238 records, eight comparative, retrospective nonrandomized studies of interventions were eligible for our systematic review, reporting on 207 hips with cups placed at the high hip center and 268 hips with cups at the anatomic hip center. Risk of bias within eligible studies was assessed using the Risk Of Bias In Non-randomized Studies of Interventions tool. Due to low comparability between studies, data could not be pooled, so these studies were assessed without summary effects. RESULTS: Six studies compared Harris hip scores, two of which favored high hip center cup placement and three of which favored anatomic hip center cup placement, although none of the differences between cohorts met the minimum clinically important difference. Five studies reliably compared revision incidence, which ranged from 2% to 9% for high hip center at 7 to 15 years and 0% to 5.9% for anatomic hip center at 6 to 16 years. Five studies reported intra- and postoperative complications, with the high hip center being associated with higher incidence of dislocation and lower incidence of neurological complications. No clear difference was observed in intraoperative complications between the high hip center and anatomic hip center. CONCLUSION: No obvious differences could be observed in Harris hip score or revision incidence after THA for osteoarthritis secondary to DDH between cups placed at the anatomic hip center and those placed at the high hip center. Placement of the acetabular cup in the high hip center may lead to higher risk of dislocation but lower risk of neurologic complications, although no difference in intraoperative complications was observed. Surgeons should be able to achieve satisfactory functional scores and revision incidence using either technique, although they should be aware of how their choice influences hip biomechanics and the need for adjunct procedures and associated risks and operative time. These recommendations should be considered with respect to the several limitations in the studies reviewed, including the presence of serious confounding factors and selection biases, inconsistent definitions of the high hip center, variations in dysplasia severity, small sample sizes, and follow-up periods. These weaknesses should be addressed in well-designed future studies. LEVEL OF EVIDENCE: Level III, therapeutic study.

Endoscopic Tenotomy for Iliopsoas Tendinopathy Following Total Hip Arthroplasty Can Relieve Pain Regardless of Acetabular Cup Overhang or Anteversion.

PURPOSE: To report outcomes of endoscopic iliopsoas tenotomy (EIT) in patients with iliopsoas tendinopathy following total hip arthroplasty (THA) and determine whether improvements in clinical scores are associated with acetabular cup anteversion measured on plain radiographs or overhang measured using established and alternative computed tomography (CT)-based methods. METHODS: We evaluated patients who underwent EIT for iliopsoas tendinopathy after THA (2014-2017), performed between the lesser trochanter and psoas valley. Indications were groin pain during active hip flexion, exclusion of other complications, and no pain relief after 6 months of conservative treatment. Pretenotomy inclination and anteversion were measured on radiographs; sagittal and axial overhang were measured on CT scans on slices passing through: (Method 1) prosthetic head center and (Method 2) anterior margin of acetabular cup. Modified Harris hip score (mHHS), Oxford Hip Score (OHS), and level of groin pain were recorded at 12 or more months. Wilcoxon signed-rank tests were used to compare pre- and post-tenotomy scores, and intraclass correlation coefficients (ICCs) to assess intermethod agreement. RESULTS: The cohort comprised 16 men (17 hips) and 32 women (33 hips), aged 60.8 ± 10.5 years at EIT. For the 30 (60%) hips that had pretenotomy CT scans, axial and sagittal overhang were, respectively, 3.4 ± 3.7 mm and 4.6 ± 4.6 mm, using Method 1, compared with 3.9 ± 3.9 mm and 6.9 ± 5.0 mm using Method 2. Intermethod agreement was good for axial (ICC, 0.67; P < .001) and sagittal (ICC, 0.68; P < .001) overhang. At a minimum 1 year after EIT, 3 hips had cup and stem revision and 1 hip had isolated cup revision, leaving 46 hips for clinical assessment. No complications were noted. mHHS improved by 26 ± 19 (P < .001) and OHS improved by 20 ± 11 (P < .001). Twenty-six hips (57%) achieved the patient acceptable symptom state for mHHS, whereas 42 hips (91%) achieved the patient acceptable symptom state for OHS. Post-tenotomy groin pain was slight in 15%, mild in 17%, and moderate in 11%. Regression analyses revealed no associations between clinical scores and overhang/anteversion. CONCLUSIONS: For patients with iliopsoas tendinopathy following THA, endoscopic iliopsoas tenotomy granted clinically important improvements of mHHS in 76% and OHS in 89%, despite moderate residual groin pain in 11%. Improvements in clinical scores did not seem to be associated with the extent of cup overhang or anteversion in the cases for which adequate preoperative imaging was available. LEVEL OF EVIDENCE: Level IV, retrospective cohort study.

