The effect of minimally invasive sacroiliac joint fusion compared to sham operation: a double-blind randomized placebo-controlled trial.

Background: Minimally invasive fusion of the sacroiliac joint as treatment for low back pain may reduce pain and improve function compared to non-operative treatment, although clear evidence is lacking. The aim of this trial was to evaluate the effect of minimally invasive sacroiliac joint fusion compared to sham surgery on sacroiliac joint pain reduction. Methods: In this double-blind randomized sham surgery-controlled trial patients with clinical diagnosis of sacroiliac joint pain confirmed with sacroiliac joint injection were included at two university hospitals in Sweden and Norway. Patients were randomized by the operating surgeon at each site to minimally invasive sacroiliac joint fusion or sham surgery. The primary endpoint was group difference in sacroiliac joint pain on the operated side at six months postoperatively, measured by the Numeric Rating Scale (0-10). Un-blinding and primary analysis were performed when all patients had completed six months follow-up. The trial is closed for new participants and was registered at clinicaltrials.gov: NCT03507049. Findings: Between September 1st, 2018 and October 22nd, 2021, 63 patients were randomized, 32 to the surgical group, 31 to the sham group. Mean age was 45 years (range 26-63) and 59 of 63 (94%) patients were female. The mean reduction in the operated sacroiliac joint from baseline to six months postoperative was 2.6 Numeric Rating Scale points in the surgical group and 1.7 points in the sham group (mean between groups difference -1.0 points; 95% CI, -2.2 to 0.3; p = 0.13). Interpretation: This double-blind randomized controlled trial could not prove that minimally invasive fusion of the sacroiliac joint was superior to sham surgery at six months postoperative. Funding: Sophies Minde Ortopedi supported a clinical research position for Engelke Marie Randers. Region Stockholm supported the cost for the Swedish ethical application and a clinical research appointment for Paul Gerdhem.

The Inhibition of the Membrane-Bound Transcription Factor Site-1 Protease (MBTP1) Alleviates the p.Phe508del-Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Defects in Cystic Fibrosis Cells.

Cystic Fibrosis (CF) is present due to mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, the most frequent variant being p.phe508del. The CFTR protein is a chloride (Cl-) channel which is defective and almost absent of cell membranes when the p.Phe508del mutation is present. The p.Phe508del-CFTR protein is retained in the endoplasmic reticulum (ER) and together with inflammation and infection triggers the Unfolded Protein Response (UPR). During the UPR, the Activating Transcription Factor 6 (ATF6) is activated with cleavage and then decreases the expression of p.Phe508del-CFTR. We have previously shown that the inhibition of the activation of ATF6 alleviates the p.Phe508del-CFTR defects in cells overexpressing the mutated protein. In the present paper, our aim was to inhibit the cleavage of ATF6, and thus its activation in a human bronchial cell line with endogenous p.Phe508del-CFTR expression and in bronchial cells from patients, to be more relevant to CF. This was achieved by inhibiting the protease MBTP1 which is responsible for the cleavage of ATF6. We show here that this inhibition leads to increased mRNA and p.Phe508del-CFTR expression and, consequently, to increased Cl-efflux. We also explain the mechanisms linked to these increases with the modulation of genes when MBTP1 is inhibited. Indeed, RT-qPCR assays show that genes such as HSPA1B, CEBPB, VIMP, PFND2, MAPK8, XBP1, INSIG1, and CALR are modulated. In conclusion, we show that the inhibition of MBTP1 has a beneficial effect in relevant models to CF and that this is due to the modulation of genes involved in the disease.

Perioperative strategies for patients undergoing subtotal cholecystectomy: a single-center retrospective review of 102 procedures.

