Purpose Collagenase Option for Reduction of Dupuytren Long-Term Evaluation of Safety Study was a 5-year noninterventional follow-up study to determine long-term efficacy and safety of collagenase ...clostridium histolyticum (CCH) treatment for Dupuytren contracture. Methods Patients from previous CCH clinical studies were eligible. Enrolled patients were evaluated annually for contracture and safety at 2, 3, 4, and 5 years after their first injection (0.58 mg) of CCH. In successfully treated joints (≤ 5° contracture following CCH treatment), recurrence was defined as 20° or greater worsening (relative to day 30 after the last injection) with a palpable cord or any medical/surgical intervention to correct new/worsening contracture. A post hoc analysis was also conducted using a less stringent threshold (≥ 30° worsening) for comparison with criteria historically used to assess surgical treatment. Results Of 950 eligible patients, 644 enrolled (1,081 treated joints). At year 5, 47% (291 of 623) of successfully treated joints had recurrence (≥ 20° worsening)—39% (178 of 451) of metacarpophalangeal and 66% (113 of 172) of proximal interphalangeal joints. At year 5, 32% (198 of 623) of successfully treated joints had 30° or greater worsening (metacarpophalangeal 26% 119 of 451 and proximal interphalangeal 46% 79 of 172 joints). Of 105 secondary interventions performed in the successfully treated joints, 47% (49 of 105) received fasciectomy, 30% (32 of 105) received additional CCH, and 23% (24 of 105) received other interventions. One mild adverse event was attributed to CCH treatment (skin atrophy decreased ring finger circumference from thinning of Dupuytren tissue). Antibodies to clostridial type I and/or II collagenase were found in 93% of patients, but over the 5 years of follow-up, this did not correspond to any reported clinical adverse events. Conclusions Five years after successful CCH treatment, the overall recurrence rate of 47% was comparable with published recurrence rates after surgical treatments, with one reported long-term treatment-related adverse event. Collagenase clostridium histolyticum injection proved to be an effective and safe treatment for Dupuytren contracture. For those receiving treatment during follow-up, both CCH and fasciectomy were elected options. Type of study/level of evidence Therapeutic II.
In this randomized, double-blind trial involving 308 patients with Dupuytren's contractures, injections of collagenase clostridium histolyticum were more effective than placebo injections in reducing ...contractures and restoring range of motion. Adverse effects included tendon rupture in two patients and localized pain and swelling in most patients.
In patients with Dupuytren's contractures, injections of collagenase clostridium histolyticum were more effective than placebo injections in reducing contractures and restoring range of motion.
Dupuytren's disease, a progressive genetic disorder of pathologic collagen production and deposition, begins with palpable nodules in the palm.
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Later, pathologic collagen cords form, extend longitudinally, thicken, and shorten, causing flexion contractures of the joints, which can severely limit hand function. Contractures typically affect the metacarpophalangeal joint, the proximal interphalangeal joint, or both. The ring and little fingers are most commonly affected. Dupuytren's disease occurs in all racial and ethnic groups, but the incidence of this disease is highest among people of northern European descent.
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The estimated global prevalence among whites is 3 to 6%.
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Dupuytren's disease . . .
Studies comparing carpal tunnel release with ultrasound guidance (CTR-US) to mini-open CTR (mOCTR) are limited. This randomized trial compared the efficacy and safety of these techniques.
In this ...multicenter randomized trial, patients were randomized (2:1) to unilateral CTR-US or mOCTR. Outcomes included Boston Carpal Tunnel Questionnaire Symptom Severity Scale (BCTQ-SSS) and Functional Status Scale (BCTQ-FSS), numeric pain scale (0-10), EuroQoL-5 Dimension 5-Level (EQ-5D-5L), scar outcomes, and complications over 1 year.
Patients received CTR-US (n = 94) via wrist incision (mean 6 mm) or mOCTR (n = 28) via palmar incision (mean 22 mm). Comparing CTR-US with mOCTR, the mean changes in BCTQ-SSS (-1.8 versus -1.8;
= 0.96), BCTQ-FSS (-1.0 versus -1.0;
= 0.75), numeric pain scale (-3.9 versus -3.8;
= 0.74), and EQ-5D-5L (0.13 versus 0.12;
= 0.79) over 1 year were comparable between groups. Freedom from scar sensitivity or pain favored CTR-US (95% versus 74%;
= 0.005). Complications occurred in 2.1% versus 3.6% of patients (
= 0.55), all within 3 weeks postprocedure. There was one revision surgery in the CTR-US group, and no revisions for persistent or recurrent symptoms in either group.
