Follow-up of women with cervical adenocarcinoma in situ treated by conization: A single centre clinical experience.

OBJECTIVE: Hysterectomy has been the historical gold standard final step in the treatment algorithm of adenocarcinoma in situ (AIS) recommended by most North American colposcopy guidelines. AIS disproportionately affects young childbearing age women, therefore a fertility sparing treatment option is desirable. Our study examines the impact of conservative treatment of AIS with conization followed by serial surveillance. METHODS: A retrospective chart review was completed of patients treated for AIS from 2006 to 2020. Charts were identified by pathologic diagnosis of AIS on cervical and uterine specimens. Charts were excluded if AIS was not treated with conization, if AIS was not confirmed on initial conization specimen, or if invasive disease was found at initial conization. RESULTS: 121 patient charts were analyzed. Median age of patients at first conization and hysterectomy was 34.8 and 40.9, respectively. First conization was by Cold Knife Cone in 58% of patients, and by Loop Electrosurgical Excisional Procedure in 42% of patients. Median follow-up period in our study was 609 days. 5% of patients had recurrence, with only one patient who recurred as cancer. One case of recurrence had a positive initial conization margin. Median time to recurrence was 700 days. 47% of patients underwent eventual hysterectomy. Residual AIS was found in 23% of hysterectomy specimens. Adenocarcinoma was diagnosed on hysterectomy specimen in four patients. CONCLUSION: Our study demonstrates the oncologic safety of treating AIS with conization and serial surveillance. Routine hysterectomy completed as a part of the AIS treatment algorithm, as in current clinical guidelines, is unnecessary.

Efficient management of new patient referrals to a breast service: the safe introduction of an advanced nurse practitioner-led telephone breast pain service.

INTRODUCTION: There has been an almost 100% increase in referrals to breast cancer diagnostic clinics in the past decade. Breaching of the two-week cancer referral target is now commonplace, potentially delaying diagnoses of breast malignancy in many women. Almost one in five of these referrals are women with mastalgia, not a symptom linked to breast cancer. The objective of the study was the safe introduction of an advanced nurse practitioner-led telephone service for women with mastalgia to improve the service for women and create capacity for those with "red flag" breast symptoms. METHODS: Referrals to clinic were triaged, women with mastalgia only were directed to a telephone-based assessment clinic and symptoms evaluated using a multidisciplinary created proforma. RESULTS: Within 23 months, 1,427 women were assessed in the breast pain telephone assessment clinic: 863 (61%) were aged over 40 and 564 (39%) aged under 40. A total of 1,238 underwent telephone assessment. Reassurance and discharge only was needed for 365 (26%). The aetiology of pain was identified as musculoskeletal in 1,104/1,238 (89%) of patients, with only 39/1,238 (3.2%) identified as having true breast pain. Additional symptoms were mentioned by 264 women (18%) during the consultation; all immediately redirected back to a diagnostic clinic. Mammography was undertaken in 609 women (43%). Seven women (0.6%) were diagnosed with a breast malignancy. Patient survey indicated that 93% of patients were satisfied with the care received and 97% said they would recommend the service to a family member or friend. CONCLUSIONS: Although face-to-face assessments for breast pain remain the standard practice in many breast units, data indicating the safety of a telephone assessment clinic, along with high levels of patient satisfaction, question whether services can be delivered differently.

A new clinical sign to detect radiologically occult greater tuberosity fractures.

