A proliferative burst during preadolescence establishes the final cardiomyocyte number.

It is widely believed that perinatal cardiomyocyte terminal differentiation blocks cytokinesis, thereby causing binucleation and limiting regenerative repair after injury. This suggests that heart growth should occur entirely by cardiomyocyte hypertrophy during preadolescence when, in mice, cardiac mass increases many-fold over a few weeks. Here, we show that a thyroid hormone surge activates the IGF-1/IGF-1-R/Akt pathway on postnatal day 15 and initiates a brief but intense proliferative burst of predominantly binuclear cardiomyocytes. This proliferation increases cardiomyocyte numbers by ~40%, causing a major disparity between heart and cardiomyocyte growth. Also, the response to cardiac injury at postnatal day 15 is intermediate between that observed at postnatal days 2 and 21, further suggesting persistence of cardiomyocyte proliferative capacity beyond the perinatal period. If replicated in humans, this may allow novel regenerative therapies for heart diseases.

Functional coupling between Piezo1 and TRPM4 influences the electrical activity of HL-1 atrial myocytes.

The transient receptor potential melastatin 4 (TRPM4) channel contributes extensively to cardiac electrical activity, especially cardiomyocyte action potential formation. Mechanical stretch can induce changes in heart rate and rhythm, and the mechanosensitive channel Piezo1 is expressed in many cell types within the myocardium. Our previous study showed that TRPM4 and Piezo1 are closely co-localized in the t-tubules of ventricular cardiomyocytes and contribute to the Ca2+-dependent signalling cascade that underlies hypertrophy in response to mechanical pressure overload. However, there was no direct evidence showing that Piezo1 activation was related to TRPM4 activation in situ. In the present study, we employed the HL-1 mouse atrial myocyte-like cell line as an in vitro model to investigate whether Piezo1-TRPM4 coupling can affect action potential properties. We used the small molecule Piezo1 agonist, Yoda1, as a surrogate for mechanical stretch to activate Piezo1 and detected the action potential changes in HL-1 cells using FluoVolt, a fluorescent voltage sensitive dye. Our results demonstrate that Yoda1-induced activation of Piezo1 changes the action potential frequency in HL-1 cells. This change in action potential frequency is reduced by Piezo1 knockdown using small intefering RNA. Importantly knockdown or pharmacological inhibition of TRPM4 significantly affected the degree to which Yoda1-evoked Piezo1 activation influenced action potential frequency. Thus, the present study provides in vitro evidence of a functional coupling between Piezo1 and TRPM4 in a cardiomyocyte-like cell line. The coupling of a mechanosensitive Ca2+ permeable channel and a Ca2+-activated TRP channel probably represents a ubiquitous model for the role of TRP channels in mechanosensory transduction. KEY POINTS: The transient receptor potential melastatin 4 (TRPM4) and Piezo1 channels have been confirmed to contribute to the Ca2+-dependent signalling cascade that underlies cardiac hypertrophy in response to mechanical pressure overload. However, there was no direct evidence showing that Piezo1 activation was related to TRPM4 activation in situ. We employed the HL-1 mouse atrial myocyte-like cell line as an in vitro model to investigate the effect of Piezo1-TRPM4 coupling on cardiac electrical properties. The results show that both pharmacological and genetic inhibition of TRPM4 significantly affected the degree to which Piezo1 activation influenced action potential frequency in HL-1 cells. Our findings provide in vitro evidence of a functional coupling between Piezo1 and TRPM4 in a cardiomyocyte-like cell line. The coupling of a mechanosensitive Ca2+ permeable channel and a Ca2+-activated TRP channel probably represents a ubiquitous model for the role of TRP channels in mechanosensory transduction in various (patho)physiological processes.

Cell-free DNA test for fetal chromosomal abnormalities in multiple pregnancies.