BACKGROUND: Calculous gall bladder disease is often handled by laparoscopic cholecystectomy. In cases where a safe dissection of the hepatocystic triangle cannot be carried out, a subtotal cholecystectomy (STC) may be performed. The perioperative management of patients undergoing STC is characterized by limited evidence. This large single-center series explores some of the perioperative aspects and outcomes after STC. MATERIALS AND METHODS: The study population includes all patients who underwent STC at Oslo University Hospital (Ullevål and Aker Hospitals) from 01.01.2014 to 30.09.2020. A STC was defined as a cholecystectomy where there was a failure to control the cystic duct during surgery. Study variables included demographic data, comorbidities, previous biliopancreatic disease, indication for surgery, perioperative information, subsequent interventions and outcome data. RESULTS: During the study period, 2376 cholecystectomies were performed, and 102 (4.3%) were categorized as STC. Of all patients with STC, 48 (47.1%) had an intra- or postoperative ERCP during the index hospital admission. The indication for ERCP was bile leak in 37 (42.6%) of the cases. The bile leak resolution rate was 60.0 % in intraoperative ERCP vs 95.7% in postoperative ERCP. Among the STC patients, there were no injuries to the central bile ducts. Later, one patient has undergone a remnant cholecystectomy, following fenestrating STC. CONCLUSION: STC was a safe bailout strategy for dissection in the hepatocystic triangle in difficult cholecystectomies. Intraoperative ERCP increased procedure time and was associated with a lower rate of leak resolution, as compared to postoperative ERCP.

New insights in the prevalence of scoliosis and musculoskeletal asymmetries in adolescents with esophageal atresia.

BACKGROUND: Increased risk of scoliosis and musculoskeletal abnormalities in adolescents with esophageal atresia (EA) is reported, but the impact of these abnormalities on physical fitness and motor skills are not known. METHODS: Scoliosis was assessed radiographically and shoulder and chest abnormalities by a standardized protocol. Physical fitness was evaluated with Grippit, Six-minute walk test, and International Physical Activity Questionnaire and motor skills by Motor Assessment Battery for Children. RESULTS: Sixty-seven EA adolescents median 16 (13-20) years participated. The prevalence of significant scoliosis (≥ 20º) was 12% (8/67) whereas 22% (15/67) had mild scoliosis (10-19º). Vertebral anomalies occurred in 18/67 (27%), eight of them (44%) had scoliosis. The majority of adolescents (15/23) with scoliosis did not have vertebral anomalies. Musculoskeletal abnormalities were detected in 22-78%. Balance problems occurred three times more frequently than expected (44% vs. 15%, p = 0.004). Submaximal exercise capacity was significantly reduced compared to reference values (p < 0.001). Scoliosis ≥ 20º was related to reduced physical activity (p = 0.008), and musculoskeletal abnormalities to reduced physical activity and impaired motor skills (p = 0.042 and p < 0.038, respectively). CONCLUSIONS: Significant scoliosis was diagnosed in 12% of the EA adolescents and related to reduced physical activity. Musculoskeletal abnormalities identified in more than half of the patients, were related to reduced physical activity and impaired motor skills, and exercise capacity was significantly below reference group. EA patients with and without vertebral anomalies need health-promoting guidance to prevent impaired motor skills and consequences of reduced physical activity. LEVEL OF EVIDENCE: Prognostic Study, Level II.

Evaluation of aminopyrrolidine amide to improve chloride transport in CFTR-defective cells.

The aminopyrrolidine amide PF-429242 is a specific inhibitor of the Site-1 Protease which is responsible for the cleavage, and thus the activation of the Activating Transcription Factor6 that down regulates many genes, during the Unfolded Protein Response. We hypothesized that PF-429242 could be used to prevent the ATF6-dependent down regulation of some genes. We chose the CFTR gene encoding the CFTR chloride channel as a model because it is down-regulated by ATF6 in Cystic Fibrosis. We evaluated the action of PF-429242 in human bronchial cells expressing the most frequent mutation of CFTR (p.Phe508del) found in patients. We observed that PF-429242 increases the synthesis of the mRNA and the protein encoded by the CFTR gene harbouring the mutation. We also observed that PF-429242 alleviates the defects of the p.Phe508del-CFTR channel in human Cystic Fibrosis cells. Our results suggest that aminopyrrolidine amide is a potential therapeutic target for Cystic Fibrosis that could also have beneficial effects in other diseases involving CFTR, such as the Chronic Obstructive Pulmonary Disease.

The effect of minimally invasive sacroiliac joint fusion compared with sham operation: study protocol of a prospective double-blinded multicenter randomized controlled trial.

