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1.
Am J Sports Med ; 52(9): 2196-2204, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39101725

ABSTRACT

BACKGROUND: It remains unclear which subset of patients with recurrent patellofemoral instability would benefit from a concomitant bony realignment procedure in addition to a medial patellofemoral ligament (MPFL) reconstruction. PURPOSE: To provide midterm results for patients who underwent an isolated MPFL reconstruction as part of an ongoing prospective trial. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Patients with recurrent patellar instability were prospectively enrolled in an institutional registry beginning in March 2014. Exclusion criteria included history of a previous surgery for patellar instability, an off-loadable (inferior/lateral) chondral defect, anterior knee pain ≥50% of their chief complaint, and a "jumping J" sign. All patients underwent primary, unilateral, isolated MPFL reconstruction regardless of their bony anatomic characteristics. Patient-reported outcome measures (PROMs), episodes of recurrent instability, and ability to return to sport were obtained annually. Radiographic measurements of baseline radiographs and MRI were obtained at baseline. RESULTS: A total of 138 patients underwent isolated MPFL reconstruction between March 2014 and December 2019. The mean radiographic measurements were tibial tubercle-trochlear groove, 15.1 ± 4.9 mm; Caton-Deschamps index, 1.14 ± 0.16; patellar trochlear index, 46.9% ± 15.1%; trochlear depth index, 2.5 ± 1.2 mm; tibial tubercle to lateral trochlear ridge, -8.4 ± 5.7 mm; and patellar tendon to lateral trochlear ridge, 5.7 ± 6.2 mm. Trochlear dysplasia, defined as a trochlear depth index <3 mm, was present in 79/125 (63%) patients. A total of 50 patients reached ≥5 years, of whom 40 (80%) completed follow-up PROMs. A total of 119 patients reached ≥2 years, of whom 89 (75%) completed follow-up PROMs. Six patients (5%) reported recurrent instability with a mean time of 2.97 years after surgery. All PROMs improved over time except for the Pediatric Functional Activity Brief Scale (Pedi-FABS), which had no change. At 2 years, the mean changes from baseline for Knee injury and Osteoarthritis Outcome Score (KOOS) Quality of Life subscale (QOL), Pedi-FABS, International Knee Documentation Committee (IKDC) score, KOOS Physical Function Short Form (PS), and Kujala score were 42.1, 0.6, 35.1, -23.5, and 32.3, respectively. All changes had P values <.001 except for Pedi-FABS, which showed no change and had P > .999. At 5 years, the mean changes from baseline for KOOS-QOL, Pedi-FABS, IKDC, KOOS-PS, and Kujala score were 42.6, -2.8, 32.6, -21.5, and 31.6, respectively. All changes had P values <.001 except for Pedi-FABS, which showed no change and had P > .453. In total, 89% of patients returned to sport with a mean of 9.1 months. CONCLUSION: Midterm outcomes for patients who underwent isolated MPFL reconstruction were favorable and were maintained at 5 years. Outcomes for the expanded cohort of patients with a minimum 2-year follow-up support previously published results.


Subject(s)
Joint Instability , Patellofemoral Joint , Patient Reported Outcome Measures , Recurrence , Humans , Male , Joint Instability/surgery , Female , Patellofemoral Joint/surgery , Prospective Studies , Young Adult , Adolescent , Adult , Tibia/surgery , Return to Sport , Patella/surgery , Ligaments, Articular/surgery
2.
Am J Sports Med ; 52(10): 2541-2546, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39101638