INTRODUCTION: This study aimed to report the screening performance of cell-free DNA (cfDNA) testing for chromosomal abnormalities in twins, triplets, and vanishing twin pregnancies. MATERIAL AND METHODS: Data were obtained from pregnant women with a multiple pregnancy or a vanishing twin pregnancy at ≥10 weeks' gestation who requested self-financed cfDNA testing between May 2015 and December 2021. Those that had positive screening results had diagnostic confirmatory procedures after counseling and consent. The performance of screening of the cfDNA test was determined by calculating confirmation rate and combined false-positive rate (cFPR). RESULTS: Data from 292 women were included after exclusion of those lost to follow-up, with no-result on cfDNA testing, or had reductions. Of the 292 pregnancies, 10 (3.4%) were triplets, including no cases of trisomy 21 and trisomy 18; 249 (85.3%) were twins, including 3 cases of trisomy 21 and no cases of trisomy 18 and 13; and 33 (11.3%) were vanishing twins, including 3 cases of trisomy 21 and 1 case of trisomy 18. The median (IQR) maternal age was 34 years (31-37). For triplet pregnancies, the initial no-result rate was 10.3% (95% confidence interval [CI] 3.6-26.4), all with results after redraw. For twin pregnancies, the initial no-result rate was 12.9% (95% CI 9.6-17.0), and the no-result rate after redraw was 1.6% (95% CI 0.7-3.6). For vanishing twins, there were no cases with no-result. All triplets had low-risk cfDNA results. The confirmation rate for trisomy 21 was 100% with a FPR at 0% due to the small number of positive cases for twins. For vanishing twins, one high-risk case for trisomy 21 and the only high-risk case for trisomy 18 were confirmed with a cFPR of 8.3% (n = 2/24; 95% CI 2.3-25.9). CONCLUSIONS: cfDNA testing in twin pregnancies has sufficient screening performance for trisomy 21 but the number of affected cases for other conditions is limited to draw any meaningful conclusion. The use of cfDNA testing in triplet pregnancies and vanishing twins remains an area for further research.

Arthroscopic assisted versus open non-vascularized bone grafting in delayed union and nonunion of the scaphoid: a systematic review and meta-analysis.

BACKGROUND: Delayed union and nonunion of the scaphoid is a common complication often requiring surgical reconstruction and bone grafting. Our goal was to systematically assess the healing time and clinical outcomes following arthroscopic-assisted versus open non-vascularized bone grafting of the scaphoid. METHODS: A comprehensive search of the MEDLINE, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and Cochrane Central databases was completed from inception to September 2023. We included randomized trials and observational studies that reported outcomes following scaphoid delayed union/nonunion comparing arthroscopic-assisted vs. open non-vascularized bone grafting. Two reviewers independently extracted data and assessed the risk of bias. One investigator assessed certainty of evidence and a senior investigator confirmed the assessment. We pooled effects using random-effects models, when possible, for all outcomes reported by more than 1 study. RESULTS: Overall, 26 studies and 822 patients were included in the study. Very low certainty evidence demonstrated that arthroscopic-assisted surgery may decrease healing time compared to open surgery (weighted mean difference [WMD] -7.8 weeks; 95%CI -12.8 to -2.8). Arthroscopic bone grafting did not result in an improvement in union rate (relative risk 1.01; 95%CI 0.9 to 1.09). The pooled data in arthroscopic graft group showed mean time to union of 11.4 weeks (95%CI: 10.4 to 12.5) with union rate of 95% (95%CI 91-98%). A single comparative study reported very low certainty evidence that arthroscopy-assisted vs. open surgery may not have an effect on pain relief (MD 0 cm, 95%CI -0.4 to 0.5 on VAS 10 cm for pain) or improving function (MD -1.2, 95% CI -4.8 to 2.3 on 100 points DASH). CONCLUSION AND FUTURE DIRECTIONS: Our results suggest that arthroscopic-assisted non-vascularized bone grafting may be associated with improved average weeks to heal in comparison with open surgery for scaphoid delayed union/nonunion reconstruction with overall comparable union rates. There is insufficient evidence to assess the effects of arthroscopic-assisted reconstruction on union rate, time to union, and patient-reported outcomes in patients with other important nonunion characteristics such as established humpback deformity.

Validation of the Lift-Off Screw Technique in Patients Undergoing Corrective Osteotomy for Malunited Distal Radius Fractures.

