In vivo reduction of RAD51-mediated homologous recombination triggers aging but impairs oncogenesis.

Homologous recombination (HR) is a prominent DNA repair pathway maintaining genome integrity. Mutations in many HR genes lead to cancer predisposition. Paradoxically, the implication of the pivotal HR factor RAD51 on cancer development remains puzzling. Particularly, no RAD51 mouse models are available to address the role of RAD51 in aging and carcinogenesis in vivo. We engineered a mouse model with an inducible dominant-negative form of RAD51 (SMRad51) that suppresses RAD51-mediated HR without stimulating alternative mutagenic repair pathways. We found that in vivo expression of SMRad51 led to replicative stress, systemic inflammation, progenitor exhaustion, premature aging and reduced lifespan, but did not trigger tumorigenesis. Expressing SMRAD51 in a breast cancer predisposition mouse model (PyMT) decreased the number and the size of tumors, revealing an anti-tumor activity of SMRAD51. We propose that these in vivo phenotypes result from chronic endogenous replication stress caused by HR decrease, which preferentially targets progenitors and tumor cells. Our work underlines the importance of RAD51 activity for progenitor cell homeostasis, preventing aging and more generally for the balance between cancer and aging.

Publisher Correction: Progenitors from the central nervous system drive neurogenesis in cancer.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Progenitors from the central nervous system drive neurogenesis in cancer.

Autonomic nerve fibres in the tumour microenvironment regulate cancer initiation and dissemination, but how nerves emerge in tumours is currently unknown. Here we show that neural progenitors from the central nervous system that express doublecortin (DCX+) infiltrate prostate tumours and metastases, in which they initiate neurogenesis. In mouse models of prostate cancer, oscillations of DCX+ neural progenitors in the subventricular zone-a neurogenic area of the central nervous system-are associated with disruption of the blood-brain barrier, and with the egress of DCX+ cells into the circulation. These cells then infiltrate and reside in the tumour, and can generate new adrenergic neurons. Selective genetic depletion of DCX+ cells inhibits the early phases of tumour development in our mouse models of prostate cancer, whereas transplantation of DCX+ neural progenitors promotes tumour growth and metastasis. In humans, the density of DCX+ neural progenitors is strongly associated with the aggressiveness and recurrence of prostate adenocarcinoma. These results reveal a unique crosstalk between the central nervous system and prostate tumours, and indicate neural targets for the treatment of cancer.

Trends in the treatment of proximal humerus fractures from 2010 to 2020.

BACKGROUND: The incidence of proximal humerus fractures (PHF) is continuing to rise due to shifts towards a more aged population as well as advancements in surgical treatment options. The purpose of this study is to examine and compare trends in the treatment of PHFs (nonoperative vs. operative; different surgical treatments) across different age groups over the last decade (2010-2020). METHODS: The New York Statewide Planning and Research Cooperative System (SPARCS) database was queried using International Classification of Diseases and Current Procedural Terminology codes to identify all patients presenting with or undergoing surgery for PHF between 2010 and 2020. Treatment trends, demographics, and insurance information were analyzed during the study period. Comparisons were made between operative and nonoperative trends with respect to the number and type of surgeries performed among 3 age groups: ≤49 years, 50-64 years, and ≥65 years. The rate of postoperative complications and reoperations was evaluated and compared among different surgical treatments for patients with a minimum 1-year postoperative follow-up. RESULTS: A total of 92,308 patients with a mean age of 67.8 ± 16.8 years were included. Over the last decade, there was no significant increase in the percentage of PHFs treated with surgery. A total of 15,523 PHFs (16.82%) were treated operatively, and these patients, compared with the nonoperative cohort, were younger (64.9 years vs. 68.4 years, P < .001), more likely to be White (80.2% vs. 74.7%, P < .001), and more likely to have private insurance (41.4% vs. 32.0%, P < .001). For patients ≤49 years old, trends in operative treatment have remained stable with internal fixation (IF) as the most used surgical modality. For patients 50-64 years old, we observed a gradual decline in the use of hemiarthroplasty (HA), with a corresponding increase in the use of reverse total shoulder arthroplasty (rTSA), but IF continued to be the most used operative modality. In patients over 65 years, a steep decline in the use of IF and HA was noted during the first half of the decade along with a significant exponential increase in the use of rTSA, which surpassed the use of IF in 2019. Despite the increase in the use of rTSA, no differences in rate of surgical complications were noted between rTSA and IF (χ2 = 0.245, P = .621) or reoperations (χ2 = 0.112, P = .730). CONCLUSION: Nonsurgical treatment remains the mainstay treatment of PHFs. Although there is no increase in the prevalence of operative treatment in patients ≥50 years in the last decade, there is an exponential increase in the use of rTSA with a corresponding decrease in HA and IF, a trend more substantial in patients ≥65 years compared with patients between 50 and 64 years.