ABSTRACT

BACKGROUND: Patellofemoral instability is associated with chondral injuries to the patella, trochlea, and lateral femoral condyle. Although studies have demonstrated an association between patellar dislocations and chondral injuries, the influence of the number of dislocations on chondrosis is not established. PURPOSE: To elucidate the precise association between the number of patellar dislocation events and the severity of chondral injuries in a multicenter cohort study at the time of patellar stabilization procedures. STUDY DESIGN: Cross-sectional study; Level of evidence, 2. METHODS: A prospective multicenter cohort study (JUPITER [Justifying Patellar Instability Treatment by Early Results]) database was queried for cases of primary patellofemoral instability procedures from December 2016 to September 2022. Cartilage lesions were classified using the International Cartilage Repair Society (ICRS) classification system during an arthroscopic or open evaluation (direct visualization), with grades 2 to 4 considered abnormal. The number of dislocations was categorized as 1, 2-5, and >5. Categorical variables were compared with the chi-square test, and binary logistic regression was performed to identify predictors of the presence of chondral lesions. RESULTS: A total of 938 knees (mean age, 16.2 ± 3.8 years; 61.4% female) were included, with 580 (61.8%) demonstrating a chondral injury. The most affected region was the patella (n = 498 [53.1%]), followed by the lateral femoral condyle (n = 117 [12.5%]) and trochlea (n = 109 [11.6%]). There were no differences in the presence (P = .17) or grade (P = .63) of patellar lesions by the number of dislocations. Patients with >5 dislocations more frequently had trochlear chondral lesions (19.8%) compared with those with fewer dislocations (1, 7.6%; 2-5, 11.0%; P < .001). More dislocations were also associated with a higher proportion of ICRS grade 2 to 4 trochlear lesions (>5, 15.3%; 2-5, 10.0%; 1, 6.9%; P = .015). Combined patellar and trochlear lesions were also more common in those with >5 dislocations (P = .001). In multivariable regression, >5 dislocations was the only variable predictive of a trochlear lesion (odds ratio, 3.03 [95% CI, 1.65-5.58]; P < .001). CONCLUSION: This large prospective cohort study demonstrated that recurrent patellar dislocations can lead to more severe chondral damage in specific locations in the knee. More than 5 dislocations was associated with a >3-fold increase in the incidence and severity of trochlear chondral injuries. There were no differences in the presence or grade of patellar lesions by the number of dislocations. These findings should caution surgeons regarding prolonged nonoperative treatment.


Subject(s)
Cartilage, Articular , Patellar Dislocation , Humans , Patellar Dislocation/epidemiology , Female , Male , Prospective Studies , Adolescent , Cross-Sectional Studies , Young Adult , Cartilage, Articular/injuries , Patellofemoral Joint/injuries , Joint Instability/epidemiology , Femur/injuries , Patella/injuries
3.
Article in English | MEDLINE | ID: mdl-38990702

ABSTRACT

Lymphangioleiomyomatosis (LAM) is a devastating disease primarily found in women of reproductive age that leads to cystic destruction of the lungs. Recent work has shown that LAM causes immunosuppression and that checkpoint inhibitors can be used as LAM treatment. Toll-like receptor (TLR) agonists can also re-activate immunity and the TLR9 agonist, CpG-ODN, has been effective in treating lung cancer in animal models. Here we investigate the use of TLR9 agonist CpG-ODN as LAM immunotherapy in combination with checkpoint inhibitor, anti-PD1, standard of care rapamycin and determine the immune mechanisms underlying therapeutic efficacy. We used survival studies, flow cytometry, ELISA, and histology to assess immune response and survival after intranasal treatment with CpG-ODN in combination with rapamycin or anti-PD1 therapy in a mouse model of metastatic LAM. We found that local administration of CpG-ODN enhances survival in a mouse model of LAM. We found that a lower dose led to longer survival likely due to fewer local side effects but increased LAM nodule count and size compared to the higher dose. CpG-ODN treatment also reduced regulatory T cells and increased the number of Th17 helper T cells as well as cytotoxic T cells. These effects appear to be mediated in part by plasmacytoid dendritic cells (pDCs), as depletion of pDCs reduces survival and abrogates Th17 T cell response. Finally, we found that CpG-ODN treatment is effective in early stage and progressive disease and is additive with anti-PD1 therapy and rapamycin. In summary, we have found that TLR9 agonist CpG-ODN can be used as LAM immunotherapy and effectively synergizes with rapamycin and anti-PD1 therapy in LAM.