PURPOSE: The purpose of this study was to validate the clinical accuracy of the lift-off screw (LOS) technique for volar tilt correction (VTC) in patients undergoing corrective osteotomy for dorsally angulated distal radius fracture malunions. METHODS: We conducted a retrospective review of 23 patients with dorsally angulated distal radius fracture malunions treated with corrective osteotomy using the LOS technique. The LOS equation Ls = [tan(Tc) ∗ Lp + C]/[cos(⍬s)] and standardized intraoperative fluoroscopic images were used to determine and compare the calculated and clinical VTC and final volar tilt. Correlations between the LOS length and the clinical VTC were calculated, as well as between the desired VTC and the correction accuracy. RESULTS: Preoperative volar tilt ranged from -6° to -50° (mean = -22.9° ± 10.6°). The calculated VTC was 32.7° ± 9.4°, and the clinical VTC achieved was 25.8° ± 9.3°. The difference between the clinical and calculated correction was -6.9°, with an average postoperative clinical volar tilt of 2.8° ± 5.7°, compared with a calculated volar tilt of 9.7° ± 4.4°. There was a moderately strong positive correlation between LOS screw length and clinical VTC achieved, and a moderately weak negative correlation between the desired amount of correction and the accuracy of the correction. CONCLUSIONS: The LOS technique is a reproducible method to plan the amount of sagittal plane correction during corrective osteotomy surgery for dorsally angulated distal radius fracture malunions. We demonstrate that this technique underestimates the clinical correction achieved by an average of 7°, with larger deformities experiencing greater undercorrection. Undercorrection of volar tilt during corrective osteotomy should be anticipated by surgeons and considered in future implant and cutting guide designs. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Effect of Time-To-Surgery on Distal Radius Fracture Outcomes: A Systematic Review.

PURPOSE: It remains unclear whether time-to-surgery for distal radius fractures affects clinical, functional, or radiographic outcomes or health care costs/use. This systematic review investigated the outcomes of early versus delayed surgery for closed, isolated distal radius fractures in adult patients. METHODS: A comprehensive search of MEDLINE, Embase, and CINAHL databases was completed for all original case series, observational studies, and randomized controlled trials reporting clinical outcomes of both early and delayed surgically-treated distal radius fractures from database inception to July 01, 2022. A consistent threshold of two weeks was used to define early versus delayed treatment arms. RESULTS: Nine studies, including 16 intervention arms and 1,189 patients (858 early, 331 delayed), were included. Mean age was 58 years (range, 33-76). At more than one year, the frequency-weighted mean Disabilities of the Arm, Shoulder, and Hand score was 4 in the early group (n = 208; range, 1-17) and 21 in the delayed group (n = 181; range, 4-27). Range of motion, grip strength, and radiographic outcomes were comparable. The pooled mean complication rate (7% vs 5%) and revision rate (3.6% vs 1%) were very low in both groups. CONCLUSIONS: A delay in time-to-surgery greater than two weeks for distal radius fractures may be associated with inferior patient-reported outcomes. Early surgery was associated with improved long-term Disabilities of the Arm, Shoulder, and Hand scores. On the basis of the available evidence, range of motion, grip strength, and radiographic outcomes are similar. The complication and revision rates were very low in both groups and comparable. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Standardised method for cardiomyocyte isolation and purification from individual murine neonatal, infant, and adult hearts.

Primary cardiomyocytes are invaluable for understanding postnatal heart development. However, a universal method to obtain freshly purified cardiomyocytes without using different age-dependent isolation procedures and cell culture, is lacking. Here, we report the development of a standardised method that allows rapid isolation and purification of high-quality cardiomyocytes from individual neonatal through to adult C57BL/6J murine hearts. Langendorff retrograde perfusion, which is currently limited to adult hearts, was adapted for use in neonatal and infant hearts by developing an easier in situ aortic cannulation technique. Tissue digestion conditions were optimised to achieve efficient digestion of hearts of all ages in a comparable timeframe (<14 min). This resulted in a high yield (1.56-2.2 × 106 cells/heart) and viability (~70-100%) of cardiomyocytes post-isolation. An immunomagnetic cell separation step was then applied to yield highly purified cardiomyocytes (~95%) as confirmed by immunocytochemistry, flow cytometry, and qRT-PCR. For cell type-specific studies, cardiomyocyte DNA, RNA, and protein could be extracted in sufficient yields to conduct molecular experiments. We generated transcriptomic datasets for neonatal cardiomyocytes from individual hearts, for the first time, which revealed nine sex-specific genes (FDR < 0.05) encoded on the sex chromosomes. Finally, we also developed an in situ fixation protocol that preserved the native cytoarchitecture of cardiomyocytes (~94% rod-shaped post-isolation), and used it to evaluate cell morphology during cardiomyocyte maturation, as well as capture spindle-shaped neonatal cells undergoing cytokinesis. Together, these procedures allow molecular and morphological profiling of high-quality cardiomyocytes from individual hearts of any postnatal age.