A genetic variant controls interferon-ß gene expression in human myeloid cells by preventing C/EBP-ß binding on a conserved enhancer.

Interferon ß (IFN-ß) is a cytokine that induces a global antiviral proteome, and regulates the adaptive immune response to infections and tumors. Its effects strongly depend on its level and timing of expression. Therefore, the transcription of its coding gene IFNB1 is strictly controlled. We have previously shown that in mice, the TRIM33 protein restrains Ifnb1 transcription in activated myeloid cells through an upstream inhibitory sequence called ICE. Here, we show that the deregulation of Ifnb1 expression observed in murine Trim33-/- macrophages correlates with abnormal looping of both ICE and the Ifnb1 gene to a 100 kb downstream region overlapping the Ptplad2/Hacd4 gene. This region is a predicted myeloid super-enhancer in which we could characterize 3 myeloid-specific active enhancers, one of which (E5) increases the response of the Ifnb1 promoter to activation. In humans, the orthologous region contains several single nucleotide polymorphisms (SNPs) known to be associated with decreased expression of IFNB1 in activated monocytes, and loops to the IFNB1 gene. The strongest association is found for the rs12553564 SNP, located in the E5 orthologous region. The minor allele of rs12553564 disrupts a conserved C/EBP-ß binding motif, prevents binding of C/EBP-ß, and abolishes the activation-induced enhancer activity of E5. Altogether, these results establish a link between a genetic variant preventing binding of a transcription factor and a higher order phenotype, and suggest that the frequent minor allele (around 30% worldwide) might be associated with phenotypes regulated by IFN-ß expression in myeloid cells.

Minimal clinically important difference (MCID) and substantial clinical benefit (SCB) of upper extremity PROMIS scores following arthroscopic rotator cuff repairs.

PURPOSE: To calculate and determine what factors are associated with achieving the Minimal Clinically Important Difference (MCID) and the Substantial Clinical Benefit (SCB) of Patient-Reported Outcomes Measurement Information System (PROMIS) Upper Extremity Computer Adaptive Testing v2.0 (UE), Pain Interference (P-Interference), and Pain Intensity (P-Intensity) in patients undergoing arthroscopic rotator cuff repair (aRCR). METHODS: The change in PROMIS scores representing the optimal cutoff for a ROC curve with an area under the curve analysis was used to calculate the anchor-based MCID and SCB. To assess the responsiveness of each PROM, effect sizes and standardized response means (SRM) were calculated. To identify factors associated with attaining the MCID and SCB, univariate and multivariate logistic regression analyses were performed. RESULTS: A total of 323 patients with an average age of 59.9 ± 9.5 were enrolled in this study, of which, 187/323 [57.9%] were male and 136/323 [42.1%] were female. The anchor-based MCID for PROMIS UE, P-Interference, and P-Intensity was: 9.0, 7.5, and 11.2, respectively. The respective SCB was 10.9, 9.3, and 12.7. Effect size and SRM were: PROMIS UE (1.4, 1.3), P-Interference (1.8, 1.5), and P-Intensity (2.3, 2.0). Lower preoperative P-Intensity scores (p = 0.02), dominant arm involvement (p = 0.03), and concomitant biceps tenodesis (p = 0.03) were associated with patients achieving the SCB for PROMIS UE. CONCLUSION: A large responsiveness for each of the PROMIS instruments due to the majority of patients reporting great improvement after aRCR and a small standard deviation across all outcome measures was shown in our study. Lower preoperative P-Intensity scores and concomitant biceps tenodesis were associated with higher odds of achieving the SCB for PROMIS UE. The knowledge of MCID and SCB values for PROMIS instruments will allow the surgeon to determine whether the improvements in the PROMIS scores after aRCR are clinically meaningful. LEVEL OF EVIDENCE: Level III.

Analysis of patient factors associated with selection of corticosteroid injection in the freezing phase of idiopathic adhesive capsulitis.

