Citations

Background: Diagnosis of foveal triangular fibrocartilage complex (TFCC) tears remains difficult. The purpose of this study was to evaluate whether dynamic computed tomography (CT) of the distal radioulnar joint (DRUJ) has a higher sensitivity in detecting foveal tears of the TFCC when compared with magnetic resonance imaging (MRI). Methods: A database query identified all patients above the age of 18 years with suspected foveal TFCC injuries who underwent bilateral dynamic CT imaging of the DRUJ, static 3T MRI, and subsequent wrist arthroscopy. All patients had evidence of foveal tenderness on clinical examination. The imaging results were validated with wrist arthroscopy. Results: Twelve patients with a mean age of 31 years (range, 18-53 years) were identified. Eight patients were diagnosed with a complete foveal detachment of the TFCC on wrist arthroscopy. Of the 8 patients with a foveal tear on DRUJ arthroscopy, only 3 had a preoperative physical examination suggestive of DRUJ instability. Magnetic resonance imaging identified foveal injuries in 4 of these 8 patients (sensitivity, 50%), and 3 of these were identified as only partial tears. Dynamic CT identified instability of DRUJ in 6 of 8 patients (sensitivity, 75%). Seven of 8 patients had imaging findings suggestive of a foveal tear when including either MRI or CT imaging (sensitivity, 88%). Of the 4 patients with an intact foveal attachment on arthroscopy, 3 (specificity, 75%) had a stable DRUJ on CT and all 4 (specificity, 100%) had an intact foveal attachment on MRI. Conclusion: Sixty-two percent of patients with foveal tears on arthroscopy have a stable DRUJ on clinical examination. When combining MRI and dynamic CT imaging of the DRUJ, the sensitivity of detecting a foveal TFCC tear approaches 88% compared with a gold standard of wrist arthroscopy.

Abstract The Warburg effect released lactate promotes cancer progression, but the mechanisms remain unclear. Here, we found lactate activated MAPK pathway through ERK-lactylation to promote cancer progression. Moreover, we identified the GCN5 as the lactyl-transferase for ERK lactylation. Interestingly, activated ERK phosphorylated GCN5 and promoted GCN5 lactyl-transferase activity for ERK, which formed the positive feedback loop to facilitate lactate-mediated cancer progression. Mechanistically, ERK-K231 lactylation decreased the dissociation energy between ERK and MEK, due to the reduced electrostatic interaction between ERK-K231 and MEK-D217. This facilitated the dissociation of ERK from MEK kinases, which in turn induced ERK dimerization and activation. Hence, we developed a cell-penetrating peptide to specifically inhibit the ERK lactylation, and demonstrated the peptide impaired the tumor growth with KRAS-mutant. Taken together, we define a molecular mechanism that lactate accelerates cancer progression through ERK-GCN5 lactylation-phosphorylation cascade and provide a strategy to target ERK lactylation, especially for RAS-MAPK-driven cancers.

Background A growing number of meta-analyses (MA) have investigated the use of spinal cord stimulation (SCS) as a treatment modality for chronic pain. The quality of these MAs has not been assessed by validated appraisal tools. Objective To examine the methodological characteristics and quality of MAs related to the use of SCS for chronic pain syndromes. Evidence review An online literature search was conducted in Ovid MEDLINE(R), Ovid EMBASE, Ovid Cochrane Database of Systematic Reviews, and Scopus databases (January 1, 2000 through June 30, 2023) to identify MAs that investigated changes in pain intensity, opioid consumption, and/or physical function after SCS for the treatment of chronic pain. MA quality was assessed using A Measurement Tool to Assess Systematic Reviews (AMSTAR-2) critical appraisal tool. Findings Twenty-five MAs were appraised in the final analysis. Three were considered “high” quality, three “low” quality, and 19 “critically low” quality, per the AMSTAR-2 criteria. There was no association between the publication year and AMSTAR-2 overall quality (β 0.043; 95% CI −0.008 to 0.095; p=0.097). There was an association between the impact factor and AMSTAR-2 overall quality (β 0.108; 95% CI 0.044 to 0.172; p=0.002), such that studies published in journals with higher impact factors were associated with higher overall quality. There was no association between the effect size and AMSTAR-2 overall quality (β −0.168; 95% CI −0.518 to 0.183; p=0.320). According to our power analysis, three studies were adequately powered (>80%) to reject the null hypothesis, while the remaining studies were underpowered (<80%). Conclusions The study demonstrates a critically low AMSTAR-2 quality for most MAs published on the use of SCS for treating chronic pain. Future MAs should improve study quality by implementing the AMSTAR-2 checklist items. PROSPERO registration number CRD42023431155.