Adaptation to exercise-induced stress is not dependent on cardiomyocyte α1A-adrenergic receptors.

The 'fight or flight' response to physiological stress involves sympathetic nervous system activation, catecholamine release and adrenergic receptor stimulation. In the heart, this induces positive inotropy, previously attributed to the ß1-adrenergic receptor subtype. However, the role of the α1A-adrenergic receptor, which has been suggested to be protective in cardiac pathology, has not been investigated in the setting of physiological stress. To explore this, we developed a tamoxifen-inducible, cardiomyocyte-specific α1A-adrenergic receptor knock-down mouse model, challenged mice to four weeks of endurance swim training and assessed cardiac outcomes. With 4-OH tamoxifen treatment, expression of the α1A-adrenergic receptor was knocked down by 80-89%, without any compensatory changes in the expression of other adrenergic receptors, or changes to baseline cardiac structure and function. Swim training caused eccentric hypertrophy, regardless of genotype, demonstrated by an increase in heart weight/tibia length ratio (30% and 22% in vehicle- and tamoxifen-treated animals, respectively) and an increase in left ventricular end diastolic volume (30% and 24% in vehicle- and tamoxifen-treated animals, respectively) without any change in the wall thickness/chamber radius ratio. Consistent with physiological hypertrophy, there was no increase in fetal gene program (Myh7, Nppa, Nppb or Acta1) expression. In response to exercise-induced volume overload, stroke volume (39% and 30% in vehicle- and tamoxifen-treated animals, respectively), cardiac output/tibia length ratio (41% in vehicle-treated animals) and stroke work (61% and 33% in vehicle- and tamoxifen-treated animals, respectively) increased, regardless of genotype. These findings demonstrate that cardiomyocyte α1A-adrenergic receptors are not necessary for cardiac adaptation to endurance exercise stress and their acute ablation is not deleterious.

Impact of pharmacist-managed immune checkpoint inhibitor toxicities.

BACKGROUND: Immune checkpoint inhibitors are associated with unique autoimmune side effects that differ from traditional cytotoxic chemotherapy. Pharmacists may play an important role in providing key supportive care measures necessary to aid patients and oncologists through immune-related adverse events (irAEs). This study aims to evaluate the impact of a pharmacist-managed irAE protocol in an oncology clinic. METHODS: This study is a retrospective chart review of the implementation of a pilot irAE pharmacy protocol. Patients treated with an immune checkpoint inhibitor and subsequently identified to have dermatologic, gastrointestinal, hepatic, or thyroid toxicities and managed under the pilot irAE pharmacy protocol from 1 October 2018 to 28 February 2019 were enrolled. Study endpoints included number of pharmacist interventions and physician satisfaction. Additional endpoints included pharmacotherapy initiated, dose adjustments, and patient follow-ups. RESULTS: From 1 October 2018, to 28 February 2019, 17 patients were referred and approved by their primary oncologists for pharmacy management under the pilot irAE protocol. During the pilot period, pharmacists initiated 21 new medications for the treatment of irAEs, including thyroid hormone replacement in 7 patients (41%) and oral corticosteroids in 6 patients (35%) with a total of 28 dose adjustments. In addition, the pilot protocol included an assessment of physician satisfaction, which showed a reduced number of physician hours per month managing irAEs, increased physician confidence in irAE management, and a desire for continued pharmacist-management of irAEs. CONCLUSIONS: Oncology pharmacists had an impact on management of toxicities in our oncology clinic as indicated by the pharmacist interventions and physician satisfaction.

The Effect of Forearm Position on Wrist Joint Biomechanics.