CTR-US and mOCTR demonstrated similar improvement in carpal tunnel syndrome symptoms and quality of life with comparable low complication rates over 1 year of follow-up. CTR-US was performed with a smaller incision and associated with less scar discomfort.
Purpose To evaluate long-term efficacy and safety of collagenase clostridium histolyticum (CCH) after the third year of a 5-year nontreatment follow-up study, Collagenase Option for Reduction of ...Dupuytren Long-Term Evaluation of Safety Study. Methods This study enrolled Dupuytren contracture patients from 5 previous clinical studies. Beginning 2 years after their first CCH injection, we re-evaluated patients annually for joint contracture and safety. Recurrence in a previously successfully treated joint (success = 0° to 5° contracture after CCH administration) was defined as 20° or greater worsening in contracture in the presence of a palpable cord or medical/surgical intervention to correct new or worsening contracture. We assessed partially corrected joints (joints reduced 20° or more from baseline contracture but not to 0° to 5°) for nondurable response, also defined as 20° or greater worsening of contracture or medical/surgical intervention. Results Of 1,080 CCH-treated joints (648 metacarpophalangeal MCP; 432 proximal interphalangeal PIP; n = 643 patients), 623 (451 MCP, 172 PIP) had achieved 0° to 5° contracture in the original study. Of these joints, 35% (217 of 623) recurred (MCP 27%; PIP 56%). Of these recurrences, an intervention was performed in 7%. Of the 1,080 CCH-treated joints, 301 were partially corrected in the original study. Of these, 50% (150 of 301; MCP: 38% 57 of 152; PIP: 62% 93 of 149) had nondurable response. We identified no new long-term or serious adverse events attributed to CCH during follow-up. Anti-clostridial type I collagenase and/or anti-clostridial type II collagenase antibodies were reported for 96% or more of patients who received 2 or more CCH injections and 82% who received 1 injection. Conclusions The recurrence rate, which is comparable to other standard treatments, and the absence of long-term adverse events 3 years after initial treatment indicate that CCH is an effective and safe treatment for Dupuytren contracture. Most successfully treated joints had a contracture well below the threshold for surgical intervention 3 years after treatment. Recurrence rates among successfully treated joints were lower than nondurable response rates among partially corrected joints. Type of study/level of evidence Therapeutic IV.
Limited data are available on the efficacy of cortisone injections for glenohumeral osteoarthritis (GHOA). The amount and longevity of pain relief provided by a single cortisone injection are ...unclear. Additionally, it remains uncertain how the severity of radiographic GHOA and patient-reported function and pain levels impact the efficacy of an injection. Therefore, we sought to describe the relief provided by a single, image-guided glenohumeral injection in patients with GHOA. We hypothesized that patients with more severe radiographic GHOA and poorer baseline shoulder function would require earlier secondary intervention.
Patients with symptomatic GHOA who elected to receive a corticosteroid injection for pain relief were prospectively enrolled. A phone interview was conducted to record the baseline Oxford Shoulder Score (OSS) and visual analog scale (VAS) score prior to the injection, as well as the OSS and VAS score at months 1, 2, 3, 4, 6, 9, and 12 after the injection. The endpoint of the study occurred when patients required a second injection, progressed to surgery, or reached month 12. Patients were grouped by their respective baseline OSS (mild vs. moderate or severe) and Samilson-Prieto radiographic classification (mild, moderate, or severe) for analysis.
We analyzed 30 shoulders (29 patients). Of the patients, 52% were men. The average age was 66.1 years. No significant difference in overall survival (defined as no additional intervention) was seen between groups based on either the OSS or Samilson-Prieto grade. Additionally, the OSS and VAS score at each follow-up were compared with baseline values. For the entire cohort, a clinically significant difference was seen between baseline and months 1-4 for the OSS and between baseline and months 1-4, 6, 9, and 12 for the VAS score.
