Citations

Abstract Despite the high incidence of COVID-19 worldwide, clinical experience with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) in inborn errors of immunity remains limited. Recent studies have shown that patients with defects in type 1 interferon (IFN)-related pathways or those with autoantibodies against type 1 IFNs develop severe COVID-19. We reported the clinical course of 22 patients with CTLA-4 insufficiency and COVID-19 and retrospectively examined autoantibodies against type 1 IFNs at baseline. Data were obtained from the patient interviews and chart reviews. Screening for anti-IFN autoantibodies was performed using a multiplex particle-based assay. Student t test, Mann Whitney, analysis of variance, or χ2 tests were used where appropriate. Twenty-two patients aged from 8 months to 54 years, with genetically confirmed CLTA-4 insufficiency, developed COVID-19 from 2020 to 2022. The most common symptoms were fever, cough, and nasal congestion, and the median duration of illness was 7.5 days. Twenty patients (91%) developed mild COVID-19 and were treated as outpatients. Two patients were hospitalized because of COVID-19 pneumonia but did not require mechanical ventilation. Ten (45%) patients were vaccinated at the time of their first COVID-19 infection. Eleven patients received outpatient treatment with monoclonal antibodies against the SARS-CoV-2 spike protein. During the study period, 17 patients were vaccinated against SARS-CoV-2, with no severe vaccine-related adverse effects. Although median anti-S titers following vaccination or infection were lower in patients receiving immunoglobulin replacement therapy (IGRT) (349 IU/dL) than in those not receiving IGRT (2594 IU/dL; P = .15); 3 of 9 patients on IGRT developed titers >2000 IU/dL. All patients tested negative for autoantibodies against IFN-α, IFN-β, and IFN-ω at baseline. Most patients with CTLA-4 insufficiency and COVID-19 had nonsevere disease, lacked autoantibodies against type 1 IFNs, and tolerated messenger RNA vaccines with few adverse effects. Whether our findings can be extrapolated to patients receiving CTLA-4-targeting checkpoint inhibitors requires further studies.

Précis: When comparing patients on systemic immunosuppressive therapy to those without, there was no difference in intraocular pressure (IOP) early after SLT; however, at 1 year following SLT, IOP was higher in the immunosuppression group compared with controls. Purpose: To determine whether patients taking systemic immunosuppressive medications have a different IOP-lowering response to selective laser trabeculoplasty (SLT) compared with a control group of patients. Methods: All patients who underwent SLT at Mayo Clinic 2017–2021 were identified. Patients on systemic immunosuppressive medications at the time of SLT were compared with control patients not receiving systemic immunosuppressive medications. The primary endpoints of this study were the percentage IOP reduction at 1 to 2, 3 to 6, and 12 months. Additional analyses included the percentage of patients who did not require additional therapy at each time point. Results: There were 108 eyes of 72 patients that underwent SLT in the immunosuppressed group and 1997 eyes of 1417 patients in the control group. There was no significant difference in age-adjusted change in IOP between groups at the first postoperative visit 1 to 2 months following SLT (−18.8±20.7% vs. −16.0±16.5%, P=0.256) or 3–6 months following SLT (−15.2±21.6% vs. −18.3±23.2%, P=0.062). However, at 12 months following SLT, the IOP reduction in the immunosuppressive therapy group was significantly less compared with the control group (−15.1±21.2% vs. −20.3±22.9%, P=0.045). There was no difference between groups in the number of additional treatments during the study intervals. Conclusion: Patients in the systemic immunosuppressive therapy group showed equivalent early IOP-lowering after SLT compared with a control group, but the treatment response was diminished at 1 year. Further studies investigating IOP regulation after SLT in immunosuppressed patients are needed.

Background Following anterior cruciate ligament (ACL) injury, many athletes that undergo surgery and 6–9 months of rehabilitation struggle to return to sport. Evidence suggests that psychological factors contribute to this failure to return-to-sport. Objective Determine the motor control relationship between thigh musculature motor unit characteristics and psychological readiness to return to sport between ACL-injured and healthy controls. Study design A longitudinal cohort study. Methods Athletes longitudinally completed the ACL Return to Sport after Injury (ACL-RSI) survey and isometric strength measures with a measurement of electromyography (EMG) of the vastus lateralis, vastus medialis, biceps femoris, and semitendinosus. A score cut-off of 61 on the ACL-RSI was used to divide ACL-injured groups. EMG was decomposed to provide each identified motor unit’s characteristics (amplitude, average firing rate, etc). Results Data demonstrated increased average firing rate for hamstrings (p<0.001), decreased average firing rate for vastus lateralis (p<0.001) and decreased motor unit size for both the quadriceps and hamstrings at return-to-sport post-ACL reconstruction compared with sex-matched and age-matched healthy controls (p<0.001). Furthermore, there were marked differences in disparate ACL-RSI scores between ACL-injured athletes. Conclusions At return to sport, ACL-injured athletes have major alterations of thigh musculature motor control, with smaller motor units used by those with low ACL-RSI scores. This study uniquely demonstrates objective thigh muscle motor unit characteristics that coincide with subjective reports of psychological readiness. This information will be important to address psychomotor complexes of injury for future rehabilitation protocols.