PURPOSE: All active motion wrist joint simulators have been designed to simulate physiologic wrist motion; however, a main difference among them is the orientation of the forearm (horizontal or vertical with respect to gravity). Moreover, the effect of forearm orientation on experimental results has yet to be quantified, but it may be an important variable. Thus, the purpose of this study was to determine the effect of forearm orientation on wrist kinematics and contact mechanics. METHODS: Eight cadaveric upper limbs were cycled through a flexion-extension motion using an active motion wrist simulator. Motion trials were performed in 3 forearm orientations (gravity-neutral, gravity-flexion, and gravity-extension). A computed tomography-based joint congruency technique was used to examine radiocarpal joint contact and joint contact centroid translation in the 3 tested orientations. RESULTS: At full wrist extension and wrist flexion, radioscaphoid contact area was greatest in the gravity-extension orientation. Radiolunate contact area was similar among all 3 forearm orientations. The radioscaphoid contact centroid was consistent among the 3 tested positions with the wrist in neutral wrist position. In contrast, the radioscaphoid contact centroid translated radially in the gravity-neutral position relative to the gravity-flexion position in extreme extension. There were no differences in radiolunate centroid contact position in the 3 forearm orientations. CONCLUSIONS: This study demonstrates that forearm orientation affects contact mechanics and end-range carpal kinematics. Future biomechanical studies should report forearm orientation and discuss the implication of the forearm orientation used on the experimental results. CLINICAL RELEVANCE: This study provides evidence that the wrist joint is sensitive to forearm positions consistent with activities of daily living and rehabilitation protocols.

A Biomechanical Evaluation of the ECRL Tenodesis for Reconstruction of the Scapholunate Ligament.

PURPOSE: Reconstruction of the scapholunate ligament (SLL) in the setting of dynamic instability remains a surgical challenge, with lack of consensus on the best reconstructive procedure. Reconstruction of only the dorsal component may lead to volar gapping and abnormal wrist kinematics. This cadaveric active motion simulation study determined whether scapholunate (SL) motion, angulation, and contact are restored following open reconstruction using the extensor carpi radialis longus (ECRL) tenodesis, which reconstructs both the volar and the dorsal SLL components. METHODS: Seven fresh-frozen cadaveric upper limbs (mean age, 68 ± 10.1 years) underwent a 4-stage protocol of cyclic dart-throw motion and flexion-extension motion (utilizing an active wrist motion simulator that used tendon load/motion-controlled actuation. Scaphoid and lunate motion, relative scaphoid translation, SL angle, and dorsal-volar SL diastasis were measured with (1) wrist ligaments intact, (2) following complete sectioning of the SLL, and (3) following SL reconstruction using the ECRL tenodesis technique. RESULTS: Complete SLL sectioning resulted in a typical pattern of SL instability. Following the ECRL tenodesis, lunate extension was not corrected. Scaphoid flexion, however, was not significantly different from the native state in FEM but remained significantly flexed during dart-throw motion. Differential dorsal and volar gapping did not significantly improve following ECRL tenodesis (dorsal, 1.2-2.3 mm; volar, 1.1-1.7 mm). CONCLUSIONS: This biomechanical study demonstrates that the ECRL tenodesis did not fully restore native carpal kinematics, despite dorsal and volar SLL, and scaphotrapeziotrapezoid reconstruction. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Medial elbow exposure: an anatomic comparison of 5 approaches.

PURPOSE: Several surgical approaches to the medial elbow are described; however, it remains unclear which exposure provides the optimal view of relevant medial elbow structures. The purpose of this anatomic study was to determine the visible surface area of the coronoid process, distal humerus, and radial head through 5 approaches to the medial elbow. METHODS: Eight fresh-frozen cadaveric upper extremity specimens were dissected. Five surgical approaches were performed on each specimen. The Smith muscle-splitting approach to the ulnar collateral ligament was performed first (Smith), followed by the Hotchkiss medial "Over the top" approach (Hotchkiss), the extended medial elbow approach (EMEA), the flexor carpi ulnaris splitting approach (FCU-Split), and the Taylor and Scham approach (T&S). Bony visualization was determined using laser surface scanning (Artec Space Spider; Artec 3D). The scans were segmented using commercially available digital software (Geomagic Wrap; 3D Systems Corporation), and the surface area visualized was determined. A descriptive analysis of the joint areas visible using the medial collateral ligament (MCL) as a clinical landmark was performed. RESULTS: The EMEA visualized the highest proportion of the total elbow joint from the medial side showing 13.9 ± 6.0 cm2, or 15% ± 4% of the joint. It also provided the best visualization of the coronoid (3.2 ± 1.7 cm2 of surface area, or 26% ± 9%) and distal humerus (9.9 ± 4.3 cm2, or 15% ± 4%). The Hotchkiss approach was best at visualizing the radial head (0.8 ± 0.3 cm2, or 7% ± 3%). The EMEA, Hotchkiss, and Smith approaches showed primarily the anterior bundle of the MCL, its insertion, and the regions anterior to it, whereas the FCU-Split showed the anterior bundle of the MCL and regions both anterior and posterior to it. The T&S showed primarily the areas posterior to the anterior bundle of the MCL; the anterior regions were not visible. The FCU-Split and the T&S allowed visualization of the posterior bundle of the MCL. The intraclass correlation coefficients (ICCs) for intraobserver reliability were 0.997, 0.992, and 0.974 for the test distal humerus, test coronoid, and test radial head, respectively. The ICCs for interobserver reliability were 0.915 for the test distal humerus, 0.66 for the coronoid, and 0.583 for the radial head. CONCLUSION: The EMEA provides the most visualization of the coronoid and distal humerus, whereas the Hotchkiss showed the most radial head. However, these approaches mainly visualize structures anterior to the MCL. If exposure of structures posterior to the MCL is required, the FCU-Split and T&S approaches are more appropriate.

