The effect of sodium-glucose cotransporter-2 inhibitors on inflammatory biomarkers: A meta-analysis of randomized controlled trials.

AIMS: To conduct a meta-analysis of randomized controlled trials (RCTs) to assess the effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors on inflammatory biomarkers. METHODS: Medline, Embase and the Cochrane Library were searched for RCTs investigating the effect of SGLT2 inhibitors on inflammatory biomarkers, adipokine profiles and insulin sensitivity. RESULTS: Thirty-eight RCTs were included (14 967 participants, 63.3% male, mean age 62 ± 8.6 years) with a median (interquartile range) follow-up of 16 (12-24) weeks. Meta-analysis showed that SGLT2 inhibitors significantly improved adiponectin, interleukin-6, tumour necrosis factor receptor-1 (vs. placebo alone: standardized mean difference [SMD] 0.34 [95% confidence interval {CI} 0.23, 0.45], mean difference [MD] -0.85 pg/mL [95% CI -1.32, -0.38], SMD -0.13 [95% CI -0.20, -0.06], respectively), leptin and homeostatic model assessment of insulin resistance index (vs. CONTROL: SMD -0.20 [95% CI -0.33, -0.07], MD -0.83 [95% CI -1.32, -0.33], respectively). There were no significant changes in C-reactive protein (CRP), tumour necrosis factor-α, plasminogen activator inhibitor-1, fibroblast growth factor-21 or monocyte chemoattractant protein-1. CONCLUSIONS: Our analysis shows that SGLT2 inhibitors likely improve adipokine biomarkers and insulin sensitivity, but there is little evidence that SGLT2 inhibitors improve other inflammatory biomarkers including CRP.

An active fixation quadripolar left ventricular lead for cardiac resynchronization therapy with reduced postoperative complication rates.

BACKGROUND: The rate of left ventricular (LV) lead displacement after cardiac resynchronization therapy (CRT) remains high despite improvements in lead technology. In 2017, a novel quadripolar lead with active fixation technology became available in the UK. METHODS: This was a retrospective, observational study analyzing device complications in 476 consecutive patients undergoing successful first-time implantation of a CRT device at a tertiary center from 2017 to 2020. RESULTS: Both active (n = 135) and passive fixation (n = 341) quadripolar leads had similar success rates for implantation (99.3% vs. 98.8%, p = 1.00), although the pacing threshold (0.89 [0.60-1.25] vs. 1.00 [0.70-1.60] V, p = .01) and lead impedance (632 [552-794] vs. 730 [636-862] Ohms, p < .0001) were significantly lower for the active fixation lead. Patients receiving an active fixation lead had a reduced incidence of lead displacement at 6 months (0.74% vs. 4.69%, p = .036). There was no significant difference in the rate of right atrial (RA) and right ventricular (RV) lead displacement between the two groups (RA: 1.48% vs. 1.17%, p = .68; RV: 2.22% vs. 1.76%, p = .72). Reprogramming the LV lead after displacement was unsuccessful in most cases (successful reprogramming: Active fix = 0/1, Passive fix = 1/16) therefore nearly all patients required a repeat procedure. As a result, the rate of intervention within 6 months for lead displacement was significantly lower when patients were implanted with the active fixation lead (0.74% vs. 4.40%, p = .049). CONCLUSION: The novel active fixation lead in our study has a lower incidence of lead displacement and re-intervention compared to conventional quadripolar leads for CRT.

Type VII All-epiphyseal Fractures of the Lateral Malleolus and the Origin of Subfibular Ossicles.

BACKGROUND: A subfibular ossicle (SO), also known as an os subfibulare, is present in ∼1% of the general population. Two theories have been proposed to explain the origin of SOs: (1) as a failure of fusion of a secondary center of ossification; (2) as a posttraumatic sequela. This report offers prospective, longitudinal radiographic evidence for the formation of SOs as a posttraumatic sequela of type VII transepiphyseal fractures of the lateral malleolus in children. METHODS: This Institutional Review Board-approved study was performed at a tertiary care pediatric hospital from March 2012 to April 2019. The study group included 37 children with a type VII fracture of the lateral malleolus and a minimum follow-up of 6 months. RESULTS: Twenty-one children (57%) healed their fracture. Sixteen children (43%) went on to form SOs. The most common location for the fractures was the distal third of the epiphysis, and the most common fracture type forming SOs was a sleeve avulsion fracture. Four of the children forming SOs have had surgery to address pain and recurrent sprains. CONCLUSIONS: Overall, 43% of children who sustained a type VII fracture of the lateral malleolus went on to form SOs, giving support to the posttraumatic theory of origin. Sleeve avulsion fractures have the greatest chance of forming SOs. So far, 4 of the 16 children forming SOs have undergone surgery for ankle pain and recurrent sprains. LEVEL OF EVIDENCE: Level II.