Background and purpose - The sacroiliac joint is increasingly recognized as a cause of pain in 15-30% of patients with low back pain. Nonoperative management is not always successful and surgical treatment with fusion of the joint is increasingly recommended. According to the literature, minimally invasive fusion reduces pain and improves function compared with nonoperative treatment. It is, however, unclear to what extent the placebo effect influences these results. Patients and methods - The trial is designed as a prospective multi-center, double-blind, randomized shamsurgery controlled trial with 2 parallel groups. 60 patients with a suspected diagnosis of sacroiliac joint pain confirmed with sacroiliac joint injection are included according to the trial inclusion criteria. Patients are randomized with a 1:1 allocation into 2 groups of 30 patients each. The primary end-point is group difference in sacroiliac joint pain intensity on the operated side at 6 months postoperatively, measured by the Numeric Rating Scale. The main objective is to examine whether there is a difference in pain reduction between patients treated with a minimally invasive fusion of the sacroiliac joint compared with patients undergoing a sham operation. Results - Unblinding occurs after the completed 6-month follow-up. The primary analysis will be performed when all patients have completed 6 months' follow-up. Follow-ups are continued to at least 2 years postoperatively. Data from the different groups will be compared based on the "intention to treat" principle.

Reliability and Construct Validity of the Adapted Norwegian Version of the Early-Onset Scoliosis 24-item Questionnaire.

BACKGROUND: The Early-Onset Scoliosis 24-item Questionnaire (EOSQ-24) reflects issues important for patients with early-onset scoliosis (EOS) and their parents. The aim of this study was to translate the original EOSQ-24 into Norwegian and to evaluate the resulting questionnaire's reliability and construct validity. METHODS: The EOSQ-24 was translated using a forward-backward translation method, followed by an expert review. One hundred parents of a heterogenic group of patients with EOS answered the EOSQ-24 and scored Numeric Rating Scales (NRSs) to evaluate the children's general health, pain, and physical function. Two weeks later, 55 parents (55%) answered the retest questionnaire. Data quality, internal consistency, and test-retest reliability were assessed, including the minimal detectable change. Construct validity was evaluated by predefined hypotheses and correlations with NRS scores. RESULTS: There were considerable ceiling (19.0% to 63.0%) and floor effects (zero to 26.0%). The internal consistency was excellent (Cronbach α = 0.95). The minimal detectable change for the EOSQ-24 total score was 15.2 and ranged from 21.6 to 33.0 for the subdomains scores. The EOSQ-24 showed discriminate capabilities among patients with different etiology, treatment status, and severity of deformity. High correlations were found between the EOSQ-24 total score and the NRS scores for general health (r = -0.66), pain (r = -0.63), and physical function (r = -0.78). CONCLUSION: The Norwegian version of the EOSQ-24 has acceptable reliability and validity for measuring quality of life and caregiver burden among EOS children. The EOSQ-24 total score is acceptable for evaluation of these patients over time. LEVEL OF EVIDENCE: Level III, diagnostic study.

Patellar resurfacing in total knee arthroplasty: functional outcome differs with different outcome scores: A randomized, double-blind study of 129 knees with 3 years of follow-up.

BACKGROUND AND PURPOSE: Recent research on outcomes after total knee arthroplasty (TKA) has raised the question of the ability of traditional outcome measures to distinguish between treatments. We compared functional outcomes in patients undergoing TKA with and without patellar resurfacing, using the knee injury and osteoarthritis outcome score (KOOS) as the primary outcome and 3 traditional outcome measures as secondary outcomes. PATIENTS AND METHODS: 129 knees in 115 patients (mean age 70 (42-82) years; 67 female) were evaluated in this single-center, randomized, double-blind study. Data were recorded preoperatively, at 1 year, and at 3 years, and were assessed using repeated-measures mixed models. RESULTS: The mean subscores for the KOOS after surgery were statistically significantly in favor of patellar resurfacing: sport/recreation, knee-related quality of life, pain, and symptoms. No statistically significant differences between the groups were observed with the Knee Society clinical rating system, with the Oxford knee score, and with visual analog scale (VAS) for patient satisfaction. INTERPRETATION: In the present study, the KOOS--but no other outcome measure used--indicated that patellar resurfacing may be beneficial in TKA.