INTRODUCTION: Up to 59% of undisplaced greater tuberosity (GT) fractures are missed on initial evaluation. Timely diagnosis of these injuries can avoid undue morbidity, but a clinical sign to accurately identify them has not previously been described. Magnetic resonance imaging (MRI) remains the gold standard for their assessment but may not be routinely available, or difficult to organize urgently. We aimed to evaluate the diagnostic efficacy of a new clinical sign (the anterior bruise sign [ABS]), in diagnosing radiologically occult GT fractures. METHODS: Over a 4-year period, 59 patients who sustained a traumatic shoulder injury with no fracture on initial radiographs were referred to a specialist shoulder clinic within a week of their injury and enrolled in a prospective observational cohort study. At initial presentation, the presence of anterior arm bruising extending to the mid-diaphysis was recorded as a positive ABS. MRI assessment of the injured shoulder was performed in all patients at first follow-up. Presenting radiographs, 2-week radiographs, and MRI scans were reviewed by a musculoskeletal radiologist. The diagnostic value of a positive ABS was compared with 2-week radiographs, and other clinical tests. RESULTS: The mean age of the cohort was 58.5 (range 30-79) years, and 27 (45.8%) were female. The mean time from injury to first follow-up was 6.9 (standard deviation 2.4) days. MRI revealed that 25 of 59 patients (42.4%) had an undisplaced GT fracture. The overall accuracy of the ABS in identifying occult GT fractures was 98% (sensitivity = 100%, specificity = 97%, positive predictive value = 96%, negative predictive value = 100%, P < .001). In contrast, radiographs taken at 2 weeks postinjury were less accurate (71.2%) (P < .001), and other clinical assessments of cuff function had much lower accuracy. CONCLUSION: In patients presenting with a traumatic shoulder injury with normal radiographs, the ABS is a highly sensitive and specific clinical aid to identify patients with an occult GT fracture.

Grain Characteristics, Moisture, and Specific Peptides Produced by Ustilaginoidea virens Contribute to False Smut Disease in Rice (Oryza sativa L.).

The fungus Ustilaginoidea virens, the causative agent of false smut in rice (Oryza sativa L.), is responsible for one of the severe grain diseases that lead to significant losses worldwide. In this research, microscopic and proteomic analyses were performed by comparing U. virens infected and non-infected grains of the susceptible and resistant rice varieties to provide insights into the molecular and ultrastructural factors involved in false smut formation. Prominent differentially expressed peptide bands and spots were detected due to false smut formation as revealed by sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and two-dimensional gel electrophoresis (2-DE) SDS-PAGE profiles and were identified using liquid chromatography-mass spectrometry (LC-MS/MS). The proteins identified from the resistant grains were involved in diverse biological processes such as cell redox homeostasis, energy, stress tolerance, enzymatic activities, and metabolic pathways. It was found that U. virens produces diverse degrading enzymes such as ß-1, 3-endoglucanase, subtilisin-like protease, putative nuclease S1, transaldolase, putative palmitoyl-protein thioesterase, adenosine kinase, and DNase 1 that could discretely alter the host morphophysiology resulting in false smut. The fungus also produced superoxide dismutase, small secreted proteins, and peroxidases during the smut formation. This study revealed that the dimension of rice grain spikes, their elemental composition, moisture content, and the specific peptides produced by the grains and the fungi U. virens play a vital role in the formation of false smut.

Functional outcome after nonoperative management of minimally displaced greater tuberosity fractures and predictors of poorer patient experience.

The outcomes following nonoperative management of minimally displaced greater tuberosity (GT) fractures, and the factors which influence patient experience, remain poorly defined. We assessed the early patient-derived outcomes following these injuries and examined the effect of a range of demographic- and injury-related variables on these outcomes. In total, 101 patients (53 female, 48 male) with a mean age of 50.9 years (19 to 76) with minimally displaced GT fractures were recruited to a prospective observational cohort study. During the first year after injury, patients underwent experiential assessment using the Disabilities of the Arm, Shoulder and Hand (DASH) score and assessment of associated injuries using MRI performed within two weeks of injury. The primary outcome was the one-year DASH score. Multivariate analysis was used to assess the effect of patient demographic factors, complications, and associated injuries, on outcome. The mean DASH score improved from 42.3 (SD 9.6) at six weeks post-injury, to 19.5 (SD 14.3) at one-year follow-up (p < 0.001), but outcomes were mixed, with 30 patients having a DASH score > 30 at one year. MRI revealed a range of associated injuries, with a full-thickness rotator cuff tear present in 19 patients (19%). Overall, 11 patients (11%) developed complications requiring further operative intervention; 20 patients (21%) developed post-traumatic secondary shoulder stiffness. Multivariate analysis revealed a high-energy mechanism (p = 0.009), tobacco consumption (p = 0.033), use of mobility aids (p = 0.047), a full-thickness rotator cuff tear (p = 0.002), and the development of post-traumatic secondary shoulder stiffness (p = 0.035) were independent predictors of poorer outcome. The results of nonoperative management of minimally displaced GT fractures are heterogeneous. While many patients have satisfactory early outcomes, a substantial subgroup fare much worse. There is a high prevalence of rotator cuff injuries and post-traumatic shoulder stiffness, and their presence is associated with poorer patient experience. Furthermore, patients who have a high-energy injury, smoke, or use walking aids, have worse outcomes.