Systemic lupus erythematosus in the intensive care unit: a systematic review.

Systemic lupus erythematosus (SLE) is an autoimmune disease with heterogeneous pathophysiologic mechanisms and diverse clinical manifestations. SLE is a frequent cause of intensive care unit (ICU) admissions. Multiple studies with controversial findings on the causes, evolution and outcomes of ICU-admitted patients with SLE have been published. The aim of this paper is to review the literature reporting the clinical characteristics and outcomes, such as mortality and associated factors, in such patients. Among the main causes of ICU admissions are SLE disease activity, respiratory failure, multi-organ failure and infections. The main factors associated with mortality are a high Acute Physiology and Chronic Health Evaluation (APACHE) score, the need for mechanical ventilation, and vasoactive and inotropic agent use. Reported mortality rates are 18.4%-78.5%. Therefore, it is important to evaluate SLE disease severity for optimizing clinical management and patient outcomes.

Clinical characterization, outcomes, and prognosis in patients with systemic lupus erythematosus admitted to the intensive care unit.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a clinically heterogeneous autoimmune disease, and in some conditions, admission to the intensive care unit (ICUs) is required. This study describes the clinical and prognostic factors in SLE patients admitted to the ICU. METHODS: We conducted a retrospective study that reviewed all clinical records of patients with SLE admitted to the ICU between 2011 and 2018. RESULTS: We evaluated 188 patients, with 279 ICU admissions. Most patients were female (n = 159; 84.57%) with a median age of 35 years (interquartile range (IQR) = 25-48 years). Infection was the leading cause of admission in 77 (27.60%) cases, followed by lupus flare. The average length of hospitalization was 5 days (IQR 3-11 days), and the SLE Disease Activity Index 2000, Acute Physiology, Age and Chronic Health Evaluation (APACHE II), and Sequential Organ Failure Assessment (SOFA) scores were 9 (IQR 2-17), 14 (IQR 10-17), and 3 (IQR 2-5), respectively. Non-survivors presented with higher APACHE II and SOFA scores. Infection was the leading cause of mortality (n = 38; 20.21%), and predictors of mortality included invasive mechanical ventilation, vasoactive medication requirement, higher SOFA scores, and antiphospholipid syndrome comorbidity. CONCLUSIONS: We found that infection was the leading cause of ICU admissions and mortality in patients with SLE. Factors identified here as predictors of mortality should be accurately identified at admission for the prompt treatment of SLE patients.

Promising outcomes of hip mosaicplasty by minimally invasive anterior approach using osteochondral autografts from the ipsilateral femoral head.

PURPOSE: Recent studies demonstrated promising results of mosaicplasty for femoral head osteochondral lesions using posterior and lateral approaches. This study aimed to evaluate outcomes of mosaicplasty using ipsilateral femoral head autografts by minimally invasive anterior approach. The hypothesis was that this surgical technique would grant satisfactory clinical outcomes with considerable improvement of clinical scores. METHODS: A consecutive series of 27 mosaicplasties, to treat osteochondral lesions of the femoral head measuring 1.6 ± 0.7 cm2 (range 0.8-4.0) in patients aged 28.7 ± 7.4 years (range 19-44), was evaluated using the mHHS and WOMAC scores at minimum follow-up of 12 months. All patients were operated by minimally invasive anterior (Hueter) approach and osteochondral plugs were harvested from the non-weight-bearing portion of the femoral head. Adjuvant osteoplasty was necessary for some patients at the acetabulum (n = 3), femur (n = 14) or both (n = 2). RESULTS: Three patients were excluded due to concomitant periacetabular osteotomies or shelf procedures, one patient could not be reached, and another was revised to THA. This left 22 patients for clinical assessment at 39.4 ± 23.2 months (12.0-90.2). Their mHHS improved from 56.3 ± 12.6 to 88.4 ± 9.9, and WOMAC improved from 45.1 ± 16.9 to 80.6 ± 13.0. Two patients (8.4%) underwent arthroscopy at 13 and 30 months to remove painful residual cam-type deformities. Regression analyses revealed that net improvement in WOMAC decreased with lesion size (p = 0.002) and increased with follow-up (p = 0.004). CONCLUSIONS: Hip mosaicplasty using autografts from the ipsilateral femoral head, performed by minimally invasive anterior approach, granted satisfactory outcomes and functional improvements. Caution is, however, advised for lesions > 2 cm2 (diameter > 16 mm) which may be a threshold limit for this procedure. LEVEL OF EVIDENCE: Level IV, Case series.