New Species of Closely Related Endosymbiotic Dinoflagellates in the Greater Caribbean have Niches Corresponding to Host Coral Phylogeny.

Symbiotic dinoflagellates in the genus Breviolum (formerly Symbiodinium Clade B) dominate coral communities in shallow waters across the Greater Caribbean. While some formally described species exist, mounting genetic, and ecological evidence indicate that numerous more comprise this genus, many of which are closely related. To test this, colonies of common reef-building corals were sampled across a large geographical range. Phylogenetic and population genetic markers then used to examine evolutionary divergence and delineate boundaries of genetic recombination. Three new candidate species were distinguished by fixed differences in nucleotide sequences from nuclear and chloroplast DNA. Population connectivity was evident within each lineage over thousands of kilometers, however, substantial genetic structure persisted between lineages co-occurring within sampling locations, signifying reproductive isolation. While geographically widespread with overlapping distributions, each species is ecologically distinct, exhibiting specific mutualisms with phylogenetically distinct coral hosts. Moreover, significant differences in mean cell sizes provide some morphological evidence substantiating formal species distinctions. In providing evidence that satisfies the biological, phylogenetic, ecological, and morphological species concepts, we classify and formally name Breviolum faviinorum n. sp., primarily associated with Caribbean corals belonging to the Caribbean subfamily Faviinae; B. meandrinium n. sp., associated with corals belonging to the family Meandrinidae; and B. dendrogyrum n. sp., a symbiont harbored exclusively by the threatened coral Dendrogyra cylindrus. These findings support the primary importance of niche diversification (i.e. host habitat) in the speciation of symbiotic dinoflagellates.

A meta-analysis comparing complications of anterior versus dorsal osteotomy and plating for distal radial malunions.

This systematic review and meta-analysis compare the incidences of complications, reoperations and hardware removal between anterior and dorsal plating after corrective osteotomy for dorsally angulated distal radial malunions. A total of 403 patients were included; 253 patients underwent anterior corrective osteotomy and 150 underwent dorsal corrective osteotomy. Mean follow-up was 30 months. Anterior plating was associated with fewer reoperations (9% vs. 28%), less hardware removal (3% vs. 18%) and comparable major complications (5% vs. 6%) compared to dorsal plating. The adjusted model showed a significant reduction (approximately 85%) in the odds of reoperation and hardware removal in the anterior group. There was no difference in major or minor complications between the groups. Surgeons should be fully aware of the increased risks when using dorsal plate fixation after corrective osteotomy for dorsally angulated distal radial malunions.

Partial Scapholunate Interosseous Ligament Injuries: A Systematic Review of Treatment Options.