This study aimed to determine the efficacy of corticosteroid injections for GHOA. There were no differences in the need for secondary intervention in this population based on the severity of either the OSS or the Samilson-Prieto radiographic classification. However, patients with more severe shoulder dysfunction based on the OSS did experience statistically significantly greater symptomatic relief than patients with milder dysfunction. Additionally, following a single injection, patients in this cohort experienced statistically and clinically relevant improvements in shoulder function and pain up to 4 months after injection.
Comparative studies of carpal tunnel release with ultrasound guidance (CTR-US) vs. mini-open CTR (mOCTR) are limited, prompting development of this randomized trial to compare efficacy and safety of ...these techniques.
Patients were randomized (2:1) to CTR-US or mOCTR, treated by experienced hand surgeons (median previous cases: 12 CTR-US; 1000 mOCTR), and followed for 3 months.
Among 149 randomized patients, 122 received CTR-US (n = 94) or mOCTR (n = 28). Mean incision length was 6 ± 2 mm in the wrist (CTR-US) vs. 22 ± 7 mm in the palm (mOCTR) (p < 0.001). Median time to return to daily activities (2 vs. 2 days; p = 0.81) and work (3 vs. 4 days; p = 0.61) were similar. Both groups reported statistically significant and clinically important improvements in Boston Carpal Tunnel Questionnaire Symptom Severity and Functional Status Scales, Numeric Pain Scale, and EuroQoL-5 Dimension 5-Level, with no statistical differences between groups. Freedom from wound sensitivity and pain favored CTR-US (61.1% vs. 17.9%; p < 0.001). Adverse event rates were low in each group (2.1% vs. 3.6%; p = 0.55).
The efficacy and safety of CTR-US were comparable to mOCTR despite less previous surgical experience with CTR-US. The choice of CTR technique should be determined by shared decision-making between patient and physician.
www.clinicaltrials.gov
identifier is NCT05405218.
Many evolutionarily distant pathogenic organisms have evolved similar survival strategies to evade the immune responses of their hosts. These include antigenic variation, through which an infecting ...organism prevents clearance by periodically altering the identity of proteins that are visible to the immune system of the host
. Antigenic variation requires large reservoirs of immunologically diverse antigen genes, which are often generated through homologous recombination, as well as mechanisms to ensure the expression of one or very few antigens at any given time. Both homologous recombination and gene expression are affected by three-dimensional genome architecture and local DNA accessibility
. Factors that link three-dimensional genome architecture, local chromatin conformation and antigenic variation have, to our knowledge, not yet been identified in any organism. One of the major obstacles to studying the role of genome architecture in antigenic variation has been the highly repetitive nature and heterozygosity of antigen-gene arrays, which has precluded complete genome assembly in many pathogens. Here we report the de novo haplotype-specific assembly and scaffolding of the long antigen-gene arrays of the model protozoan parasite Trypanosoma brucei, using long-read sequencing technology and conserved features of chromosome folding
. Genome-wide chromosome conformation capture (Hi-C) reveals a distinct partitioning of the genome, with antigen-encoding subtelomeric regions that are folded into distinct, highly compact compartments. In addition, we performed a range of analyses-Hi-C, fluorescence in situ hybridization, assays for transposase-accessible chromatin using sequencing and single-cell RNA sequencing-that showed that deletion of the histone variants H3.V and H4.V increases antigen-gene clustering, DNA accessibility across sites of antigen expression and switching of the expressed antigen isoform, via homologous recombination. Our analyses identify histone variants as a molecular link between global genome architecture, local chromatin conformation and antigenic variation.
Background:
Carpal tunnel release (CTR) is a surgical treatment option for patients with carpal tunnel syndrome (CTS) symptoms that are unresponsive to conservative treatment. Most patients ...experience symptomatic relief after CTR regardless of the surgical technique. However, direct comparisons of the safety and effectiveness between CTR surgical techniques are limited. The purpose of this randomized controlled trial is to compare the safety and effectiveness of CTR with ultrasound guidance (CTR-US) versus mini-open CTR (mOCTR) in subjects with symptomatic CTS.