Factors affecting a patient's experience following the open Latarjet procedure to treat recurrent anterior shoulder instability.

The open Latarjet procedure is a widely used treatment for recurrent anterior instability of the shoulder. Although satisfactory outcomes are reported, factors which influence a patient's experience are poorly quantified. The aim of this study was to evaluate the effect of a range of demographic factors and measures of the severity of instability on patient-reported outcome measures in patients who underwent an open Latarjet procedure at a minimum follow-up of two years. A total of 350 patients with anterior instability of the shoulder who underwent an open Latarjet procedure between 2005 and 2018 were reviewed prospectively, with the collection of demographic and psychosocial data, preoperative CT, and complications during follow-up of two years. The primary outcome measure was the Western Ontario Shoulder Instability Index (WOSI), assessed preoperatively, at two years postoperatively, and at mid-term follow-up at a mean of 50.6 months (SD 24.8) postoperatively. The secondary outcome measure was the abbreviated version of the Disabilities of the Arm, Shoulder and Hand (QuickDASH) score. The influence of the demographic details of the patients, measurements of the severity of instability, and the complications of surgery were assessed in a multivariate analysis. The mean age of the patients was 25.5 years (22 to 32) and 27 (7.7%) were female. The median time to surgery after injury was 19 months (interquartile range (IQR) 13 to 39). Seven patients developed clinically significant complications requiring further intervention within two years of surgery. The median percentage WOSI deficiency was 8.0% (IQR 4 to 20) and median QuickDASH was 3.0 (IQR 0 to 9) at mid-term assessment. A minority of patients reported a poorer experience, and 22 (6.3%) had a > 50% deficiency in WOSI score. Multivariate analysis revealed that consumption of ≥ 20 units of alcohol/week, a pre-existing affective disorder or epilepsy, medicolegal litigation, increasing time to surgery, and residing in a more socioeconomically deprived area were independently predictive of a poorer WOSI score. Although most patients treated by an open Latarjet procedure have excellent outcomes at mid-term follow-up, a minority have poorer outcomes, which are mainly predictable from pre-existing demographic factors, rather than measures of the severity of instability.

Technical success of endoscopic stenting for malignant gastric outlet obstruction.

BACKGROUND: Palliation of irresectable malignant gastric outlet obstruction (GOO) using self-expanding metal stents (SEMS) is gaining popularity with high technical success rates. The aim of this study was to review and compare GOO stenting for malignancy with other series. METHODS: A retrospective review of all patients undergoing pyloroduodenal stenting for malignant GOO at Groote Schuur Hospital, 1 March 2018-31 August 2021, evaluating demographics, technical success, pathology, and stentrelated complications was done. RESULTS: One hundred and fourteen patients, of which 38.6% were female, were included, with gastric malignancies (74.6%) being the most frequent underlying pathology. Median age was 64 years (IQR 53-70 years), with 48.2% having at least one comorbidity. The majority (96 patients; 85.7%) required only one stent. In total, 132 stent insertion attempts were undertaken. Three technical failures were experienced (one incorrect stent placement and two failed insertions), equating to a 97.4% technical success rate. Four immediate complications occurred (3.1%): two related to sedation, one incorrect stent placement and an oesophagogastric junction perforation with procedural death. Fifteen delayed complications occurred: 13 tumour in-growth blockages, one stent fracture and one case of poor radial stent expansion. Stent blockages occurred at a median of 107 days (IQR 80-275 days). Salvage stenting was 100% successful in 14 cases requiring re-stenting. CONCLUSION: Technical insertion success rates of primary and salvage duodenal stenting for malignant GOO are on par with international high-volume units. The leading pathology locally is gastric adenocarcinoma, with palliative stenting remaining a feasible and accessible option.