4.
Orthop J Sports Med ; 12(6): 23259671241249121, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39045351

ABSTRACT

Background: Cartilage restoration procedures for patellar cartilage defects have produced inconsistent results, and optimal management remains controversial. Particulated juvenile articular cartilage (PJAC) allograft tissue is an increasingly utilized treatment option for chondral defects, with previous studies demonstrating favorable short-term outcomes for patellar chondral defects. Purpose: To identify whether there is an association between defect fill on magnetic resonance imaging (MRI) with functional outcomes in patients with full-thickness patellar cartilage lesions treated with PJAC. Study Design: Case series; Level of evidence, 4. Methods: A retrospective review of prospectively collected data was conducted on patients treated with PJAC for a full-thickness symptomatic patellar cartilage lesion between March 2014 and August 2019. MRI was performed for all patients at 6, 12, and 24 months postoperatively. Patient-reported outcome measures (PROMs) were obtained preoperatively and at 1, 2, and >2 years postoperatively. Clinical outcome scores-including the International Knee Documentation Committee (IKDC) score, the Kujala, the Knee injury and Osteoarthritis Outcome Score-Physical Function Short Form (KOOS-PS), the Knee Injury and Osteoarthritis Outcome Score-Quality of Life (KOOS-QoL), and the Hospital for Special Surgery Pediatric Functional Activity Brief Scale (HSS Pedi-FABS)-were analyzed and evaluated for a relationship with tissue fill on MRI. Results: A total of 70 knees in 65 patients (mean age, 26.6 ± 8.1 years) were identified, of which 68 knees (97%) underwent a concomitant patellar stabilization or offloading procedure. Significant improvements were observed on all postoperative PROM scores at the 1-, 2-, and >2-year follow-up except for the Pedi-FABS, which showed no significant difference from baseline. From baseline to the 2-year follow-up, the KOOS-QoL improved from 24.7 to 62.1, the IKDC improved from 41.1 to 73.5, the KOOS-PS improved from 35.6 to 15, and the Kujala improved from 52 to 86.3. Imaging demonstrated no difference in the rate of cartilage defect fill between the 3-month (66%), 6-month (72%), 1-year (74%), and ≥2-year (69%) follow-ups. No association was observed between PROM scores and the percent fill of cartilage defect on MRI at the 1- and 2-year follow-up. Conclusion: PROM scores were significantly improved at the 2-year follow-up in patients who underwent PJAC for full-thickness patellar cartilage defects. On MRI, a cartilage defect fill of >66% was achieved by 3 months in most patients. In our sample, PROM scores were not significantly associated with the defect fill percentage at the short-term follow-up.

5.
Am J Med Sci ; 368(4): 300-310, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38897565

ABSTRACT

OBJECTIVES: Oral immune tolerance (OT) is a complex process with unknown genetic regulation. Our aim is to explore possible genetic control of OT in patients with rheumatoid arthritis (RA). METHODS: RA patients with increased interferon γ production invitro when their isolated peripheral blood mononuclear cells (PBMC) were cultured with type II bovine collagen α1 chain [α1 (II)] were enrolled in this study and were randomly assigned to the "Low dose" type II collagen (CII) group (30 µg/day for 10 weeks, followed by 50 µg/day for 10 weeks, followed by 70 µg/day for 10 weeks) or "High dose" CII group (90 µg/day for 10 weeks, followed by 110 µg/day for 10 weeks, followed by 130 µg/day for 10 weeks). Heparinized blood was obtained at baseline and after each of the 10 weeks treatment for analysis of the invitro production of IFNγ by their PBMC stimulated by α1(II) . Single nucleotide polymorphism (SNP) analysis of the responders and non-responders to oral CII was conducted using GeneChip Mapping 10 K 2.0 Array. RESULTS: The SNP A-15,737 was found to associate with the ability of CII to suppress IFNγ production by α1(CII)-stimulated RA PBMC. The potential for SNP A-15,737 to associate with the OT response for patients with another autoimmune disease [OT induced by oral type I bovine collagen (CI) in patients with diffuse cutaneous systemic sclersodid (dsSSc)] was also explored. CONCLUSIONS: The ROT1 region plays a role in the control of IFNγ production after oral dosing of auto-antigens, thereby determining if oral tolerance to that antigen will develop.


