Citations

AbstractBackground & AimsHepatocellular carcinoma (HCC) is the second leading cause of cancer‐related death worldwide. Most studies addressing the epidemiology of HCC originate from developed countries. This study reports the preliminary findings of a multinational approach to characterize HCC in South America.MethodsWe evaluated 1336 HCC patients seen at 14 centres in six South American countries using a retrospective study design with participating centres completing a template chart of patient characteristics. The diagnosis of HCC was made radiographically or histologically for all cases according to institutional standards. Methodology of surveillance for each centre was following AASLD or EASL recommendations.ResultsSixty‐eight percent of individuals were male with a median age of 64 years at time of diagnosis. The most common risk factor for HCC was hepatitis C infection (HCV, 48%), followed by alcoholic cirrhosis (22%), Hepatitis B infection (HBV, 14%) and NAFLD (9%). We found that among individuals with HBV‐related HCC, 38% were diagnosed before age 50. The most commonly provided therapy was transarterial chemoembolization (35% of HCCs) with few individuals being considered for liver transplant (<20%). Only 47% of HCCs were diagnosed during surveillance, and there was no difference in age of diagnosis between those diagnosed incidentally vs by surveillance. Nonetheless, being diagnosed during surveillance was associated with improved overall survival (P = .01).ConclusionsOur study represents the largest cohort to date reporting characteristics and outcomes of HCC across South America. We found an important number of HCCs diagnosed outside of surveillance programmes, with associated increased mortality in those patients.

AbstractBackgroundPatients and clinicians do not often agree on whether a decision has been made about cancer care. This could be explained by factors related to communication quality and/or the type of decision being made.MethodsWe used a self‐developed coding scheme to code a random sample of 128 encounters in which patients and clinicians either agreed (n=64) or disagreed (n=64) that a cancer care decision was made and tested for associations between concordance and key communication behaviours. We also identified and characterized cancer care decisions by topic and level of patient involvement and looked for trends.ResultsWe identified 378 cancer care decisions across 128 encounters. Explicit decisions were most commonly made about topics wherein decision control could be easily delegated to a clear and present expert (eg either the patient or the clinician). Related to this, level of patient involvement varied significantly by decision topic. Explicit decisions were rarely made in an observable way about social, non‐clinical or self‐management related topics, although patients and clinicians both reported having made a cancer care decision in encounters where no decisions were observed. We found no association between communication behaviours and concordance in our sample.ConclusionsWhat counts as a “decision” in cancer care may be constructed within disparate social roles that leave many agendas unaddressed and decisions unmade. Changing the content of conversations to encourage explicit decisions about self‐management and life context‐related topics may have greater value in enabling shared understanding than promoting communication behaviours among already high‐performing communicators.

Abstract Background GNE myopathy is a rare genetic disease characterized by progressive muscle atrophy and weakness. It is caused by biallelic mutations in the GNE gene that encodes for the bifunctional enzyme, uridine diphosphate ( UDP )‐N‐acetylglucosamine (Glc NA c) 2‐epimerase/N‐acetylmannosamine (Man NA c) kinase. Typical characteristics of GNE myopathy include progressive myopathy, first involving anterior tibialis muscle and sparing the quadriceps, and rimmed vacuoles on muscle biopsy. Identifying biallelic mutations by sequencing of the GNE gene confirms the diagnosis of GNE myopathy. In a subset of patients, diagnostic confirmation is challenged by the identification of mutations in only one allele, suggesting mutations in deep intronic regions or regulatory regions. Methods We performed targeted sequencing and copy number variant ( CNV ) analysis of GNE in two siblings who clinically presented with GNE myopathy. Further molecular and biochemical studies were done to characterize the effect of a previously uncharacterized GNE mutation. Results We report two siblings of Indian descent with characteristic features of GNE myopathy, including progressive skeletal muscle weakness initially involving the anterior tibialis, and rimmed vacuoles on muscle biopsy, in which a heterozygous mutation, p.Val727Met, was identified in both affected siblings, but no other deleterious variants in either coding region or exon–intron boundaries of the gene. Subsequent insertion/deletion analysis identified a novel 11.3‐kb deletion (Chr9 [ GRC h37]: g.36257583_36268910del) encompassing the GNE promoter region, with breakpoints residing in Alu repeats. Gene expression analysis revealed reduced GNE mRNA and protein levels, confirming decreased expression of the deleted allele harboring the deletion. Conclusions We have identified GNE as one of the genes susceptible to Alu ‐mediated recombination. Our findings suggest that the deletion may encompass the promoter or another region necessary for GNE expression. In patients with typical manifestations of GNE myopathy and a single GNE variant identified, copy number variant ( CNV ) analysis may be useful in arriving at the diagnosis.