Remodeling of Sagittal Plane Malunion After Pediatric Supracondylar Humerus Fractures.

BACKGROUND: Pediatric supracondylar humeral fractures (SCHFs) can heal in hyperextension malunion after casting or surgical treatment. Here the authors present quantitative evidence concerning the ability of children to remodel sagittal plane malunion. Their null hypothesis was that like varus and valgus malunion, children have little capacity to remodel sagittal plane malunion after SCHFs. METHODS: The authors performed a prospective longitudinal radiographic study of 41 children, aged 22 to 126 months, who were registered during the study interval. They calculated the percent displacement of the center of the capitellum behind the anterior humeral line (AHL) as the distance of the midpoint of the capitellum from the AHL, divided by the diameter of the capitellum, multiplied by 100. Longitudinal measurements were made using the embedded software on our institution's digital radiographic system. The primary outcome focus was the percent displacement of the center of the capitellum relative to AHL on the initial and on the latest radiograph. RESULTS: The average initial displacement (hyperextension) of the capitellum behind the AHL for all patients was 61% (range, 23% to 134%). At an average follow-up of 21 months, 24 children (60%) had remodeled 100% the sagittal plane malunion, 12 children (30%) had remodeled such that the AHL passed through the central third of the capitellum, and 5 children (10%) had minimal or no remodeling. CONCLUSIONS: The authors rejected their null hypothesis. Children do have the capacity to remodel radiographically measurable sagittal plane malunion of SCHFs. Children younger than 5 years of age can remodel 100% displacement of the center of the capitellum, whereas those over 8 years of age have minimal remodeling capacity.

Trans-Metaphyseal Screws Placed in Children: An Argument for Monitoring and Potentially Removing the Implants.

BACKGROUND: Surgeons frequently use trans-metaphyseal screws in children to achieve osteosynthesis after fractures or stability after reconstructive osteotomies. Screws that were initially inserted below the cortex of bone can become prominent and symptomatic due to the process of funnelization that narrows the wide metaphysis to the diameter of the thinner diaphysis. METHODS: Case series presentation of 11 children who presented with screw prominence after the cutback process range in age from 19 to 169 months. We used the screws as radiographic markers to quantitate the amount of bone "cutback" or lost during the process of funnelization. RESULTS: The average length of screw protrusion beyond the edge of the bone when symptomatic was 8.7 mm (range, 3.3 to 14.3 mm). Time from implantation to the last radiograph averaged 40 months (range, 19 to 84 mo). The average loss of bone width at the time of presentation was 21% (range, 7% to 36%). CONCLUSIONS: These cases suggest that orthopaedic surgeons should consider monitoring children after implantation of trans-metaphyseal screws and informing parents and patients about the possibility of screw prominence necessitating removal due to the process of metaphyseal funnelization. LEVEL OF EVIDENCE: Level IV.

Endocardial left ventricular pacing for cardiac resynchronization: systematic review and meta-analysis.

Aims: Endocardial left ventricular (LV) pacing for Cardiac Resynchronization Therapy has been proposed as an alternative to conventional LV lead placement via the coronary sinus. In order to assess the relative benefits and risks of this technique, we have performed a meta-analysis of published reports. Methods and results: A systemic search was performed using online databases to identify studies of lead-based endocardial pacing. A random-effects meta-analysis was performed, to assess the rate of complications and clinical response (defined as ≥1 decrease in NYHA class). We selected 23 studies, including 384 patients. The trans-atrial septal technique was used in 20 studies, 1 used the trans-ventricular apical technique, and 2 used the trans-ventricular septal technique. Mean age was 66 years, male 66%, EF 26%, NYHA class 3.0. Procedural success rates were over 95% in all studies. Clinical response was reported by 16 studies for 262 patients, giving a response estimate of 82% (95% CI 71-89%). There was significant heterogeneity, and response in the only large study was 59%. Thromboembolic (TE) complications were reported by all studies, over 22 ±32 months follow up. The rate of stroke was 2.5 events per 100 patient years (95% CI 1.5-4.3), and TIA 2.6 (1.1-6.1). The mortality rate was 4.5 (1.5-13.6) per 100 patient years. Conclusion: LV endocardial pacing appears to be a viable technique when conventional lead placement is not possible. Response rates were heterogeneous but comparable with conventional CRT. There is likely to be a small increase over expected rates of stroke, although included patients were high risk.