Subject(s)
Arthritis, Rheumatoid , Collagen Type II , Immune Tolerance , Humans , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/genetics , Immune Tolerance/drug effects , Female , Male , Middle Aged , Collagen Type II/immunology , Collagen Type II/administration & dosage , Adult , Interferon-gamma , Polymorphism, Single Nucleotide , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Leukocytes, Mononuclear/drug effects , Administration, Oral , Cattle , Aged , Dose-Response Relationship, Drug , Animals
6.
Cell ; 187(5): 1042-1046, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38428387

ABSTRACT

Growing evidence from archaic and early modern human genomes brings new insights to the emergence of modern humans. We recount recent information collected from ancient DNA studies that inform us about the evolutionary pathway to modern humanity. These findings point to both individual- and population-level advantages underlying modern human expansion.


Subject(s)
Biological Evolution , DNA, Ancient , Hominidae , Animals , Humans , Genome, Human , Hominidae/genetics
7.
Mol Biol Evol ; 41(4)2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38507661

ABSTRACT

Recent studies have suggested that dogs were domesticated during the Last Glacial Maximum (LGM) in Siberia, which contrasts with previous proposed domestication centers (e.g. Europe, the Middle East, and East Asia). Ancient DNA provides a powerful resource for the study of mammalian evolution and has been widely used to understand the genetic history of domestic animals. To understand the maternal genetic history of East Asian dogs, we have made a complete mitogenome dataset of 120 East Asian canids from 38 archaeological sites, including 102 newly sequenced from 12.9 to 1 ka BP (1,000 years before present). The majority (112/119, 94.12%) belonged to haplogroup A, and half of these (55/112, 49.11%) belonged to sub-haplogroup A1b. Most existing mitochondrial haplogroups were present in ancient East Asian dogs. However, mitochondrial lineages in ancient northern dogs (northeastern Eurasia and northern East Asia) were deeper and older than those in southern East Asian dogs. Results suggests that East Asian dogs originated from northeastern Eurasian populations after the LGM, dispersing in two possible directions after domestication. Western Eurasian (Europe and the Middle East) dog maternal ancestries genetically influenced East Asian dogs from approximately 4 ka BP, dramatically increasing after 3 ka BP, and afterwards largely replaced most primary maternal lineages in northern East Asia. Additionally, at least three major mitogenome sub-haplogroups of haplogroup A (A1a, A1b, and A3) reveal at least two major dispersal waves onto the Qinghai-Tibet Plateau in ancient times, indicating eastern (A1b and A3) and western (A1a) Eurasian origins.


Subject(s)
Genome, Mitochondrial , Animals , Dogs , Animals, Domestic/genetics , Asia, Eastern , DNA, Mitochondrial/genetics , Genetic Variation , Haplotypes , Mammals/genetics , Phylogeny
10.
J Clin Psychopharmacol ; 44(1): 5-8, 2024.
Article in English | MEDLINE | ID: mdl-38100775