Delayed acromioclavicular joint reconstruction using a modern suspensory device does not increase the risk of fixation failure or major complications.

BACKGROUND: Management of displaced acromioclavicular joint (ACJ) injuries remains contentious. It is unclear if delayed vs. acute reconstruction has an increased risk of fixation failure and complications. The primary aim of this study was to compare complications of early vs. delayed reconstruction. The secondary aim was to determine modes of failure of ACJ reconstruction requiring revision surgery. METHODS: A retrospective study was performed on all patients who underwent operative reconstruction of ACJ injuries over a 10-year period (Rockwood III-V) using suspensory devices with or without hamstring allograft. Reconstruction was classed as early (<12 weeks from injury) or delayed (≥12 weeks). Patient demographics, fixation method, and postoperative complications were noted, with 1-year follow-up a minimum requirement for inclusion. Patient-reported outcomes with the Disabilities of the Arm, Shoulder, and Hand score and EuroQol-5 Dimension were undertaken. Fixation failure was defined as loss of reduction requiring revision surgery. RESULTS: A total of 104 patients were analyzed (n = 59 early and n = 45 delayed). The mean age was 42.0 (standard deviation: 11.2; 17-70 years); 84.6% were male and 15.4% were smokers. No difference was observed between fixation failure (P = .39) or deep infection (P = .13) with regard to acute vs. delayed reconstruction. No patient demographic or timing of surgery was predictive of fixation failure on regression modeling. Overall, 11 patients underwent revision surgery for loss of reduction and implant failure (n = 5 suture fatigue, n = 2 endobutton escape, n = 2 coracoid stress fracture, and n = 2 deep infection). The EuroQol-5 Dimension (P = .084) and Disabilities of the Arm, Shoulder, and Hand score (P = .062) were comparable for early and delayed groups respectively and below the minimal clinically important difference. CONCLUSION: This study found that delayed surgical management of ACJ injuries using a modern device has comparable functional outcomes and is not associated with a higher incidence of fixation failure or major complications.

Outcomes associated with secondary implant removal and arthrolysis in patients with a painful stiff shoulder after proximal humeral fracture fixation.

AIMS: Open reduction and plate fixation (ORPF) for displaced proximal humerus fractures can achieve reliably good long-term outcomes. However, a minority of patients have persistent pain and stiffness after surgery and may benefit from open arthrolysis, subacromial decompression, and removal of metalwork (ADROM). The long-term results of ADROM remain unknown; we aimed to assess outcomes of patients undergoing this procedure for stiffness following ORPF, and assess predictors of poor outcome. METHODS: Between 1998 and 2018, 424 consecutive patients were treated with primary ORPF for proximal humerus fracture. ADROM was offered to symptomatic patients with a healed fracture at six months postoperatively. Patients were followed up retrospectively with demographic data, fracture characteristics, and complications recorded. Active range of motion (aROM), Oxford Shoulder Score (OSS), and EuroQol five-dimension three-level questionnaire (EQ-5D-3L) were recorded preoperatively and postoperatively. RESULTS: A total of 138 patients underwent ADROM; 111 patients were available for long-term follow-up at a mean of 10.9 years (range 1 to 20). Mean age was 50.8 years (18 to 75);79 (57.2%) were female. Mean time from primary ORPF to ADROM was 11.9 months (6 to 19). Five patients developed superficial wound infection; ten developed symptomatic osteonecrosis/post-traumatic arthrosis (ON/PTA); four underwent revision arthrolysis. Median OSS improved from 17 (interquartile range (IQR) 12.0 to 22.0) preoperatively to 40.0 (IQR 31.5 to 48.0) postoperatively, and 39.0 (IQR 31.5 to 46.5) at long-term follow-up (p < 0.001). Median EQ-5D-3L improved from 0.079 (IQR -0.057 to 0.215) to 0.691 (IQR 0.441 to 0.941) postoperatively, and 0.701 (IQR 0.570 to 0.832) at long-term follow-up (p < 0.001). We found that aROM improved in all planes (p < 0.001). Among the variables assessed on multivariable analysis, a manual occupation, worsening Charlson Comorbidity Index and increasing socioeconomic deprivation were most consistently predictive of worse patient-reported outcome scores. Patients who subsequently developed ON/PTA reported significantly worse one-year and late OSS. CONCLUSION: ADROM in patients with persistent symptomatic stiffness following ORPF can achieve excellent short- and long-term outcomes. More deprived patients, those in a manual occupation, and those with worsening comorbidities have worse outcomes following ADROM. Cite this article: Bone Joint J 2022;104-B(1):157-167.