Electrical latency predicts the optimal left ventricular endocardial pacing site: results from a multicentre international registry.

Aims: The optimal site for biventricular endocardial (BIVENDO) pacing remains undefined. Acute haemodynamic response (AHR) is reproducible marker of left ventricular (LV) contractility, best expressed as the change in the maximum rate of LV pressure (LV-dp/dtmax), from a baseline state. We examined the relationship between factors known to impact LV contractility, whilst delivering BIVENDO pacing at a variety of LV endocardial (LVENDO) locations. Methods and results: We compiled a registry of acute LVENDO pacing studies from five international centres: Johns Hopkins-USA, Bordeaux-France, Eindhoven-The Netherlands, Oxford-United Kingdom, and Guys and St Thomas' NHS Foundation Trust, London-UK. In all, 104 patients incorporating 687 endocardial and 93 epicardial pacing locations were studied. Mean age was 66 ± 11 years, mean left ventricular ejection fraction 24.6 ± 7.7% and mean QRS duration of 163 ± 30 ms. In all, 50% were ischaemic [ischaemic cardiomyopathy (ICM)]. Scarred segments were associated with worse haemodynamics (dp/dtmax; 890 mmHg/s vs. 982 mmHg/s, P < 0.01). Delivering BiVENDO pacing in areas of electrical latency was associated with greater improvements in AHR (P < 0.01). Stimulating late activating tissue (LVLED >50%) achieved greater increases in AHR than non-late activating tissue (LVLED < 50%) (8.6 ± 9.6% vs. 16.1 ± 16.2%, P = 0.002). However, the LVENDO pacing location with the latest Q-LV, was associated with the optimal AHR in just 62% of cases. Conclusions: Identifying viable LVENDO tissue which displays late electrical activation is crucial to identifying the optimal BiVENDO pacing site. Stimulating late activating tissue (LVLED >50%) yields greater improvements in AHR however, the optimal location is frequently not the site of latest activation.

Thrombo-embolic events in left ventricular endocardial pacing: long-term outcomes from a multicentre UK registry.

Aims: Endocardial left ventricular (LV) pacing is a viable alternative in patients with failed coronary sinus (CS) lead implantation. However, long-term thrombo-embolic risk remains unknown. Much of the data have come from a small number of centres. We examined the safety and efficacy of endocardial LV pacing to determine the long-term thrombo-embolic risk. Methods and results: Registries from four UK centres were combined to include 68 patients with endocardial leads with a mean follow-up of 20 months. These were compared to a matched 1:2 control group with conventional CS leads. Medical records were reviewed, and patients contacted for follow-up. Ischaemic stroke occurred in four patients (6%) in the endocardial arm providing an annual event rate (AER) of 3.6% over a 20 month follow-up; compared to 9 patients (6.6%) amongst controls with an AER of 3.4% over a 23-month follow-up. Regression analyses showed a significant association between sub-therapeutic international normalized ratio and stroke (P = 0.0001) in the endocardial arm. There was no association between lead material and mode of delivery (transatrial/transventricular) and stroke. Mortality rate was 12 and 15 per 100 patient years in the endocardial and control arm respectively with end-stage heart failure being the commonest cause. Conclusion: Endocardial LV lead in heart failure patients has a good success rate at 1.6 year follow-up. However, it is associated with a thrombo-embolic risk (which is not different from conventional CS leads) attributable to sub-therapeutic anticoagulation. Randomized control trials and studies on non-vitamin K antagonist oral anticoagulants are required to ascertain the potential of widespread clinical application of this therapeutic modality.

Transepiphyseal (Type VII) Ankle Fracture Versus Os Subfibulare in Pediatric Ankle Injuries.