Purpose This systematic review summarizes the existing evidence on treatment options and outcomes for partial scapholunate interosseous ligament (pSLIL) injuries. Methods A systematic electronic search of Medline, Embase, and CINAHL was performed from inception through to February 13, 2022. All primary research articles addressing the treatment of pSLIL tears were eligible for inclusion regardless of timing of surgery, surgical technique, or rehabilitation. The PRISMA Checklist guided the reporting and data abstraction. Descriptive statistics and forest plots are presented. Results A total of 14 studies with 342 patients were included for analysis. Treatments were categorized into four groups: electrothermal shrinkage (ES), arthroscopic capsuloplasty (AC), open capsulodesis (OC), and no treatment (NT). There were five studies in the ES group ( N = 69, mean age = 34.3 ± 3.3 years), three studies in the AC group ( N = 138, mean age = 32.2 ± 3.8 years), five studies in the OC group ( N = 123, mean age of 30.7 ± 7.8 years), and one study in the NT group ( N = 12, mean age = 43 years, range = 28-67 years). The average postintervention visual analog scale pain score for the ES group was 1.4 ± 0.5 (from 5.7 ± 1.8), for the AC group was 3.2 ± 1.3 (from 6.6 ± 0), for the OC group was 2.3 ± 2.1 (from 5.6 ± 1.6), and for the NT group was 3.2 (from 7.6). The wrist extension range of motion improved postoperatively for all intervention groups (ES = 66.3°-70.7°; AC = 67°-74.5°; and OC = 48.9°-63.5°), whereas it remained unchanged for the NT group (46°-45°). Grip strength also improved in all intervention groups (ES = 17.9-29.9 kg; AC = 24.0-32.2 kg; and OC = 15.8-26.6 kg), while the NT group remained unchanged (25-24 kg). The radiographic scapholunate gap improved postoperatively in all groups that reported pre- and postintervention (ES = 2.2-1.9 mm; OC = 2.5-1.8 mm) and slightly worsened in the NT group (2.5-2.7 mm). In the ES group, there were three complications (11.5%, no major complications), in the AC group there was one major complication (0.9%, complex regional pain syndrome [CRPS]), and in the OC group there were six complications (15.4%, four major complications-CRPS). Conclusion All interventional treatment options (ES, AC, and OC) provided significant improvements in patient-reported pain, range of motion, grip strength, and radiographic parameters, with low complication rates. In comparison, no improvement in range of motion or grip strength was noted in the NT group. Therefore, surgical management of pSLIL injuries is an effective and relatively safe treatment option. Further studies comparing the outcomes of specific surgical treatments are warranted to further elucidate the optimal management option for pSLIL tears. Level of Evidence Level III, systematic review of Level III-IV studies.

Transiently restricting individual amino acids protects Drosophila melanogaster against multiple stressors.

Nutrition and resilience are linked, though it is not yet clear how diet confers stress resistance or the breadth of stressors that it can protect against. We have previously shown that transiently restricting an essential amino acid can protect Drosophila melanogaster against nicotine poisoning. Here, we sought to characterize the nature of this dietary-mediated protection and determine whether it was sex, amino acid and/or nicotine specific. When we compared between sexes, we found that isoleucine deprivation increases female, but not male, nicotine resistance. Surprisingly, we found that this protection afforded to females was not replicated by dietary protein restriction and was instead specific to individual amino acid restriction. To understand whether these beneficial effects of diet were specific to nicotine or were generalizable across stressors, we pre-treated flies with amino acid restriction diets and exposed them to other types of stress. We found that some of the diets that protected against nicotine also protected against oxidative and starvation stress, and improved survival following cold shock. Interestingly, we found that a diet lacking isoleucine was the only diet to protect against all these stressors. These data point to isoleucine as a critical determinant of robustness in the face of environmental challenges.

Phosphoproteomics-directed manipulation reveals SEC22B as a hepatocellular signaling node governing metabolic actions of glucagon.

The peptide hormone glucagon is a fundamental metabolic regulator that is also being considered as a pharmacotherapeutic option for obesity and type 2 diabetes. Despite this, we know very little regarding how glucagon exerts its pleiotropic metabolic actions. Given that the liver is a chief site of action, we performed in situ time-resolved liver phosphoproteomics to reveal glucagon signaling nodes. Through pathway analysis of the thousands of phosphopeptides identified, we reveal "membrane trafficking" as a dominant signature with the vesicle trafficking protein SEC22 Homolog B (SEC22B) S137 phosphorylation being a top hit. Hepatocyte-specific loss- and gain-of-function experiments reveal that SEC22B was a key regulator of glycogen, lipid and amino acid metabolism, with SEC22B-S137 phosphorylation playing a major role in glucagon action. Mechanistically, we identify several protein binding partners of SEC22B affected by glucagon, some of which were differentially enriched with SEC22B-S137 phosphorylation. In summary, we demonstrate that phosphorylation of SEC22B is a hepatocellular signaling node mediating the metabolic actions of glucagon and provide a rich resource for future investigations on the biology of glucagon action.