Purpose To assess outcomes of arthroscopic posterior capsular release among athletes for loss of terminal extension following anterior cruciate ligament (ACL) reconstruction. Methods A retrospective review of prospectively collected data was performed for patients undergoing arthroscopic posterior capsular release for knee extension loss following ACL reconstruction between January 2014 and December 2019. Procedure indications included extension loss greater than 10° at least 3 months after ACL reconstruction that was refractory to physical therapy. Patients were included if they were involved in either high school or college athletics, had complete outcomes of interest, and had at least 2 years of follow‐up. Prospectively collected outcomes included preoperative and postoperative measurement of knee extension, International Knee Documentation Committee score, Lysholm score, return to sport data, and complications. Results Eighteen athletes with minimum 2 years of follow‐up who underwent posterior capsular release following ACL reconstruction performed by a single surgeon were included in the analysis. Patients underwent surgery at an average of 16 weeks after ACL reconstruction. Knee extension improved an average of 13.8° at 2 years’ follow‐up (prerelease mean extension deficit 15.1°, postrelease mean extension deficit 1.3°, P < .005). Improvements in the International Knee Documentation Committee score averaged 21.7 at 6 months and 35.0 at 24 months, both of which were statistically significant ( P < .001). Similarly, differences in Lysholm included a significant improvement of 23.0 and 34.2 at 6 months and 2 years, respectively ( P < .001). In total, 77.8% returned to sport at an average of 9.8 months from their primary ACL surgery and 6.5 months following posterior capsular release surgery. No infections or neurovascular complications were observed. One patient required secondary release to achieve adequate extension. Conclusions For athletes with persistent knee extension loss after ACL reconstruction, knee extension was significantly improved at 2 years following arthroscopic posterior capsular release. Substantial improvements in patient‐reported outcomes also were seen. In addition, subjects demonstrated a high rate of return to sport and return to preinjury performance levels. Level of Evidence Level IV, therapeutic case series.

PURPOSE High-dose methotrexate (HDMTX) is an antineoplastic dosing strategy used to treat various cancers including primary central nervous system lymphoma. Trimethoprim-sulfamethoxazole (TMP/SMX) is commonly used for antibiotic prophylaxis against Pneumocystis pneumonia infections in this patient population. Significant drug-drug interactions between TMP/SMX and methotrexate (MTX) leading to adverse outcomes have been documented, primarily in adult patients taking MTX for rheumatologic conditions. METHODS This study is a single-center, retrospective, cohort study comparing outcomes in patients where TMP/SMX was held during HDMTX and patients who received concurrent prophylactic TMP/SMX during treatment. The primary end point was mean MTX level at 24, 48, and 72 hours. Secondary end points included rate of nonhematologic toxicity, rate of hematologic toxicity, median days to MTX clearance, and frequency of glucarpidase utilization. RESULTS In total, 248 cycles of HDMTX were analyzed from 221 individual patients. One hundred ninety-one cycles were administered without prophylactic TMP/SMX, and 57 were administered with TMP/SMX. The median MTX level at 24, 48, and 72 hours in those without versus with prophylactic TMP/SMX was 4.30 versus 4.30, 0.29 versus 0.30, and 0.14 versus 0.15, respectively. Similarly, rates of hematologic and nonhematologic toxicities did not differ significantly between groups with the exception of neutropenia; however, there was no corresponding increased rate of neutropenic fever. Only one patient received glucarpidase and had not received TMP/SMX. CONCLUSION Prophylactic TMP/SMX had minimal interaction with HDMTX and does not lead to increased time to clearance or clinically relevant toxicities. Prophylactic TMP/SMX can be safely administered with HDMTX in adult patients.