BACKGROUND: Pediatric ankle injuries are common, giving rise to ∼17% of all physeal injuries. An os subfibulare in a child with an ankle sprain may be confused with a type VII transepiphyseal fracture. Here, we evaluate the clinical and radiographic features of type VII transepiphyseal fractures to those of os subfibulare presenting with acute ankle trauma with the hypothesis that radiographs are necessary for final diagnosis and neither clinical history nor examination would be diagnostic. METHODS: We performed an internal review board-approved, retrospective chart review of patients identified with a traumatic os subfibulare or type VII ankle fracture over an 18-month period. Charts were reviewed for demographics, mechanism, and clinical findings on initial presentation. Radiographic measurements of the distal fibular fragment as well as epiphysis were made on presenting ankle series radiographs. RESULTS: A total of 23 patients were identified. Eleven patients had a traumatic type VII ankle fracture and 12 had trauma associated with an os subfibulare on initial radiographs. The history and clinical presentations were similar and were nondiagnostic. The ratio of the width of the fibula at its largest point on the anterior posterior view to the width of the fibular fragment was significantly larger in the type VII ankle fractures (P=0.05). All os subfibulare were located within the inferior third of the epiphysis, whereas all type VII fractures were either at the equator or within the middle third of the fibular epiphysis. CONCLUSIONS: Radiographs, not clinical presentation, can differentiate an os subfibulare from a type VII transepiphyseal fracture. Children with type VII fractures have a long, irregular fracture line within the middle third of the distal fibular epiphysis. Those with an ankle sprain and os subfibulare have a smooth-edged ossicle of relatively short length located within the inferior pole of the epiphysis. Furthermore, the radiographic width of the fragment in the type VII fractures is significantly larger in width than the os subfibulare. LEVEL OF EVIDENCE: Level II.

AN OVERVIEW OF THE EFFICACY OF THE 12-STEP GROUP THERAPY FOR SUBSTANCE ABUSE TREATMENT.

This study was designed to determine if 12-Steps groups efficacy for substance abuse treatment significantly improve abstinence rates of heroin addicts in the short run and long run (1-year and 5-year period); and if abstinence rates are found to be lower for heroin addicts that have attended 12-Step groups at the 1-year mark, and if similar results would be expected at the 5-year mark. Secondary data from the Inter-University Consortium of Political and Social Research (ICPSR) was extracted and analyzed for the aforementioned hypothesis. Using SSPS to test the research hypothesis for the 1-Year Follow Up, the chi-square test shows a p-value below of .10, and the analysis determined that there was significant evidence to support the hypothesis that cases in a 12-Steps or self-help program have a higher success than cases not in a program for the 1-year follow up. For 5-Year Follow Up, the cases that attended a 12-Step program or a self-help program and about 27% went on to use heroin during the last 12 months compared to 34% cases that did not go to a program.

Cardiac Resynchronization Therapy Delivered Via a Multipolar Left Ventricular Lead is Associated with Reduced Mortality and Elimination of Phrenic Nerve Stimulation: Long-Term Follow-Up from a Multicenter Registry.

INTRODUCTION: Cardiac resynchronization therapy (CRT) using quadripolar left ventricular (LV) leads provides more pacing vectors compared to bipolar leads. This may avoid phrenic nerve stimulation (PNS) and allow optimal lead placement to maximize biventricular pacing. However, a long-term improvement in patient outcome has yet to be demonstrated. METHODS: A total of 721 consecutive patients with conventional CRTD criteria implanted with quadripolar (n = 357) or bipolar (n = 364) LV leads were enrolled into a registry at 3 UK centers. Lead performance and mortality was analyzed over a 5-year period. RESULTS: Patients receiving a quadripolar lead were of similar age and sex to those receiving a bipolar lead, although a lower proportion had ischemic heart disease (62.6% vs. 54.1%, P = 0.02). Both groups had similar rates of procedural success, although lead threshold, impedance, and procedural radiation dose were significantly lower in those receiving a quadripolar lead. PNS was more common in those with quadripolar leads (16.0% vs. 11.6%, P = 0.08), but was eliminated by switching pacing vector in all cases compared with 60% in the bipolar group (P < 0.001). Furthermore, LV lead displacement (1.7% vs. 4.6%, P = 0.03) and repositioning (2.0% vs. 5.2%, P = 0.03) occurred significantly less often in those with a quadripolar lead. All-cause mortality was also significantly lower in the quadripolar compared to bipolar lead group in univariate and multivariate analysis (13.2% vs. 22.5%, P < 0.001). CONCLUSIONS: In a large, multicenter experience, the use of quadripolar LV leads for CRT was associated with elimination of PNS and lower overall mortality. This has important implications for LV pacing lead choice.