Functional Outcome After Nonoperative Treatment of a Proximal Humeral Fracture in Adults.

BACKGROUND: The functional outcome following nonoperative treatment of a proximal humeral fracture and the factors that influence it are poorly defined. We aimed to prospectively assess patient-reported outcome measures (PROMs) in a patient cohort at 1 year after the injury. METHODS: In this study, 774 adult patients sustaining a proximal humeral fracture completed PROM assessments, including the Oxford Shoulder Score (OSS), the EuroQol-5 Dimensions-3 Levels (EQ-5D-3L), and visual analog scale (VAS) assessments of pain, health, and overall treatment satisfaction at 1 year. The mean patient age was 65.6 years, and 73.8% of patients were female. The influences of demographic and fracture measurements and complications on the OSS and EQ-5D-3L were assessed. RESULTS: The 1-year mean scores were 33.2 points (95% confidence interval [CI], 32.1 to 34.2 points) for the OSS and 0.58 (95% CI, 0.55 to 0.61) for the EQ-5D-3L. There was considerable heterogeneity in the reported scores, and the 3 demographic variables of higher levels of dependency, higher levels of social deprivation, and a history of affective (mood) disorder were most consistently associated with poorer outcomes, accounting for between 37% and 43% of the score variation. The initial fracture translation potentially leading to nonunion accounted for 9% to 15% of the variation, and a displaced tuberosity fracture was also predictive of 1% to 4% of the outcome variation. There was evidence of a ceiling effect for the OSS, with 238 patients (30.8%) having a score of ≥47 points but a mean outcome satisfaction of only 72.9 points, and this effect was more pronounced in younger, active individuals. At the other end of the spectrum, 239 patients (30.9%) reported an OSS of ≤24 points, and 120 patients (15.5%) had a "worse-than-death" EQ-5D-3L score. CONCLUSIONS: Nonoperative treatment of proximal humeral fractures produces considerable variation in shoulder-specific and general health outcomes at 1 year, and a substantial proportion of patients have poor perceived functional outcomes. The outcome for the majority of less-displaced fractures is mainly influenced by preexisting patient-related psychosocial factors, although the fracture-related factors of displacement, nonunion, and tuberosity displacement account for a small but measurable proportion of the variation and the poorer outcomes in the minority with more severe injuries. LEVEL OF EVIDENCE: Prognostic Level I. See Instructions for Authors for a complete description of levels of evidence.

3D ultrasound reconstruction of sonographic callus : a novel imaging modality for early evaluation of fracture healing.