Purpose To determine the rate of return of young amateur athletes to sport after hip arthroscopy, their clinical outcomes, and pathologic risk factors for worse outcomes 2 years after surgery. Methods This study included all patients between age 13 and 23 who participated in a sport prior to surgery with intent to return who underwent hip arthroscopy after failure of comprehensive nonoperative management for whom 2‐year outcome scores were available. Outcomes collected retrospectively included modified Harris Hip Score (mHHS) and the Hip Outcome Scores (HOS) subscales for activities of daily living (ADL) and sport (HOS Sport). In addition, sport played, return to sport rates, and Tegner Scores were measured preinjury and postoperatively. Descriptive statistics were used to present demographic data. A priori analysis was used to determine the sample size needed to show minimal clinically important differences for mHHS, HOS ADL, and HOS Sport. Results The study population included 50 patients with a mean age of 17.8 years. Athletes returned to sport at a rate of 92% (46/50). At a mean follow‐up of 34 months, the mean mHHS, HOS ADL, and HOS Sport outcome scores were 85, 91, and 80 for the entire study group; 87, 92, and 84 for the group that returned to sport; and 67, 82, and 41 for the group that did not return to sport, respectively. Median preinjury and postoperative Tegner levels were 8 and 7, respectively. Labral takedown and reattachment was associated with lower HOS ADL ( P = .01) and HOS Sport scores ( P = .02). Conclusions Athletes returned to sport at a high rate (92%; 46/50) after hip arthroscopy and perform activities at near preinjury levels. In this group of athletes, arthroscopic labral repair with chondrolabral preservation, which reflected less severe chondrolabral pathology, performed better than labral repair with takedown and reattachment. Level of Evidence Level IV, therapeutic case series.

Abstract Introduction Multiple intravenous doses of ponezumab, an anti‐amyloid antibody, were evaluated in subjects with mild‐to‐moderate Alzheimer's disease (AD). Methods In part A, 77 subjects were randomized to ponezumab 0.1, 0.5, or 1 mg/kg (75 treated) and 26 to placebo (24 treated). In part B, 63 subjects were randomized and treated with ponezumab 3 or 8.5 mg/kg and 32 with placebo. Subjects received 10 infusions over 18 months and were followed for 6 months thereafter. Results Ponezumab was generally safe and well tolerated. Most common adverse events were fall (16.7% ponezumab, 21.4% placebo), headache (13.8%, 21.4%), and cerebral microhemorrhage (13.8%, 19.6%). Plasma ponezumab increased dose‐dependently with limited accumulation. Cerebrospinal fluid penetration was low. Plasma Aβ 1–x and Aβ 1–40 showed robust increases, but cerebrospinal fluid biomarkers showed no dose response. Ponezumab had no effects on cognitive/functional outcomes or brain volume. Conclusions Multiple‐dose ponezumab was generally safe, but not efficacious, in mild‐to‐moderate AD.

Overuse of medical services is an increasingly recognized driver of poor‐quality care and high cost. A practical framework is needed to guide clinical decisions and facilitate concrete actions that can reduce overuse and improve care. We used an iterative, expert‐informed, evidence‐based process to develop a framework for conceptualizing interventions to reduce medical overuse. Given the complexity of defining and identifying overused care in nuanced clinical situations and the need to define care appropriateness in the context of an individual patient, this framework conceptualizes the patient–clinician interaction as the nexus of decisions regarding inappropriate care. This interaction is influenced by other utilization drivers, including healthcare system factors, the practice environment, the culture of professional medicine, the culture of healthcare consumption, and individual patient and clinician factors. The variable strength of the evidence supporting these domains highlights important areas for further investigation.