ABSTRACT

PURPOSES/BACKGROUND: The goals of this preliminary study were to survey psychiatrists and to examine the impact of advertisements on their prescription of psychotropic medications. The study specifically looked at psychiatrists in Massachusetts and Michigan, as the authors were able to readily contact the members of their respective state psychiatric societies. METHODS/PROCEDURES: We used the survey software, Quatrics, to create an online survey that was sent via email link to the members of the Massachusetts Psychiatric Society (1400 estimated members), and the Michigan Psychiatric Society (700 estimated members). Details were obtained about how challenging it was for the psychiatrist to convince the patient that a medication was not indicated. Information regarding how the psychiatrist first heard about new medications and where they go to learn more about these medications was included in the survey. FINDINGS/RESULTS: We received 162 partial or full responses to our survey, representing a response rate of 8%. Those who were less than 10 years out of training were less likely to find it "easy" to change the minds of these patients, when compared with those more than 10 years out of training (Fisher exact test, P = 0.0396). The most frequent medication named as a response to "which medications do patients request" was Rexulti (brexpiprazole), followed by Vraylar (cariprazine), Caplyta (lumateperone), and aripiprazole. IMPLICATIONS/CONCLUSIONS: This survey points to the prevalence of psychiatrists getting requests for these advertised medications and illustrates that those with fewer years out of training may have a more difficult time redirecting patients from medications that are not indicated for their illness.


Subject(s)
Direct-to-Consumer Advertising , Humans , Michigan , Advertising , Massachusetts
11.
Chest ; 164(6): e179, 2023 12.
Article in English | MEDLINE | ID: mdl-38070969
12.
Nat Ecol Evol ; 7(12): 2160-2172, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37872416

ABSTRACT

Populations genetically related to present-day Europeans first appeared in Europe at some point after 38,000-40,000 years ago, following a cold period of severe climatic disruption. These new migrants would eventually replace the pre-existing modern human ancestries in Europe, but initial interactions between these groups are unclear due to the lack of genomic evidence from the earliest periods of the migration. Here we describe the genomes of two 36,000-37,000-year-old individuals from Buran-Kaya III in Crimea as belonging to this newer migration. Both genomes share the highest similarity to Gravettian-associated individuals found several thousand years later in southwestern Europe. These genomes also revealed that the population turnover in Europe after 40,000 years ago was accompanied by admixture with pre-existing modern human populations. European ancestry before 40,000 years ago persisted not only at Buran-Kaya III but is also found in later Gravettian-associated populations of western Europe and Mesolithic Caucasus populations.


Subject(s)
Hominidae , Animals , Humans , Infant, Newborn , Genome , Europe , Genomics
13.
Ann Oncol ; 34(10): 907-919, 2023 10.
Article in English | MEDLINE | ID: mdl-37467930

ABSTRACT

BACKGROUND: IMpower010 (NCT02486718) demonstrated significantly improved disease-free survival (DFS) with adjuvant atezolizumab versus best supportive care (BSC) following platinum-based chemotherapy in the programmed death-ligand 1 (PD-L1)-positive and all stage II-IIIA non-small-cell lung cancer (NSCLC) populations, at the DFS interim analysis. Results of the first interim analysis of overall survival (OS) are reported here. PATIENT AND METHODS: The design, participants, and primary-endpoint DFS outcomes have been reported for this phase III, open-label, 1 : 1 randomised study of atezolizumab (1200 mg q3w; 16 cycles) versus BSC after adjuvant platinum-based chemotherapy (1-4 cycles) in adults with completely resected stage IB (≥4 cm)-IIIA NSCLC (per the Union Internationale Contre le Cancer and American Joint Committee on Cancer staging system, 7th edition). Key secondary endpoints included OS in the stage IB-IIIA intent-to-treat (ITT) population and safety in randomised treated patients. The first pre-specified interim analysis of OS was conducted after 251 deaths in the ITT population. Exploratory analyses included OS by baseline PD-L1 expression level (SP263 assay). RESULTS: At a median of 45.3 months' follow-up on 18 April 2022, 127 of 507 patients (25%) in the atezolizumab arm and 124 of 498 (24.9%) in the BSC arm had died. The median OS in the ITT population was not estimable; the stratified hazard ratio (HR) was 0.995 [95% confidence interval (CI) 0.78-1.28]. The stratified OS HRs (95% CI) were 0.95 (0.74-1.24) in the stage II-IIIA (n = 882), 0.71 (0.49-1.03) in the stage II-IIIA PD-L1 tumour cell (TC) ≥1% (n = 476), and 0.43 (95% CI 0.24-0.78) in the stage II-IIIA PD-L1 TC ≥50% (n = 229) populations. Atezolizumab-related adverse event incidences remained unchanged since the previous analysis [grade 3/4 in 53 (10.7%) and grade 5 in 4 (0.8%) of 495 patients, respectively]. CONCLUSIONS: Although OS remains immature for the ITT population, these data indicate a positive trend favouring atezolizumab in PD-L1 subgroup analyses, primarily driven by the PD-L1 TC ≥50% stage II-IIIA subgroup. No new safety signals were observed after 13 months' additional follow-up. Together, these findings support the positive benefit-risk profile of adjuvant atezolizumab in this setting.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Adult , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/surgery , B7-H1 Antigen/therapeutic use , Lung Neoplasms/drug therapy , Lung Neoplasms/surgery , Treatment Outcome , Antineoplastic Combined Chemotherapy Protocols/adverse effects
14.
Korean J Ophthalmol ; 37(4): 292-298, 2023 08.
Article in English | MEDLINE | ID: mdl-37336513