BACKGROUND: Primary idiopathic adhesive capsulitis (AC) is characterized by shoulder pain and global limitations in range of motion (ROM). The aim of this study was to determine (1) if a spectrum of symptom severity exists during the freezing phase of AC and (2) identify factors associated with patient selection of corticosteroid injection (CSI) for treatment. METHODS: Patients presenting within 6 months of symptom onset of AC (freezing phase) were enrolled in this single-site retrospective case control study. Visual analog pain scale (VAS) score, shoulder ROM, American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) scores, and Patient-Reported Outcomes Measurement Information System (PROMIS function and pain) scores were collected. Each patient was offered oral anti-inflammatory medication, physical therapy, and intra-articular CSI. Patients were divided into 2 cohorts: those electing vs. those deferring CSI. Multivariable logistic regression was performed to identify patient or symptom characteristics predictive of electing CSI. RESULTS: A total of 112 patients (mean age = 54.7 ± 8.8 years, female = 76 [67.9%], mean symptom duration = 13.2 ± 7.9 weeks, elected CSI = 74 [66.1%]) were included in our analysis. The overall study population demonstrated a wide spectrum of VAS pain scores (6.0 ± 2.8, range: 0-10) and ROM: forward elevation (99° ± 27°, range: 30°-150°), abduction (82° ± 24°, range: 30°-130°), external rotation (47° ± 13°, range: 0°-90°), internal rotation (38° ± 26°, range: 5°-90°). The CSI group had higher mean VAS pain score (6.6 ± 2.5 vs. 4.9 ± 3.0, P = .005) and greater limitations in ROM for forward elevation (92° ± 27° vs. 113° ± 25°, P = .001) and abduction (77° ± 24° vs. 90° ± 21°, P = .005) compared with the non-CSI cohort. The CSI group demonstrated significantly worse shoulder function based on Constant (P < .05), ASES (P = .001), P-UE (P = .016), P-Intensity (P = .002), and P-Interference (P = .004). Logistic regression demonstrated decreased total shoulder ROM in forward elevation and abduction plane (OR = 0.98, 95% CI = 0.97-0.99, P = .004). Hispanic ethnicity and increased VAS pain score (OR = 1.20, 95% CI = 1.01-1.43, P = .04) were associated with increased likelihood of electing CSI. CONCLUSION: A spectrum of symptom severity exists during the freezing phase of primary AC, despite similar etiology. AC patients with greater pain severity, and greater limitations in ROM at initial evaluation were associated with patient selection of CSI.

Inpatient charges, complication, and revision rates for shoulder arthroplasty in Parkinson disease: a regional database study.

BACKGROUND: Parkinson disease (PD) is an established risk factor for higher rates of complications and revision surgery following shoulder arthroplasty, yet the economic burden of PD remains to be elucidated. The purpose of this study is to compare rates of complication and revisions as well as inpatient charges for shoulder arthroplasty procedures between PD and non-PD patients using an all-payer statewide database. METHODS: Patients undergoing primary shoulder arthroplasty from 2010 to 2020 were identified from the New York (NY) Statewide Planning and Research Cooperative System (SPARCS) database. Study groups were assigned based on concomitant diagnosis of PD at the time of index procedure. Baseline demographics, inpatient data, and medical comorbidities were collected. Primary outcomes measured were accommodation, ancillary, and total inpatient charges. Secondary outcomes included postoperative complication and reoperation rates. Logistic regression was performed to evaluate effect of PD on shoulder arthroplasty revision and complication rates. All statistical analysis was performed using R. RESULTS: A total of 39,011 patients (429 PD vs. 38,582 non-PD) underwent 43,432 primary shoulder arthroplasties (477 PD vs. 42,955 non-PD) with mean follow-up duration of 2.9 ± 2.8 years. The PD cohort was older (72.3 ± 8.0 vs. 68.6 ± 10.4 years, P < .001), with greater male composition (50.8% vs. 43.0%, P = .001), and higher mean Elixhauser scores (1.0 ± 4.6 vs. 7.2 ± 4.3, P < .001). The PD cohort had significantly greater accommodation charges ($10,967 vs. $7,661, P < .001) and total inpatient charges ($62,000 vs. $56,000, P < .001). PD patients had significantly higher rates of revision surgery (7.7% vs. 4.2%, P = .002) and complications (14.1% vs. 10.5%, P = .040), as well as significantly higher incidences of readmission at 3 and 12 months postoperatively. After controlling for age and baseline comorbidities, PD patients had 1.64 times greater odds of reoperation compared to non-PD patients (95% CI 1.10, 2.37; P = .012) and a hazard ratio of 1.54 for reoperation when evaluating revision-free survival following primary shoulder arthroplasty (95% CI 1.07, 2.20; P = .019). CONCLUSIONS: PD confers a longer length of stay, higher rates of postoperative complications and revisions, and greater inpatient charges in patients undergoing TSA. Knowledge of the associated risks and resource requirements of this population will aid surgeons in their decision making as they continue to provide care to a growing number of patients affected by PD.