Learning leadership skills in practice through quality improvement.

The development of leadership skills in doctors in training is essential to support both their professional development and the future supply of clinical leaders the NHS so desperately needs. There is, however, limited opportunity in current training programmes for trainees to learn and develop these skills, and what opportunity there is has often focused on management rather than leadership skills. Involvement in trainee-led supported quality improvement projects can teach these skills. We summarise the current limitations in leadership training and discuss how the College's 'Learning To Make a Difference' programme, and others like it, are helping to teach leadership.

The effect of sodium-glucose co-transporter 2 inhibitors on outcomes after cardiac resynchronization therapy.

AIMS: The trials upon which recommendations for the use of cardiac resynchronization therapy (CRT) in heart failure used optimal medical therapy (OMT) before sodium-glucose co-transporter 2 inhibitors (SGLT2i). Moreover, the SGLT2i heart failure trials included only a small proportion of participants with CRT, and therefore, it remains uncertain whether SGLT2i should be considered part of OMT prior to CRT. METHODS AND RESULTS: We compared electrocardiogram (ECG) and echocardiographic responses to CRT as well as hospitalization and mortality rates in consecutive patients undergoing implantation at a large tertiary centre between January 2019 to June 2022 with and without SGLT2i treatment. Three hundred seventy-four participants were included aged 74.0 ± 11.5 years (mean ± standard deviation), with a left ventricular ejection fraction (LVEF) of 31.8 ± 9.9% and QRS duration of 161 ± 29 ms. The majority had non-ischaemic cardiomyopathy (58%) and were in NYHA Class II/III (83.6%). These characteristics were similar between patients with (n = 66) and without (n = 308) prior SGLT2i treatment. Both groups demonstrated similar evidence of response to CRT in terms of QRS duration shortening, and improvements in LVEF, left ventricular end-diastolic inner-dimension (LVIDd) and diastolic function (E/A and e/e'). While there was no difference in rates of hospitalization (for heart failure or overall), mortality was significantly lower in patients treated with SGLT2i compared with those who were not (6.5 vs. 16.6%, P = 0.049). CONCLUSIONS: We observed an improvement in mortality in patients undergoing CRT prescribed SGLT2i compared with those not prescribed SGLT2i, despite similar degrees of reverse remodelling. The authors recommend starting SGLT2i prior to CRT implantation, where it does not delay implantation.

Outpatient treatment of decompensated heart failure: A systematic review and study level meta-analysis.

Patients with acutely decompensated heart failure (ADHF) are usually admitted to hospital for management. There is growing interest in delivering intravenous (IV) diuretic therapy at home, in the community or at hospital day-care units; the safety and effectiveness of outpatient-based management (OPM) for ADHF has not been established. We conducted a systematic literature review and meta-analysis to investigate the short-term safety and effectiveness of OPM compared with inpatient management (IPM) of ADHF. Pre-specified endpoints were 30 day mortality and 30 day hospitalization. The meta-analysis was conducted using RevMan 5.4 software. Twenty-nine studies of OPM were identified, including 7683 patients. Only five studies directly compared OPM (n = 1303) with IPM (n = 2047), including three observational studies, and two randomized controlled trials (RCTs). The other 24 studies only stated OPM outcomes. For the five studies comparing IPM versus OPM, patients were generally aged >75 years and of similar age for each strategy, with a similar proportion of men (56%). In a study-level, aggregate analysis, 30 day all-cause mortality was 9.3% (121/1303) for OPM, compared with 15.6% (320/2047) for IPM [OR 0.29 (95% CI 0.09, 0.93) P = 0.04]. Four studies reported 30 day all-cause hospitalization; 22.0% for IPM versus 16.8% for OPM [OR 0.73 (95% CI 0.61, 0.89), P = 0.001]. In the two RCTs, we found no difference in 30 day mortality or hospitalization. In observational studies, OPM of ADHF is associated with lower 30 day hospitalization and lower 30 day mortality; such differences were not observed in two small, single-centre RCTs. A substantial, multicentre RCT is required to confirm the safety and effectiveness of OPM for ADHF.