ABSTRACT

PURPOSE: This study aimed to investigate the impact of delayed retinal clinical care during the COVID-19 pandemic on the severity of proliferative diabetic retinopathy (PDR) and drivers of follow-up delay. We compared disease severity and follow-up rates of PDR patients requiring vitrectomy to those managed nonsurgically, and identified factors associated with need for vitrectomy. METHODS: The study included 739 patients diagnosed with PDR between January 1, 2018, and March 4, 2021, categorized into two groups based on outcome: vitrectomy nonvitrectomy. Statistical methods such as t-tests and chi-square tests were used to analyze differences in disease severity and follow-up rates before and after COVID-19 shutdown. A multivariate regression evaluated factors leading to vitrectomy by comparing initial ETDRS (Early Treatment of Diabetic Retinopathy Study) DR staging, disease stability, DR progression, proliferative complications, appointment intervals, follow-up variance, rescheduling rate, and no-show rate. RESULTS: Of the 739 patients, 202 required vitrectomy, 537 were managed nonsurgically. The vitrectomy group had more severe or unstable disease before shutdown. The interval between patient visits preshutdown was 29.76 ± 45.11 days in the vitrectomy group and 40.23 ± 56.73 days in the nonvitrectomy group (p < 0.001). Both groups experienced a significant increase in appointment intervals after shutdown, with the vitrectomy group having a greater increase. Both groups had significantly increased rescheduling rate and minimally increased no-show rate. Patient-directed rescheduling was the main driver of appointment delays. Disease factors, such as tractional retinal detachment and higher ETDRS DR staging, increased the odds of vitrectomy, while appointment burden and follow-up variability had a minimal impact. CONCLUSIONS: Patients with more severe PDR and greater delay in appointments due to the pandemic were more likely to require vitrectomy for proliferative complications. Patient-directed rescheduling was identified as the main driver of care delays, as opposed to clinic-directed rescheduling. This study highlights the importance of maintaining regular follow-up appointments for PDR patients during pandemics.


Subject(s)
COVID-19 , Diabetes Mellitus , Diabetic Retinopathy , Humans , Diabetic Retinopathy/diagnosis , Diabetic Retinopathy/epidemiology , Diabetic Retinopathy/surgery , Vitrectomy/methods , Pandemics , COVID-19/epidemiology , COVID-19/complications , Retina
15.
NeuroRehabilitation ; 52(4): 625-640, 2023.
Article in English | MEDLINE | ID: mdl-37125567

ABSTRACT

BACKGROUND: Returning to education (RtE) after an acquired brain injury (ABI) can be stressful for children/young people (CYP) and families. While much can be done to support RtE, there has been limited exploration of the lived experience of parents/carers about what can both help and hinder the process. OBJECTIVE: The aim was to understand more about RtE from parents' perspectives to inform best practice and facilitate improvements in service delivery. METHODS: A service evaluation explored parent/carer views about the RtE process and the support received from healthcare professionals at a regional centre in the UK. Questionnaires (n = 59) were sent to parents of patients treated for an ABI in the last two years. RESULTS: 31 parents (response rate = 51%) completed the survey. Results highlight the many challenges of RtE. Thematic analysis of responses revealed six key themes: Parental mindset and growth; What do they need now?; Specialist support and information; Talk and share; Challenges of new and hidden needs; and Don't forget them! CONCLUSION: Parents offer crucial insight into the challenges of the RtE process. Their feedback highlights important factors for service development and reminds professionals of the key components of an effective return.