AIMS: The aim of this study was to establish a reliable method for producing 3D reconstruction of sonographic callus. METHODS: A cohort of ten closed tibial shaft fractures managed with intramedullary nailing underwent ultrasound scanning at two, six, and 12 weeks post-surgery. Ultrasound capture was performed using infrared tracking technology to map each image to a 3D lattice. Using echo intensity, semi-automated mapping was performed to produce an anatomical 3D representation of the fracture site. Two reviewers independently performed 3D reconstructions and kappa coefficient was used to determine agreement. A further validation study was undertaken with ten reviewers to estimate the clinical application of this imaging technique using the intraclass correlation coefficient (ICC). RESULTS: Nine of the ten patients achieved union at six months. At six weeks, seven patients had bridging callus of ≥ one cortex on the 3D reconstruction and when present all achieved union. Compared to six-week radiographs, no bridging callus was present in any patient. Of the three patients lacking sonographic bridging callus, one went onto a nonunion (77.8% sensitive and 100% specific to predict union). At 12 weeks, nine patients had bridging callus at ≥ one cortex on 3D reconstruction (100%-sensitive and 100%-specific to predict union). Presence of sonographic bridging callus on 3D reconstruction demonstrated excellent reviewer agreement on ICC at 0.87 (95% confidence interval 0.74 to 0.96). CONCLUSION: 3D fracture reconstruction can be created using multiple ultrasound images in order to evaluate the presence of bridging callus. This imaging modality has the potential to enhance the usability and accuracy of identification of early fracture healing. Cite this article: Bone Joint Res 2021;10(12):759-766.

Leveraging Radiobiology for Arrhythmia Management: A New Treatment Paradigm?

Radiation therapy is a well-established approach for safely and non-invasively treating solid tumours and benign diseases with high precision and accuracy. Cardiac radiation therapy has recently emerged as a non-invasive treatment option for the management of refractory ventricular tachycardia. Here we summarise existing clinical and preclinical literature surrounding cardiac radiobiology and discuss how these studies may inform basic and translational research, as well as clinical treatment paradigms in the management of arrhythmias.

Adolescent mid-shaft clavicular fracture displacement does not predict nonunion or inferior functional outcome at long-term follow-up.

AIMS: The aim of this study was to define the complications and long-term outcome following adolescent mid-shaft clavicular fracture. METHODS: We retrospectively reviewed a consecutive series of 677 adolescent fractures in 671 patients presenting to our region (age 13 to 17 years) over a ten-year period (2009 to 2019). Long-term patient-reported outcomes (abbreviated version of the Disabilities of the Arm, Shoulder and Hand (QuickDASH) score and EuroQol five-dimension three-level (EQ-5D-3L) quality of life score) were undertaken at a mean of 6.4 years (1.2 to 11.3) following injury in severely displaced mid-shaft fractures (Edinburgh 2B) and angulated mid-shaft fractures (Edinburgh 2A2) at a minimum of one year post-injury. The median patient age was 14.8 years (interquartile range (IQR) 14.0 to 15.7) and 89% were male (n = 594/671). RESULTS: The majority of fractures were mid-shaft (n = 606) with angulation (Edinburgh 2A2, n = 241/606, 39.8%) or displacement (Edinburgh 2B1/2, n = 263/606, 43.4%). Only 7% of the displaced mid-shaft fractures underwent acute fixation (n = 18/263). The incidence of refracture over ten years following nonoperative management of mid-shaft fractures was 3.2% (n = 19/588) and all united without surgery. Fracture type, severity of angulation, or displacement were not associated with refracture. One nonunion occurred following nonoperative management in a displaced mid-shaft fracture (0.4%, n = 1/245). Of the angulated fractures, 61 had angulation > 30°, of which 68.9% (n = 42/61) completed outcome scores with a median QuickDASH of 0.0 (IQR 0.0 to 0.6), EQ-5D-3L 1.0 (1.0 to 1.0), and 98% satisfaction with shoulder function. For the displaced fractures, 127 had displacement beyond one cortical width of bone for which completed outcome scores were provided in 72.4% (n = 92/127). Of these 15 had undergone acute fixation. Following nonoperative treatment, the median QuickDASH was 0.0 (IQR 0.0 to 2.3), EQ-5D-3L 1.0 (1.0 to 1.0), and satisfaction with shoulder function was 95%. There were no significant differences in the patients' demography or functional outcomes between operative and nonoperative treatments. CONCLUSION: Nonoperative management of adolescent mid-shaft clavicle fractures results in excellent functional outcomes at long-term follow-up. Nonunion is exceptionally rare following nonoperative management and the relative indications for surgical intervention in adults do not appear to be applicable to adolescents. Cite this article: Bone Joint J 2021;103-B(5):951-957.