Design and methods:
TUTOR (Trial of Ultrasound guided CTR versus Traditional Open Release) is a randomized controlled trial in which 120 subjects at up to 12 sites in the United States will be randomized (2:1) to receive CTR-US or mOCTR. The primary endpoint of the study is the percentage of patients who return to normal daily activities within 3 days of the procedure. Secondary endpoints of the study are median time to return to normal daily activities, percentage of patients who return to work within 3 days of the procedure, median time to return to work, Boston Carpal Tunnel Questionnaire Symptom Severity Scale (BCTQ-SSS) change score at 3 months, BCTQ Functional Status Scale (BCTQ-FSS) change score at 3 months, Numeric Pain Scale change score at 3 months, EuroQoL-5 Dimension 5-Level (EQ-5D-5L) change score at 3 months, and the incidence of device- or procedure-related adverse events at 3 months. Patient follow-up in this trial will continue for 1 year.
Ethics and dissemination:
This study was approved by a central institutional review board and ongoing trial oversight will be provided by a data safety monitoring board (DSMB). The authors intend to report the results of this trial at medical conferences and peer-reviewed journals. The outcomes of TUTOR will have important clinical and economic implications for all stakeholders involved in treating patients with CTS.
Study registration:
ClinicalTrials.gov (https://clinicaltrials.gov): NCT05405218.
Level of evidence:
1
The diagnosis of amyloidosis is important for early intervention, disease monitoring, and prevention of complications and progression. Carpal tunnel syndrome (CTS) and trigger digit (TD) are two ...common conditions associated with early disease. The purpose of this study was to define disease prevalence among patients with bilateral CTS and multiple TDs and assess for an increased rate of diagnosis in the presence of both.
Men older than 50 years and women older than 60 years of age diagnosed with bilateral CTS, multiple TDs, or a combination of the 2 were prospectively enrolled in our study. Tenosynovial biopsy samples taken at the time of surgery were tested for the presence of amyloid using Congo red staining. Demographic and medical covariates were also collected and analyzed for differences between amyloid-positive and -negative patients.
Fifty-six patients were enrolled in the study, and nine patients tested positive for amyloid deposition. The demographics and medical comorbidities were similar between amyloid-positive and -negative patients. Thirty patients with bilateral CTS were enrolled, and four tested positive for amyloid. For patients with multiple TDs, a total of 17 patients were enrolled, and 4 tested positive for amyloid. Among patients with multiple TDs, only men tested positive for amyloid and were, on average, younger than those who tested negative (61 and 73 years, respectively). Patients presenting with a combination of CTS and TD did not exhibit increased amyloid discovery.
Hand surgeons should consider tenosynovial biopsy in men older than 50 years and women older than 60 years presenting with either bilateral CTS or multiple TDs.
Prognostic IV.
Purpose To assess the safety and efficacy of 2 concurrent injections of collagenase clostridium histolyticum (CCH) in the same hand to treat multiple Dupuytren flexion contractures. Methods In a ...multicenter, open-label phase IIIb study, 60 patients received two 0.58-mg CCH doses injected into cords affecting 2 joints in the same hand during 1 visit, followed by finger extension approximately 24 hours later. Efficacy at postinjection day 30 (change in flexion contracture and active range of motion, patient satisfaction, physician-rated improvement, and rates of clinical success flexion contracture 5° or less) and adverse events were summarized. Results The concurrent injections were most commonly administered in cords affecting metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints on the same finger (47%) or 2 MCP joints on different fingers of the same hand (37%). Mean total (sum of the 2 treated joints) flexion contracture decreased 76%, from 87° to 24° (MCP joints: 86%; PIP joints: 66%). Mean total range of motion increased from 100° to 161°. Clinical success was 76% for MCP joints and 33% for PIP joints. Most patients were very satisfied (60%) or quite satisfied (28%) with treatment. Most investigators rated treated joints as very much improved (55%) or much improved (37%). The most common treatment-related adverse events (> 75% of patients) were contusion, pain in extremity, and edema peripheral (local edema). Most adverse events were mild to moderate in severity. Serious complications included 1 pulley rupture related to study medication and 1 flexor tendon rupture (following conclusion of the study). There were no systemic complications. Conclusions Results suggest that 2 affected joints can be effectively and safely treated with concurrent CCH injections. There was an increased incidence of some adverse events with concurrent treatment (pruritus, lymphadenopathy, blood blister, and skin laceration) compared with treatment of a single joint. High degrees of patient satisfaction and physician-rated improvement were reported. Type of study/level of evidence Therapeutic IV.
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