Subject(s)
Brain Injuries , Parents , Humans , Child , Adolescent , Caregivers , Health Personnel , Patients
16.
Chest ; 163(4): 746-748, 2023 04.
Article in English | MEDLINE | ID: mdl-37031980
17.
JBJS Case Connect ; 13(2)2023 04 01.
Article in English | MEDLINE | ID: mdl-37026795

ABSTRACT

CASE: A 29-year-old woman presented with bilateral tarsal tunnel syndrome caused by bilateral flexor digitorum accessorius longus, experiencing immediate relief of symptoms after surgical intervention through 1 year. CONCLUSION: Accessory muscles can cause compressive neuropathies in multiple areas of the body. In patients who have FDAL as the cause of their tarsal tunnel syndrome, surgeons should have a high index of suspicion of bilateral FDAL if the same patient develops similar contralateral symptoms.


Subject(s)
Tarsal Tunnel Syndrome , Female , Humans , Adult , Tarsal Tunnel Syndrome/etiology , Tarsal Tunnel Syndrome/surgery , Tarsal Tunnel Syndrome/diagnosis , Leg , Muscle, Skeletal/surgery , Foot
18.
bioRxiv ; 2023 Feb 07.
Article in English | MEDLINE | ID: mdl-36798234

ABSTRACT

Rationale: Lymphangioleiomyomatosis (LAM) is a devastating disease primarily found in women of reproductive age that leads to cancer-like cystic destruction of the lungs. Recent work has shown that LAM causes immunosuppression and that checkpoint inhibitors can be used as LAM treatment. IN lung cancer, TLR agonist, in particular TLR9 agonist CpG has been shown to be effective. Objectives: Here we investigate the use of TLR9 agonist CpG as LAM immunotherapy in combination with checkpoint inhibitor, anti-PD1 and assess induced changes in anti-LAM immunity. Methods: We used a murine model of metastatic LAM to determine survival after intranasal treatment with TLR9 agonist CpG at two doses and in combination the checkpoint inhibitor immunotherapy, anti-PD-1. We used histology and flow cytometry to assess overall inflammation as well as changes in the immune response upon treatment. Measurements and Main Results: We found that local administration of CpG enhances survival in a murine model of LAM and that a lower dose more effectively balanced the inflammation induced by CpG with the anti-LAM therapeutic benefits. We also found that CpG reduces regulatory T cell infiltration in LAM lungs and that CD4 helper T cells are skewed toward pro-inflammatory phenotypes. We also found that CpG treatment is effective in both early stage and progressive disease and that CpG is synergistic with previously tested anti-PD1 therapy. Conclusions: We have found that TLR9 agonist CpG can be used as LAM immunotherapy and effectively synergizes with anti-PD1 therapy in LAM.