Thermodynamic basis of the α-helix and DNA duplex.

Analysis of calorimetric and crystallographic information shows that the α-helix is maintained not only by the hydrogen bonds between its polar peptide groups, as originally supposed, but also by van der Waals interactions between tightly packed apolar groups in the interior of the helix. These apolar contacts are responsible for about 60% of the forces stabilizing the folded conformation of the α-helix and their exposure to water on unfolding results in the observed heat capacity increment, i.e. the temperature dependence of the melting enthalpy. The folding process is also favoured by an entropy increase resulting from the release of water from the peptide groups. A similar situation holds for the DNA double helix: calorimetry shows that the hydrogen bonding between conjugate base pairs provides a purely entropic contribution of about 40% to the Gibbs energy while the enthalpic van der Waals interactions between the tightly packed apolar parts of the base pairs provide the remaining 60%. Despite very different structures, the thermodynamic basis of α-helix and B-form duplex stability are strikingly similar. The general conclusion follows that the stability of protein folds is primarily dependent on internal atomic close contacts rather than the hydrogen bonds they contain.

Prediction of Nonunion After Nonoperative Treatment of a Proximal Humeral Fracture.

BACKGROUND: The prevalence of nonunion after a proximal humeral fracture (PHF) and the risk factors for its occurrence are poorly defined. We aimed to estimate the rate of nonunion in nonoperatively treated patients and to produce a clinical model for its prediction. METHODS: Two thousand two hundred and thirty adult patients (median age, 72 years [range, 18 to 103 years]; 75.5% were female) with a PHF underwent assessment of fracture union using standard clinical evaluation and conventional radiographs. We assessed the prevalence of nonunion and measured the effect of 19 parameters on healing. Best statistical practices were used to construct a multivariate logistic regression model. The PHF assessment of risk of nonunion model (PHARON) was externally validated in a subsequent prospectively collected population of 735 patients, treated by the same protocol in our institution. RESULTS: Overall, 231 (10.4%) of 2,230 patients developed nonunion. Only 3 (0.8%) of 395 patients with a head-shaft angle (HSA) of >140° developed nonunion; in this cohort, none of the measured candidate variables were independently predictive of nonunion on multivariate logistic regression analysis. In the larger cohort of 1,835 patients with an HSA of ≤140°, 228 (12.4%) developed nonunion. Decreasing HSA, increasing head-shaft translation (HST), and smoking were independently predictive of nonunion on multivariate analysis. The prevalence of nonunion was very low (1%) in the majority with both an HSA of >90° and HST of <50%, whereas the risk was much higher (83.7%) in the 8.3% with an HSA of ≤90° and HST of ≥50%. In both groups, the prevalence of nonunion was much higher in smokers. CONCLUSIONS: The prevalence of nonunion after PHF is higher than previously reported. Most patients have favorable risk-factor estimates and a very low risk of this complication, but a smaller subgroup is at much higher risk. The risk can be accurately estimated with PHARON, using standard clinical assessment tools. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Combined use of two separate but protective vaccine antigens provides protection against Taenia ovis infection in lambs in the presence of protective maternal antibody.

Three recombinant Taenia ovis antigens (To45, To16, To18) each induce protective immunity in lambs or ewes against infection with T. ovis metacestodes. The degree and duration of immunity were assessed in lambs born from vaccinated ewes. Treatment group sizes varied, typically not fewer than 5 animals per group. Ewes were immunised with one T. ovis recombinant protein prior to lambing and the degree and duration of passive immunity in their lambs was assessed by challenge infection up to 18 weeks. Lambs were fully protected up to 6 weeks of age but immunity waned from 6 to 12 weeks and there was no protection when lambs were challenged at 15 weeks. Immunisation of lambs with the homologous recombinant antigen was not effective when vaccinations were given when maternal antibody was high. Lambs were effectively immunised in the presence of passively protective antibody when vaccinated with an antigen that was different to that given to ewes. Vaccination of lambs with a combination of two proteins, To16 and To18, was more effective than giving these single antigens and gave a significant reduction of cyst numbers when lambs were challenged 12 months after immunisation. These results indicate that the use of combinations of T. ovis recombinant antigens could enable complete protection of lambs against infection, if a delivery system becomes available that will maintain antibody at protective levels for 12 months. Alternatively, a third injection given at 6 months may promote the anamnestic response to give long lasting protection.