Background: Previous studies have reported variable rates of recurrent lateral patellar instability mainly because of limited cohort sizes. In addition, there is currently a lack of information on contralateral patellar instability. Purpose: To evaluate the rate of recurrent ipsilateral patellar dislocations and contralateral patellar dislocations after a first-time lateral patellar dislocation. Additionally, risk factors associated with recurrent dislocations (ipsilateral or contralateral) and time to recurrence were investigated. Study Design: Cohort study; Level of evidence, 3. Methods: This population-based study included 584 patients with a first-time lateral patellar dislocation occurring between 1990 and 2010. A retrospective review was conducted to gather information about the injury, subsequent dislocations (ipsilateral or contralateral), and structural characteristics including trochlear dysplasia, patella alta, and tibial tubercle to trochlear groove (TT-TG) distance. Risk factors were assessed to delineate associations with subsequent dislocations and time to recurrence. Results: At a mean follow-up of 12.4 years, 173 patients had ipsilateral recurrence, and 25 patients had a subsequent contralateral dislocation. At 20 years, the cumulative incidence of ipsilateral recurrence was 36.0%, while the cumulative incidence of contralateral dislocations was 5.4%. Trochlear dysplasia (odds ratio [OR], 18.1), patella alta (OR, 10.4), age <18 years at the time of the first dislocation (OR, 2.4), elevated TT-TG distance (OR, 2.1), and female sex (OR, 1.5) were associated with recurrent ipsilateral dislocations. Time to recurrence was significantly decreased in patients with trochlear dysplasia (23.0 months earlier time to recurrence; P < .001), elevated TT-TG distance (18.5 months; P < .001), patella alta (16.4 months; P = .001), and age <18 years at the time of the first dislocation (15.4 months; P < .001). Risk factors for subsequent contralateral dislocations included patella alta and trochlear dysplasia. Conclusion: At 20 years after a first-time lateral patellar dislocation, the cumulative incidence of recurrent ipsilateral patellar dislocations was 36.0%, compared with 5.4% for contralateral dislocations. Trochlear dysplasia, elevated TT-TG distance, patella alta, age <18 years at the time of the first dislocation, and female sex were associated with ipsilateral recurrence. Trochlear dysplasia, elevated TT-TG distance, patella alta, and age <18 years at the time of the first dislocation were predictive of a statistically significant decrease in time to recurrence.

Abstract The meniscal roots are critical in maintaining the normal shock absorbing function of the meniscus. If a meniscal root tear is left untreated, meniscal extrusion can occur rendering the meniscus nonfunctional resulting in degenerative arthritis. Two main repair techniques are described: (1) suture anchors (direct fixation) and (2) sutures pulled through a tibial tunnel (indirect fixation). Meniscal root repair using a suture anchor technique is technically challenging requiring a posterior portal and a curved suture passing device that can be difficult to manipulate within the knee. We present a technique for posterior medial meniscus root repair using 3 sutures (1 leader, 2 cinch), standard arthroscopy portals, and transtibial fixation. Overall, this technique simplifies a challenging procedure and allows for familiarity and efficiency. Technique Video video See video under supplementary data.

Study Design: Multicenter retrospective case series and review of the literature. Objective: To determine the rate of esophageal perforations following anterior cervical spine surgery. Methods: As part of an AOSpine series on rare complications, a retrospective cohort study was conducted among 21 high-volume surgical centers to identify esophageal perforations following anterior cervical spine surgery. Staff at each center abstracted data from patients’ charts and created case report forms for each event identified. Case report forms were then sent to the AOSpine North America Clinical Research Network Methodological Core for data processing and analysis. Results: The records of 9591 patients who underwent anterior cervical spine surgery were reviewed. Two (0.02%) were found to have esophageal perforations following anterior cervical spine surgery. Both cases were detected and treated in the acute postoperative period. One patient was successfully treated with primary repair and debridement. One patient underwent multiple debridement attempts and expired. Conclusions: Esophageal perforation following anterior cervical spine surgery is a relatively rare occurrence. Prompt recognition and treatment of these injuries is critical to minimizing morbidity and mortality.