90-day outcomes and factors for complications following radial head arthroplasty for Mason Type III and IV radial head fractures.

PURPOSE: The aim of this study is to evaluate 90-day outcomes and complications following radial head arthroplasty (RHA) for Mason Type III and IV radial head fractures (RHFs) and determine factors predisposing patients to early complications and revision surgery. METHODS: Patients undergoing RHA for Mason Type III and IV RHFs were identified retrospectively from an institutional database. Postoperative complications, reoperations, elbow range of motion, radiographs and concomitant injuries on the ipsilateral upper extremity were reviewed. Additionally, injuries were sub-classified as low-energy trauma (LET) or high-energy trauma (HET). Univariate logistic regression was performed to evaluate the risk for complications using patient factors not limited to the presence of concomitant ligamentous or bony injuries. P values < 0.05 were considered statistically significant. RESULTS: Seventy four patients were included in our study with an average follow-up time of 12.7 months. Complications within 90-days of operation occurred in 8.1% of patients: heterotopic ossification (4.1%), superficial wound dehiscence (2.7%), and posterior interosseous nerve palsy (1.4%). No patients required readmission or revision surgery in the 90-day postoperative period. Univariate regression analysis did not demonstrate a significant association between diabetes, ASA status, HET versus LET, or the presence of concomitant injury. Concomitant injuries were found in 92% of patients. CONCLUSION: Radial head arthroplasty for RHFs demonstrates a low complication rate in the short-term. Diabetes, ASA class, high versus low energy trauma, and presence of concomitant injury were not found to be associated with higher complication rates in the 90-day postoperative period. LEVEL OF EVIDENCE: Level of evidence IV, retrospective case series.

The Utility of Lower Extremity Screening Duplex for the Detection of Deep Vein Thrombosis in Trauma.

BACKGROUND: Trauma patients are high-risk for venous thromboembolism (VTE). Lower extremity screening duplex ultrasonography (LESDUS) is controversial and not standardized for early VTE diagnosis. By implementing risk stratification and selective screening, we aim to optimize resource utilization. MATERIALS AND METHODS: A retrospective review were conducted at a Level-1 Trauma Center, January 2015-October 2019. LESDUS was performed within 72-h of presentation, then weekly. Demographics, VTE data, and outcomes were collected from the trauma registry. Risk assessment profile (RAP) score was calculated based on collected data. RESULTS: Of 5,645 patients included, 2,813 (49.8%) were screened for lower extremity deep vein thrombosis (LEDVT). Of 187 patients with LEDVT, 154 were diagnosed on LESDUS, 18 after negative LESDUS, and 15 in unscreened patients. Patients with VTE were older (61y versus 55, P < 0.01), more often male (70.9% versus 29.1%, P = 0.03), had higher ISS (16 versus 10, P < 0.01), longer hospital length of stay (LOS) (11.5 d versus 3, P < 0.01), longer ICU LOS (4.5 d versus 1, P < 0.01), and increased mortality (9.1% versus 4.3%, P = 0.01). RAP was higher in VTE patients versus those without (nine versus three, P < 0.01). RAP ≥8 was 62.5% sensitive and 70.4% specific for VTE. Chemoprophylaxis delay also correlated with increased VTE (OR = 1.48, 95% CI = 1.03-2.12). CONCLUSIONS: VTE remains a significant complication in trauma patients. Despite a universal LESDUS protocol, only 50% of patients underwent screening and 20% of all LE DVTs were not identified on LESDUS. To optimize resource utilization and protocol adherence, LESDUS should only be performed if RAP ≥8 or if unable to administer timely chemoprophylaxis.

Prion protein deficiency impairs hematopoietic stem cell determination and sensitizes myeloid progenitors to irradiation.