Sonographic bridging callus at six weeks following displaced midshaft clavicle fracture can accurately predict healing.

AIMS: To evaluate if union of clavicle fractures can be predicted at six weeks post-injury by the presence of bridging callus on ultrasound. METHODS: Adult patients managed nonoperatively with a displaced mid-shaft clavicle were recruited prospectively. Ultrasound evaluation of the fracture was undertaken to determine if sonographic bridging callus was present. Clinical risk factors at six weeks were used to stratify patients at high risk of nonunion with a combination of Quick Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH) ≥ 40, fracture movement on examination, or absence of callus on radiograph. RESULTS: A total of 112 patients completed follow-up at six months with a nonunion incidence of 16.7% (n = 18/112). Sonographic bridging callus was detected in 62.5% (n = 70/112) of the cohort at six weeks post-injury. If present, union occurred in 98.6% of the fractures (n = 69/70). If absent, nonunion developed in 40.5% of cases (n = 17/42). The sensitivity to predict union with sonographic bridging callus at six weeks was 73.4% and the specificity was 94.4%. Regression analysis found that failure to detect sonographic bridging callus at six weeks was associated with older age, female sex, simple fracture pattern, smoking, and greater fracture displacement (Nagelkerke R2 = 0.48). Of the cohort, 30.4% (n = 34/112) had absent sonographic bridging callus in addition to one or more of the clinical risk factors at six weeks that predispose to nonunion. If one was present the nonunion rate was 35%, 60% with two, and 100% when combined with all three. CONCLUSION: Ultrasound combined with clinical risk factors can accurately predict fracture healing at six weeks following a displaced midshaft clavicle fracture. Cite this article: Bone Joint Res 2021;10(2):113-121.

Clinical Characteristics and Outcomes in Patients with COVID-19 and Cancer: a Systematic Review and Meta-analysis.

Much of routine cancer care has been disrupted due to the perceived susceptibility to SARS-CoV-2 infection in cancer patients. Here, we systematically review the current evidence base pertaining to the prevalence, presentation and outcome of COVID-19 in cancer patients, in order to inform policy and practice going forwards. A keyword-structured systematic search was conducted on Pubmed, Cochrane, Embase and MedRxiv databases for studies reporting primary data on COVID-19 in cancer patients. Studies were critically appraised using the NIH National Heart, Lung and Blood Institute's quality assessment tool set. The pooled prevalence of cancer as a co-morbidity in patients with COVID-19 and pooled in-hospital mortality risk of COVID-19 in cancer patients were derived by random-effects meta-analyses. In total, 110 studies from 10 countries were included. The pooled prevalence of cancer as a co-morbidity in hospitalised patients with COVID-19 was 2.6% (95% confidence interval 1.8%, 3.5%, I2: 92.0%). Specifically, 1.7% (95% confidence interval 1.3%, 2.3%, I2: 57.6.%) in China and 5.6% (95% confidence interval 4.5%, 6.7%, I2: 82.3%) in Western countries. Patients most commonly presented with non-specific symptoms of fever, dyspnoea and chest tightness in addition to decreased arterial oxygen saturation, ground glass opacities on computer tomography and non-specific changes in inflammatory markers. The pooled in-hospital mortality risk among patients with COVID-19 and cancer was 14.1% (95% confidence interval 9.1%, 19.8%, I2: 52.3%). We identified impeding questions that need to be answered to provide the foundation for an iterative review of the developing evidence base, and inform policy and practice going forwards. Analyses of the available data corroborate an unfavourable outcome of hospitalised patients with COVID-19 and cancer. Our findings encourage future studies to report detailed social, demographic and clinical characteristics of cancer patients, including performance status, primary cancer type and stage, as well as a history of anti-cancer therapeutic interventions.