Intraoperative ligament laxity influences functional outcome 1 year after total knee arthroplasty.

PURPOSE: To find out if there is an association between ligament laxity measured intraoperatively and functional outcome 1 year after total knee arthroplasty (TKA). METHODS: Medial and lateral ligament laxities were measured intraoperatively in extension and in 90° of flexion in 108 patients [122 knees; median age 70 (range 42-83) years]. Mechanical axes were measured preoperatively and at 1-year follow-up. Outcome measures were the Knee Injury and Osteoarthritis Outcome Score (KOOS), the Knee Society Clinical Rating System, the Oxford Knee Score and patient satisfaction. The relationships between laxity and outcome scores were examined by median regression analyses. RESULTS: Post-operative mechanical axis had a significant effect on the association between ligament laxity and KOOS. Therefore, the material was stratified on post-operative mechanical axis. In perfectly aligned and valgus-aligned TKAs, there was a negative correlation between medial laxity and all subscores in KOOS. The most important regression coefficient (ß) was recorded for the effect of medial laxity in extension on activities of daily living (ADLs) (ß = -7.32, p < 0.001), sport/recreation (ß = -6.9, p = 0.017) and pain (ß = -5.9, p = 0.006), and for the effect of medial laxity in flexion on ADLs (ß = -3.11, p = 0.023) and sport/recreation (ß = -4.18, p = 0.042). CONCLUSIONS: In order to improve the functional results after TKA, orthopaedic surgeons should monitor ligament laxity and mechanical axis intraoperatively and avoid medial laxity more than 2 mm in extension and 3 mm in flexion in neutral and valgus-aligned knees. LEVEL OF EVIDENCE: II.

Scoliosis detection, patient characteristics, referral patterns and treatment in the absence of a screening program in Norway.

BACKGROUND: Early diagnosis of idiopathic scoliosis allows for observation and timely initiation of brace treatment in order to halt progression. School scoliosis screening programs were abolished in Norway in 1994 for lack of evidence that the programs improved outcome and for the costs involved. The consequences of this decision are discussed. OBJECTIVES: To describe the detection, patient characteristics, referral patterns and treatment of idiopathic scoliosis at a scoliosis clinic during the period 2003-2011, when there was no screening and to compare treatment modalities to the period 1976-1988 when screening was performed. METHODS: Patient demographics, age at detection, family history, clinical and radiological charts of consecutive patients referred for scoliosis evaluation during the period 2003-2011, were prospectively registered. Patients were recruited from a catchment area of about 500000 teenagers. Maturity was estimated according to Risser sign and menarcheal status. Severity of pain was recorded by a verbal 5-point scale from no pain to pain at all times. Physical and neurological examinations were conducted. The detector and patient characteristics were recorded. Referral patterns of orthopedic surgeons at local hospitals and other health care providers were recorded. Patient data was obtained by spine surgeons. Treatment modalities in the current period were compared to the period 1976-1988. RESULTS: We registered 752 patients with late onset juvenile and adolescent idiopathic scoliosis from 2003-2011. There were 644 (86%) girls and 108 (14%) boys. Mean age at detection was 14.6 (7-19) years. Sixty percent had Risser sign ≥ 3, whilst 74% were post menarche with a mean age at menarche of 13.2 years. Thirty-one percent had a family history of scoliosis. The mean major curve at first consultation at our clinic was 38° (10°-95°). About 40% had a major curve >40°. Seventy-one percent were detected by patients, close relatives, and friends. Orthopaedic surgeons referred 61% of the patients. The mean duration from detection to the first consultation was 20(0-27) months. The proportion of the average number of patients braced each year was 68% during the period with screening compared to 38% in the period without screening, while the proportion for those operated was 32% and 62%, respectively ( p=0.002, OR 3.5, (95%CI 1.6 to 7.5). CONCLUSION: In the absence of scoliosis screening, lay persons most often detect scoliosis. Many patients presented with a mean Cobb angle approaching the upper limit for brace treatment indications. The frequency of brace treatment has been reduced and surgery is increased during the recent period without screening compared with the period in the past when screening was still conducted.