Highly conserved among species and expressed in various types of cells, numerous roles have been attributed to the cellular prion protein (PrPC). In hematopoiesis, PrPC regulates hematopoietic stem cell self-renewal but the mechanisms involved in this regulation are unknown. Here we show that PrPC regulates hematopoietic stem cell number during aging and their determination towards myeloid progenitors. Furthermore, PrPC protects myeloid progenitors against the cytotoxic effects of total body irradiation. This radioprotective effect was associated with increased cellular prion mRNA level and with stimulation of the DNA repair activity of the Apurinic/pyrimidinic endonuclease 1, a key enzyme of the base excision repair pathway. Altogether, these results show a previously unappreciated role of PrPC in adult hematopoiesis, and indicate that PrPC-mediated stimulation of BER activity might protect hematopoietic progenitors from the cytotoxic effects of total body irradiation.

A kinome-targeted RNAi-based screen links FGF signaling to H2AX phosphorylation in response to radiation.

A general radioprotective effect by fibroblast growth factor (FGF) has been extensively described since the early 1990s; however, the molecular mechanisms involved remain largely unknown. Radiation-induced DNA double-strand breaks (DSBs) lead to a complex set of responses in eukaryotic cells. One of the earliest consequences is phosphorylation of histone H2AX to form nuclear foci of the phosphorylated form of H2AX (γH2AX) in the chromatin adjacent to sites of DSBs and to initiate the recruitment of DNA-repair molecules. Upon a DSB event, a rapid signaling network is activated to coordinate DNA repair with the induction of cell-cycle checkpoints. To date, three kinases (ATM, ATR, and DNA-PK) have been shown to phosphorylate histone H2AX in response to irradiation. Here, we report a kinome-targeted small interfering RNA (siRNA) screen to characterize human kinases involved in H2AX phosphorylation. By analyzing γH2AX foci at a single-nucleus level, we identified 46 kinases involved either directly or indirectly in H2AX phosphorylation in response to irradiation in human keratinocytes. Furthermore, we demonstrate that in response to irradiation, the FGFR4 signaling cascade promotes JNK1 activation and direct H2AX phosphorylation leading, in turn, to more efficient DNA repair. This can explain, at least partially, the radioprotective effect of FGF.

Keap1-Nrf2 system regulates cell fate determination of hematopoietic stem cells.

Nrf2 is a major transcriptional activator of cytoprotective genes against oxidative/electrophilic stress, and Keap1 negatively regulates Nrf2. Emerging works have also suggested a role for Nrf2 as a regulator of differentiation in various cells, but the contribution of Nrf2 to the differentiation of hematopoietic stem cells (HSCs) remains elusive. Clarifying this point is important to understand Nrf2 functions in the development and/or resolution of inflammation. Here, we established two transgenic reporter mouse lines that allowed us to examine Nrf2 expression precisely in HSCs. Nrf2 was abundantly transcribed in HSCs, but its activity was maintained at low levels due to the Keap1-mediated degradation of Nrf2 protein. When we characterized Keap1-deficient mice, their bone marrow cells showed enhanced granulocyte-monocyte differentiation at the expense of erythroid and lymphoid differentiation. Importantly, Keap1-null HSCs showed lower expression of erythroid and lymphoid genes than did control HSCs, suggesting granulocyte-monocyte lineage priming in Keap1-null HSCs. This abnormal lineage commitment was restored by a concomitant deletion of Nrf2, demonstrating the Nrf2-dependency of the skewing. Analysis of Nrf2-deficient mice revealed that the physiological level of Nrf2 is sufficient to contribute to the lineage commitment. This study unequivocally shows that the Keap1-Nrf2 system regulates the cell fate determination of HSCs.

Impaired functionality and homing of Fancg-deficient hematopoietic stem cells.

Fanconi anemia (FA) is a human rare genetic disorder characterized by congenital defects, bone marrow (BM) failure and predisposition to leukemia. The progressive aplastic anemia suggests a defect in the ability of hematopoietic stem cells (HSC) to sustain hematopoieis. We have examined the role of the nuclear FA core complex gene Fancg in the functionality of HSC. In Fancg-/- mice, we observed a decay of long-term HSC and multipotent progenitors that account for the reduction in the LSK compartment containing primitive hematopoietic cells. Fancg-/- lymphoid and myeloid progenitor cells were also affected, and myeloid progenitors show compromised in vitro functionality. HSC from Fancg-/- mice failed to engraft and to reconstitute at short and long term the hematopoiesis in a competitive transplantation assay. Fancg-/- LSK cells showed a loss of quiescence, an impaired migration in vitro in response to the chemokine CXCL12 and a defective homing to the BM after transplantation. Finally, the expression of several key genes involved in self-renewal, quiescence and migration of HSC was dysregulated in Fancg-deficient LSK subset. Collectively, our data reveal that Fancg should play a role in the regulation of physiological functions of HSC.