Dostoevsky, The Brothers Karamazov, and Epilepsy.

Fyodor Mikhailovich Dostoevsky was a brilliant nineteenth-century Russian novelist who had a seizure disorder that influenced his life and his creativity. His novels explore issues of love, faith, doubt, morality and reflect his personal experience with epilepsy. He was a keen observer of familial psychodynamics. The Brothers Karamazov (1880)was Dostoyevsky's longest and last novel, completed just a few months before his death from a pulmonary hemorrhage, most likely related to his life-long habit of cigarette smoking. In this novel, he explores the subtility of interpersonal relationships and the psychopathology within the Karamazov family and how one of the three brothers, Smerdyakov, uses psychogenic non-epileptic seizures as an alibi to get away with the perfect crime of patricide.

Late Presentation of a Retained Wood Foreign Body as an Expanding Soft-Tissue Mass in an Adolescent's Foot: A Case Report.

CASE: A 12-year-5-month-old boy presented with a 3-month history of a 2 × 3-cm enlarging painful mass on the medial plantar aspect of his left foot. The radiograph was normal, but the magnetic resonance (MR) images clearly disclosed a foreign body in the shape of a toothpick that had been quiescent for 31 months. Thirty-three months after surgical removal, the patient was asymptomatic and had returned to full activity. CONCLUSION: A retained wood foreign body can present as an expanding mass, and MR is the modality of choice to image wood foreign bodies.

Management of secondary mitral regurgitation: from drugs to devices.

Severe secondary mitral regurgitation carries a poor prognosis with one in five patients dying within 12 months of diagnosis. Fortunately, there are now a number of safe and effective therapies available to improve outcomes. Here, we summarise the most up-to-date treatments. Optimal guideline-directed medical therapy is the mainstay therapy and has been shown to reduce the severity of mitral regurgitation in 40-45% of patients. Rapid medication titration protocols reduce heart failure hospitalisation and facilitate earlier referral for device therapy. The pursuit of sinus rhythm in patients with atrial fibrillation has been shown to significantly reduce mitral regurgitation severity, as has the use of cardiac resynchronisation devices in patients who meet guideline-directed criteria. Finally, we highlight the key role of mitral valve intervention, particularly transcatheter edge-to-edge repair (TEER) for management of moderate-severe mitral regurgitation in carefully selected patients with poor left ventricular systolic function, with a number needed to treat of 3.1 to reduce heart failure hospitalisation and 5.9 to reduce all-cause death. To slow the rapid accumulation of morbidity and mortality, we advocate a proactive approach with accelerated medical optimisation, followed by management of atrial fibrillation and cardiac resynchronisation therapy if indicated, then, rapid referral to the Heart Team for consideration of mitral valve intervention in patients with ongoing symptoms and at least moderate-severe mitral regurgitation. Mitral TEER has been shown to be 'reasonably cost-effective' (but not cost-saving) in the UK in selected patients, although TEER remains underused with only 6.5 procedures per million population (pmp) compared with Germany (77 pmp), Switzerland (44 pmp) and the USA (32 pmp).

Knee valgus and patellofemoral instability after pediatric anterior cruciate ligament reconstruction: a case report and review of the literature.

BACKGROUND: Pediatric athletes who undergo anterior cruciate ligament reconstruction are at risk for a growth deformity if the surgery violates the physes. CASE: A 12-year-old African American boy underwent anterior cruciate ligament reconstruction using a hamstring autograft. The procedure violated the distal femoral growth plate and the perichondrial ring of LaCroix, resulting in a distal femoral lateral physeal growth arrest. Three years later, he had developed a 15° valgus deformity, an increased quadriceps angle and patellofemoral instability. He was able to return to sports after undergoing a distal femoral osteotomy to correct the valgus and medial patellofemoral ligament reconstruction to stabilize the patella. CONCLUSION: Anterior cruciate ligament reconstruction in athletes with open physes has the potential to cause distal femoral valgus deformity, an increased quadriceps angle, and subsequent patellofemoral instability.