19.
Am J Sports Med ; 51(1): 198-204, 2023 01.
Article in English | MEDLINE | ID: mdl-36412536

ABSTRACT

BACKGROUND: Loss of initial reduction of the acromioclavicular joint after coracoclavicular (CC) ligament reconstruction remains a challenge for various repair techniques. Previous studies using polydioxanone suture cerclage augments for CC ligament reconstruction demonstrated poor clinical and biomechanical outcomes. Tape-style sutures have recently gained popularity because of their added stiffness and strength relative to traditional sutures. These tape cerclage systems have yet to be biomechanically studied in CC ligament reconstruction. PURPOSE: To determine the efficacy of a tape cerclage system as an augment to CC ligament reconstruction. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 24 human cadaveric shoulders were utilized. These were divided into 4 repair groups: anatomic CC ligament reconstruction (ACCR), ACCR with a tape cerclage augment (ACCR + C), tendon graft sling with a cerclage augment (TGS + C), or tape cerclage sling alone (CS). The repairs underwent superior/inferior cyclic loading to evaluate for displacement. Specimens were visually inspected for cortical erosion by the tape cerclage after cyclic loading. Finally, the constructs underwent superior plane load-to-failure testing. RESULTS: Less displacement after cyclic loading was observed in the ACCR + C (mean ± SD, 0.42 ± 0.32 mm), TGS + C (0.92 ± 0.42 mm), and CS (0.93 ± 0.39 mm) groups as compared with the ACCR group (4.42 ± 3.40 mm; P = .002). ACCR + C (813.3 ± 257.5 N), TGS + C (558.0 ± 120.7 N), and CS (759.5 ± 173.7 N) demonstrated significantly greater load at failure relative to ACCR (329.2 ± 118.2 N) (P < .001). ACCR + C (60.88 ± 17.3 N/mm), TGS + C (44.97 ± 9.15 N/mm), and CS (54.52 ± 14.24 N/mm) conferred greater stiffness than ACCR (27.43 ± 6.94 N/mm) (P = .001). No cortical erosion was demonstrated in any specimen after cyclic loading. CONCLUSION: In a cadaveric model at time zero, repairs utilizing a tape cerclage system confer significantly greater load to failure and stiffness, as well as decreased displacement with cyclic loading, when compared with traditional ACCR repair. CLINICAL RELEVANCE: Tape cerclage augmentation may provide a useful augment for CC ligament reconstruction.


Subject(s)
Acromioclavicular Joint , Humans , Acromioclavicular Joint/surgery , Biomechanical Phenomena , Cadaver , Suture Techniques , Ligaments, Articular/surgery
20.
Article in English | WPRIM (Western Pacific) | ID: wpr-1002341

ABSTRACT

Purpose@#This study aimed to investigate the impact of delayed retinal clinical care during the COVID-19 pandemic on the severity of proliferative diabetic retinopathy (PDR) and drivers of follow-up delay. We compared disease severity and follow-up rates of PDR patients requiring vitrectomy to those managed nonsurgically, and identified factors associated with need for vitrectomy. @*Methods@#The study included 739 patients diagnosed with PDR between January 1, 2018, and March 4, 2021, categorized into two groups based on outcome: vitrectomy nonvitrectomy. Statistical methods such as t-tests and chi-square tests were used to analyze differences in disease severity and follow-up rates before and after COVID-19 shutdown. A multivariate regression evaluated factors leading to vitrectomy by comparing initial ETDRS (Early Treatment of Diabetic Retinopathy Study) DR staging, disease stability, DR progression, proliferative complications, appointment intervals, follow-up variance, rescheduling rate, and no-show rate. @*Results@#Of the 739 patients, 202 required vitrectomy, 537 were managed nonsurgically. The vitrectomy group had more severe or unstable disease before shutdown. The interval between patient visits preshutdown was 29.76 ± 45.11 days in the vitrectomy group and 40.23 ± 56.73 days in the nonvitrectomy group (p < 0.001). Both groups experienced a significant increase in appointment intervals after shutdown, with the vitrectomy group having a greater increase. Both groups had significantly increased rescheduling rate and minimally increased no-show rate. Patient-directed rescheduling was the main driver of appointment delays. Disease factors, such as tractional retinal detachment and higher ETDRS DR staging, increased the odds of vitrectomy, while appointment burden and follow-up variability had a minimal impact. @*Conclusions@#Patients with more severe PDR and greater delay in appointments due to the pandemic were more likely to require vitrectomy for proliferative complications. Patient-directed rescheduling was identified as the main driver of care delays, as opposed to clinic-directed rescheduling. This study highlights the importance of maintaining regular follow-up appointments for PDR patients during pandemics.

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