Impaired mesenchymal stem cell differentiation and osteoclastogenesis in mice deficient for Igf2-P2 transcripts.

During embryonic development, Igf2 gene transcription is highly regulated through the use of several promoters whose specific roles are not defined. Here, we show that loss-of-function of one of these promoters, Igf2-P2, results in growth defects that are temporally and quantitatively different from those seen in Igf2-null mutants. In particular, Igf2-P2 mutants exhibit skeletal abnormalities characterized by thin and short bones with reduced mineralization and medullar cavity and with altered bone remodeling. These abnormalities are associated with decreased numbers of embryonic mesenchymal chondroprogenitors, adult mesenchymal stem cells and osteoprogenitors. Differentiation of osteoprogenitors into osteoblasts is impaired in the Igf2-P2 mutant mice in a cell-autonomous manner, and osteopontin is a target of the IGF2 signaling pathway during this differentiation. Igf2-P2 mutant mice also display impaired formation of giant osteoclasts owing to a defective micro-environment. These results support a model wherein transcriptional activity of the Igf2-P2 promoter regulates the fate of mesenchymal progenitors during bone development and remodeling in the adult, and regulates osteogenesis in a cell-autonomous and non-autonomous manner.

Analysis of factors associated with patient-reported outcome (PRO) score completion rate one year after shoulder surgeries.

Background: Patient-reported outcome measurements (PROMs) are important metrics for monitoring improvements following shoulder surgery. Despite the easy accessibility of electronic PROM surveys, completion rates vary, and factors predictive of survey completion for patients enrolled in medical survey follow-up after shoulder surgery remain largely unknown. The purpose of this study is to investigate survey completion rates for common shoulder procedures and identify factors predictive of PROM completion at one-year postoperatively. We hypothesize that the response rate to shoulder PROMs may vary by the shoulder procedure type after surgery. Methods: Patients undergoing total shoulder arthroplasty (TSA), rotator cuff repair (RCR), and instability surgery (Latarjet procedure [LP], and arthroscopic Bankart repair [ABR]) from 2019 to 2021 were prospectively enrolled. Each patient was administered PROM surveys via email preoperatively and at 2-weeks, 6-weeks, 3-months, 6-months, and 12-months following surgery. Demographics and socioeconomic characteristics were collected from our institutional database. The primary outcome studied was survey completion rate by procedure. Multivariable logistic regression was performed to identify factors predictive of completing 12-month follow-up. Results: A total of 514 (251 TSA, 194 RCR, and 69 instability surgery (35 LP, 34 ABR)) patients with an average age of 58 ± 15 years were included in this study. Overall, the 12-month survey completion rate for all procedures was 57.2%. TSA had the highest completion rate (64.9%), followed by RCR (52.1%), ABR (44.2%), and LP (42.9%). ABR and LP demonstrated more than a 50% drop in survey response at 2 weeks, and the RCR cohort demonstrated an increased attrition in survey response at the 6-month mark. Patients who completed the 12-month follow-up survey were older [61 ± 14 vs. 54 ± 17; P < .001], less frequently self-identified as Hispanic [13% vs. 23%; P = .009], less frequently single [32% vs. 44%; P = .008], and most frequently classified as the American Society of Anesthesiology [ASA] score II [65%, P = .001]. Conclusion: Postoperative PROM survey completion rates vary significantly among commonly performed shoulder procedures during the first year after surgery. Hispanic ethnicity and younger age were all predictive of a lower propensity, and the TSA procedure is predictive of higher odds for PROM survey completion at the 12-month follow-up.

Clinical outcomes of open Latarjet-Patte procedures performed for recurrent anterior shoulder instability with primary bone loss versus failed arthroscopic Bankart repair.