PURPOSE Improving care transitions for patients with cancer discharged from the hospital is considered an important component of quality care. Digital monitoring has the potential to better the delivery of transitional care through improved patient-provider communication and enhanced symptom management. However, remote patient monitoring (RPM) interventions have not been widely implemented for oncology patients after discharge, an innovative setting in which to apply this technology. METHODS We implemented a RPM intervention which identifies medical oncology patients at discharge, monitors their symptoms for 10 days, and intervenes as necessary to manage symptoms. We evaluated the feasibility (>50% patient engagement with symptom assessment), appropriateness (symptom alerts), and acceptability (net promoter score >0.7) of the intervention and the initial effect on acute care visits and return on investment. RESULTS During the study period, January 1, 2021, to December 31, 2022, we evaluated 2,257 medical oncology discharges representing 1,857 unique patients. We found that 65.9% of patients discharged (N = 1,489) completed at least one symptom assessment postdischarge and of them, 45.5% (n = 678) generated a severe symptom alert that we helped to manage. Patients expressed high satisfaction with the intervention with a net promoter score of 84%. In preliminary analysis of patients with GI malignancies (n = 449), we found a nonsignificant decrease in 30-day readmissions for the intervention cohort (n = 269) by 5.8% as compared with the control (n = 180; from 33.3% to 27.5%; P = .22). CONCLUSION Digital transitional care management was feasible and demonstrated that patients transitioning from the hospital to home have a substantial symptom burden. The intervention was associated with high patient satisfaction but will require further refinement and evaluation to increase its impact on 30-day readmission.

Abstract Background: While brief duration primary care appointments may improve access, they also limit the time clinicians spend evaluating painful conditions. This study aimed to evaluate whether 15-minute primary care appointments resulted in higher rates of opioid prescribing when compared to ≥30-minute appointments. Methods: We performed a retrospective cohort study using electronic health record (EHR), pharmacy, and administrative scheduling data from five primary care practices in Minnesota. Adult patients seen for acute Evaluation & Management visits between 10/1/2015 and 9/30/2017 scheduled for 15-minute appointments were propensity score matched to those scheduled for ≥30-minutes. Sub-groups were analyzed to include patients with acute and chronic pain conditions and prior opioid exposure. Multivariate logistic regression was performed to examine the effects of appointment length on the likelihood of an opioid being prescribed, adjusting for covariates including ethnicity, race, sex, marital status, and prior ED visits and hospitalizations. Results: We identified 45,471 eligible acute primary care visits during the study period with 2.7% (N=1233) of the visits scheduled for 15 minutes and 98.2% (N=44238) scheduled for 30 minutes or longer. Rates of opioid prescribing were significantly lower for opioid naive patients with acute pain scheduled in 15-minute appointments when compared to appointments of 30 minutes of longer (OR 0.55, 95% CI 0.35-0.84). There were no significant differences in opioid prescribing among other sub-groups. Conclusions: For selected indications and for selected patients, shorter duration appointments may not result in greater rates of opioid prescribing for common painful conditions.

Abstract Background: Streptococcus pneumoniae is the most common bacterial cause of community acquired pneumonia and the acute respiratory distress syndrome (ARDS). Some clinical trials have demonstrated a beneficial effect of corticosteroid therapy in community acquired pneumonia, COVID-19, and ARDS, but the mechanisms of this benefit remain unclear. The objective of this study was to investigate the effects of corticosteroids on the pulmonary biology of pneumococcal pneumonia in an observational cohort of mechanically ventilated patients and in a mouse model of bacterial pneumonia with Streptococcus pneumoniae. Methods: We studied gene expression with lower respiratory tract transcriptomes from a cohort of mechanically ventilated patients and in mice. We also carried out comprehensive physiologic, biochemical, and histological analyses in mice to identify the mechanisms of lung injury in Streptococcus pneumoniae with and without adjunctive steroid therapy. Results: Transcriptomic analysis identified pleiotropic effects of steroid therapy on the lower respiratory tract in critically ill patients with pneumococcal pneumonia, findings that were reproducible in mice. In mice with pneumonia, dexamethasone in combination with ceftriaxone reduced (1) pulmonary edema formation, (2) alveolar protein permeability, (3) proinflammatory cytokine release, (4) histopathologic lung injury score, and (5) hypoxemia but did not increase bacterial burden. Conclusions: The gene expression studies in patients and in the mice support the clinical relevance of the mouse studies, which replicate several features of pneumococcal pneumonia and steroid therapy in humans. In combination with appropriate antibiotic therapy in mice, treatment of pneumococcal pneumonia with steroid therapy reduced hypoxemia, pulmonary edema, lung permeability, and histologic criteria of lung injury, and also altered inflammatory responses at the protein and gene expression level. The results from these studies provide evidence for the mechanisms that may explain the beneficial effects of glucocorticoid therapy in patients with community acquired pneumonia from Streptococcus Pneumoniae.