Concomitant Extensor Pollicis Longus and Extensor Digitorum Longus Tendon Rupture may Complicate Surgical Reconstruction following Volar Plate Fixation of the Distal Radius: A Case Report.

Introduction: Hardware prominence is one of the major established complications following volar plating of distal radius fractures. In particular, dorsal prominence of screws is the leading risk factor associated with post-surgical extensor pollicis longus (EPL) tendon rupture. Although there are many descriptions of attritional EPL ruptures in the literature, concomitant presentation of attritional EPL and extensor digitorum communis (EDC) ruptures following volar plating of distal radius fractures are minimal. Case Report: We present a case of concomitant rupture of the EPL and occult rupture of the EDC to the index finger following volar plating of the distal radius. This was discovered intraoperatively and complicated the proposed tendon transfer reconstruction. Conclusion: Locked volar plate fixation has become the preferred technique for surgical management of distal radius fractures. The complication of multiple extensor tendon ruptures is rare but nevertheless may be encountered. We discuss strategies for diagnosis, treatment, and prevention. Surgeons should be aware of and prepared to proceed with alternative reconstructive procedures if this complication is discovered.

Crohn's disease: an update.

Crohn's disease (CD) is a chronic, relapsing and remitting inflammatory bowel disease (IBD) that is increasing in incidence and prevalence globally. Management aims to achieve endoscopic healing, symptom resolution and improvement in quality of life. Therapeutic approaches in CD vary depending on disease phenotype. Thiopurines are important in steroid-sparing maintenance therapy, while anti-tumour necrosis factor agents play a fundamental role, especially in fistulising CD. Suboptimal response to these medications may require escalation to other immunosuppressive and biologic therapies, and surgical intervention is still required in a proportion of patients. Tailoring treatment to target specific patient phenotypes, disease severity and patient wishes is becoming more feasible with the growing array of therapeutic options in CD.

Gender Representation in Major Orthopaedic Surgery Meetings: A Quantitative Analysis.

Background: Orthopaedic surgery suffers from gender disparity, and annual conferences are visible opportunities to quantify gender representation within a field. Therefore, the purpose of this manuscript was to investigate the prevalence of female speakers and moderators, and male-only panel sessions, at 10 major Orthopaedic Surgery meetings. Methods: Conference programs and details of faculty moderating or presenting in 10 Orthopaedic Surgery annual meetings in 2021 were retrieved. Conferences were selected with the aim of size and diversity in subspecialty topics and included American Association of Hip and Knee Surgeons, American Association for Hand Surgery, American Academy of Orthopaedic Surgeons, American Orthopaedic Society for Sports Medicine, Canadian Orthopaedic Association (COA), European Federation of National Associations of Orthopaedics and Traumatology, North American Spine Society, Orthopaedic Research Society (ORS), Orthopaedic Trauma Association, and Pediatric Orthopaedic Society of North America (POSNA). Primary outcomes included percentage of female chairs and speakers and percentage of male-only panels, while secondary outcomes included number of publications, number of citations, and H-indexes of faculty. Further subgroup comparisons were performed between male-only panels and non-male-only panels and female members and male members. Results: Of 207 included sessions, 121 (58.5%) were male-only panels and 150 (12.6%) of 1,188 faculty members were women. Conferences organized by the COA, ORS, and POSNA had higher percentages of female representation, while spine surgery and adult hip/knee reconstruction sessions had more than 70% male-only panels and fewer than 10% female members. There were no significant differences between male members and female members regarding years of practice; however, male members were more likely to hold the title of professor (p < 0.001). Male members and female members stratified by quartiles of publications, citations, and H-indexes, moderated or participated in similar numbers of sessions, indicating an absence of selection bias. Conclusions: There is a high prevalence of male-only panels (58.5%) and an overall lack of female representation (12.6%) in 10 major Orthopaedic Surgery meetings. Male members and female members from these conferences were found to have similar qualifications academically. Specific strategies such as the elimination of male-only panels, selecting diverse conference organizers, and forming conference equity, diversity, and inclusion committees can help achieve cultural change. Level of Evidence: Level V.