BACKGROUND: This study compares the outcomes of Latarjet-Patte procedures (LPs) performed for primary glenohumeral instability in the setting of critical bone loss (LP-BL) versus salvage surgery performed after a failed arthroscopic Bankart repair (LP-FB). METHODS: LP's performed by senior author from 2017 to 2021 were separated into cohorts by LP indication. Data abstracted from electronic medical records included demographic information, preoperative clinical scores, radiological imaging, and complications. Postoperative clinical outcome scores collected after a 2-year minimum follow-up included: patient-reported outcomes measurement information system (PROMIS) upper extremity (UE), PROMIS pain interference, PROMIS pain intensity, American Shoulder and Elbow Surgeons (ASES), and visual analog scale pain scores. RESULTS: A total of 47 patients (LP-BL: n=29, LP-FB: n=18) with a mean age of 29 years (range, 15-58 years) were included in this study. Both cohorts achieved good upper extremity functionality without significant differences as indicated by mean PROMIS UE (LP-BL: 52.6±10.0 vs. LP-FB: 54.6±7.6, P=0.442) and ASES score (LP-BL: 89.9±15.7 vs. LP-FB: 91.5±14.4, P=0.712). However, the LP-FB cohort reported lower levels of pain (LP-FB: 0.5±1.1 vs. LP-BL: 1.9±2.7, P=0.020) at their latest follow-up. There were no significant differences in complication rates including re-dislocation between cohorts (LP-BL: 2/29 [6.9%] vs. LP-FB: 2/18 [11.1%], P=0.629). CONCLUSIONS: When performed after failed Bankart repair, the LP results in similar postoperative functional outcomes and similar rates of complications and re-dislocations when compared to the primary indication of recurrent glenohumeral instability in the setting of critical bone loss. Level of evidence: III.

Pathophysiology of sickle cell disease is mirrored by the red blood cell metabolome.

Emerging metabolomic tools can now be used to establish metabolic signatures of specialized circulating hematopoietic cells in physiologic or pathologic conditions and in human hematologic diseases. To determine metabolomes of normal and sickle cell erythrocytes, we used an extraction method of erythrocytes metabolites coupled with a liquid chromatography-mass spectrometry-based metabolite profiling method. Comparison of these 2 metabolomes identified major changes in metabolites produced by (1) endogenous glycolysis characterized by accumulation of many glycolytic intermediates; (2) endogenous glutathione and ascorbate metabolisms characterized by accumulation of ascorbate metabolism intermediates, such as diketogulonic acid and decreased levels of both glutathione and glutathione disulfide; (3) membrane turnover, such as carnitine, or membrane transport characteristics, such as amino acids; and (4) exogenous arginine and NO metabolisms, such as spermine, spermidine, or citrulline. Finally, metabolomic analysis of young and old normal red blood cells indicates metabolites whose levels are directly related to sickle cell disease. These results show the relevance of metabolic profiling for the follow-up of sickle cell patients or other red blood cell diseases and pinpoint the importance of metabolomics to further depict the pathophysiology of human hematologic diseases.

Distal Intersection Syndrome Between Second and Third Dorsal Compartments of the Wrist.

Distal intersection syndrome (DIS) is a rare form of tenosynovitis affecting the second and third dorsal extensor compartments of the wrist, which is rarer and more distal than the classically described intersection syndrome between the first and second compartments. In this report, we present three cases of DIS, their inciting activities, and ensuing treatment courses. Diagnosis of DIS was confirmed via MRI in all cases. Treatment modalities consisted of non-steroidal anti-inflammatory medications and varying durations of immobilization in all three patients, initially. One patient ultimately underwent surgical debridement and partial tenosynovectomy. At the end of follow-up, all patients saw a reduction in symptomatology with a return to baseline activity levels. This case report provides an overview of the possible clinical courses of DIS, as well as treatment strategies that can be implemented. Providers must maintain a high index of suspicion for this condition and treat patients with a great deal of caution, as extensor tendon rupture is possible.

Snapping Sternoclavicular Joint.

Snapping sternoclavicular joint (SCJ) is a rare presentation in the SCJ. We present a case report detailing the presentation and treatment of unilateral snapping SCJ in a 14-year-old male patient. Clinical findings included the subluxation of the medial end of the clavicle in the anterior-posterior direction following a specific maneuver by the patient that involved repetitive external rotation with the arm in horizontal abduction. Dynamic ultrasound demonstrated an asymmetric widening of the right sternoclavicular joint in the neutral position with a pronounced subluxation in provocative positioning. At 3.5-year follow-up, he continued to remain pain-free without static deformity of the SCJ. Snapping SCJ is a benign phenomenon that does not require any intervention and is not associated with ligament laxity.