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease (CHD) with a likely oligogenic etiology, but our understanding of the genetic complexities and pathogenic mechanisms leading to HLHS is limited. We performed whole genome sequencing (WGS) on 183 HLHS patient-parent trios to identify candidate genes, which were functionally tested in the Drosophila heart model. Bioinformatic analysis of WGS data from an index family of a HLHS proband born to consanguineous parents prioritized 9 candidate genes with rare, predicted damaging homozygous variants. Of them, cardiac-specific knockdown (KD) of mitochondrial MICOS complex subunit dCHCHD3/6 resulted in drastically compromised heart contractility, diminished levels of sarcomeric actin and myosin, reduced cardiac ATP levels, and mitochondrial fission-fusion defects. These defects were similar to those inflicted by cardiac KD of ATP synthase subunits of the electron transport chain (ETC), consistent with the MICOS complex’s role in maintaining cristae morphology and ETC assembly. Five additional HLHS probands harbored rare, predicted damaging variants in CHCHD3 or CHCHD6 . Hypothesizing an oligogenic basis for HLHS, we tested 60 additional prioritized candidate genes from these patients for genetic interactions with CHCHD3/6 in sensitized fly hearts. Moderate KD of CHCHD3/6 in combination with Cdk12 (activator of RNA polymerase II), RNF149 ( goliath , E3 ubiquitin ligase), or SPTBN1 ( β-Spectrin, scaffolding protein) caused synergistic heart defects, suggesting the likely involvement of diverse pathways in HLHS. Further elucidation of novel candidate genes and genetic interactions of potentially disease-contributing pathways is expected to lead to a better understanding of HLHS and other CHDs.

Background and Objective: The association of non-alcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD) with intensive care unit (ICU) admissions and the need for mechanical ventilation and disease severity in COVID-19 patients. Material and Methods: A systematic literature review was conducted on the databases: Cochrane, Embase, PubMed, ScienceDirect, and the Web of Science from January 2019 to June 2022. Studies evaluating MAFLD using laboratory methods, non-invasive imaging, or liver biopsy were included. The study protocol was registered in PROSPERO (ID CRD42022313259), and PRISMA guidelines were followed. The NIH quality assessment tool was used for quality assessment. RevMan version 5.3 software was used for pooled analysis. A sensitivity analysis was performed to assess the result’s stability. Results: A total of 37,974 patients from 17 studies were assessed for the association between MAFLD and ICU admission. A total of 3396 COVID-19 patients required ICU admission: 1236 (20.41%) in the MAFLD group and 2160 (6.77%) in the non-MAFLD group. The odds ratio was 1.86 for ICU admission, p = 0.007, and a (95% CI) of [1.18–2.91]. A total of 37,166 patients from 13 studies were included in the need for invasive mechanical ventilation analysis. A total of 1676 patients required mechanical ventilation: 805 in the MAFLD group (14.20% of all MAFLD patients) and 871 patients in the non-MAFLD group (2.76% of all non-MAFLD patients). The odds ratio was 2.05, p = 0.02, and a (95% CI) of [1.12–3.74]. A total of 5286 patients from 14 studies were included in the COVID-19 disease severity analysis. Severe COVID-19 was seen in 1623 patients, with 33.17% (901/2716) of MAFLD patients and 28.09% (722/2570) of non-MAFLD patients having severe disease. The odds ratio was 1.59 for disease severity, p = 0.010, and a (95% CI) of [1.12–2.26]. Conclusions: Our meta-analysis suggests that there are significantly increased odds of ICU admissions, a need for invasive mechanical ventilation, and disease severity in MAFLD patients who acquire COVID-19.

Background: The Latarjet procedure is effective for patients with anterior glenohumeral instability with substantial glenoid bone loss due to its triple blocking effect. Indications: Indications include high-risk patients with recurrent anterior glenohumeral instability with any glenoid bone loss or low-risk patients with 15% to 30% glenoid bone loss. Technique Description: An incision is made lateral to the coracoid and the deltopectoral interval is established. The pectoralis minor is released medially off the coracoid and the coracoacromial (CA) ligament is released close to the acromion. The coracoid is cut with a right-angle saw and the inferior coracoid is decorticated with a burr. Two holes are pre-drilled in the coracoid. The subscapularis is split between the upper two-thirds and lower one-third with the arm in external rotation. The capsule is split vertically at the joint line and the humeral head is retracted. The anterior glenoid is decorticated with a burr, and a hole is drilled inferiorly. The depth is measured and added to the depth of the inferior bone block hole. A fully threaded 3.5-mm solid stainless steel screw is placed in the inferior hole. Care is taken to ensure that the lateral border of the bone block is flush with the articular margin. This is repeated for the superior hole. A 1.8-mm knotless suture anchor is placed between the screws. The repair stitch is passed through the capsule and loaded onto the anchor and tensioned. The CA ligament is laid over the capsule and repaired. The subscapularis split is repaired side to side and the wound is closed in layers. Results: High return-to-sport rates, including at the same level of play, have been observed among young competitive athletes with significant glenoid bone loss who underwent a Latarjet, with similarly favorable results in older patients. Ninety-day complication rates have been reported around 9%, 5% of which constituted graft or hardware failures. Discussion/Conclusion: The Latarjet procedure is an effective option for indicated patients with anterior glenohumeral instability and may be enhanced with solid screws, proper anatomic technique, and capsulolabral repair augmentation. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

AbstractBackgroundEvidence on the impact of obesity on catheter ablation for ventricular tachycardia (VT) is scarce.Method and ResultsWe queried the Nationwide Readmissions Database to determine the hospital outcomes and procedural complications of VT ablation among the obese and nonobese populations. Obesity was associated with a more prolonged length of stay (p < .01), higher cost of hospitalization (p < .01), and higher rates of pericardial effusion or hemopericardium (p = .05) and vascular complications (p = .05). There was no significant difference in early mortality, 30‐day readmissions, and other procedural complications.ConclusionVT ablation could be performed relatively safely among patients with obesity.