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.

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.

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).

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.

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.

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.

Indications for and Risks Associated With Implant Removal After Pediatric Trauma.

A wide range of implants are used in the treatment of pediatric fractures, including wires, plates, screws, flexible rods, rigid rods, and external fixation devices. Pediatric bones differ from adult bones both mechanically and biologically, including the potential for remodeling. Implants used in pediatric trauma patients present a unique set of circumstances regarding indications, risks, timing of implant removal, weight-bearing restrictions, and long-term sequelae. Indications for implant removal include wire/pin fixation, when substantial growth remains, and infection. When considering implant removal, the risks and benefits must be assessed. The primary risk of implant removal is refracture. The timing of implant removal varies widely from several weeks to a year or more with the option of retention depending on the fracture, type of implant, and skeletal maturity of the patient.

Radial Width of the Lateral Meniscus at the Popliteal Hiatus: Relevance to Saucerization of Discoid Lateral Menisci.

BACKGROUND: A discoid lateral meniscus (DLM) is a congenital anomaly of the knee in which the lateral meniscus has an "O" shape and contains irregular, abnormal collagenous tissue. A DLM can cause mechanical symptoms and pain. Treatment of a symptomatic DLM is arthroscopic saucerization to reshape the meniscus to a more normal contour. Enough tissue must be removed to eliminate mechanical symptoms but not too much to create instability. The residual width of the meniscus is crucial at the popliteus hiatus because here the peripheral rim is unattached at the capsule. Reports in the literature recommend a residual width of 6 to 8 mm. PURPOSE/HYPOTHESIS: The purpose of this research was to determine the width of the lateral meniscus at the popliteal hiatus in normal specimens. Our null hypothesis was that a residual width of 6 to 8 mm will be sufficient to approximate normal anatomy. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: We made direct measurements of the radial width of the lateral meniscus from the outer rim at the popliteal hiatus to the inner edge in 19 specimens (age, 2-120 months.) We measured one 4-year-old specimen with a bilateral complete DLM. We also measured 39 digital images of specimens (age, 1-132 months) using ImageJ. Finally, we made direct arthroscopic measurements of 8 skeletally mature specimens. RESULTS: The average width of specimens <3 years old was 5.5 mm. The average width of the 10-year-old specimens was 12 mm. The average width of the skeletally mature specimens was 16 mm. A 4-year-old DLM specimen measured 19 mm. CONCLUSION: We rejected our null hypothesis. Direct measurements suggest that a residual width of 6 to 8 mm is insufficient for children ≥8 years old. A width of at least a full centimeter approximates the normal for 8-year-olds and at least 15 mm for adolescents.

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.

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.

Bilateral Medial Patella Sleeve Fractures in a Child: A Case Report.

CASE: An 8-year-old girl presented with a displaced right medial patella sleeve fracture. She underwent open reduction and suture fixation. Three years later, she presented with a left medial patella sleeve fracture that was less displaced than on the right. This was treated with immobilization and structured rehabilitation. She was able to return to full activity with normal radiographs at the final follow-up. CONCLUSION: Patella sleeve fractures are rare. We report a unique case of bilateral medial patella sleeve fractures in an otherwise healthy child in which one side was treated operatively and the other was treated nonoperatively.

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.

Late Stabilization of Developmental Dysplasia of the Hip Without Treatment: A Case Report.

CASE: Approximately three-quarters of neonates with unstable hips will spontaneously stabilize without treatment in the first few weeks of life. This report presents the long-term follow-up of an infant with developmental dysplasia of the hips that stabilized at an older age and without any orthopaedic treatment. CONCLUSIONS: Factors contributing to the spontaneous stabilization in this case included the patient's self-selected lower extremity position of comfort with hips flexed, abducted, and externally rotated; her delayed walking; and her light body weight.

Fracture of the Supracondylar Process in a Child: A Case Report and Review of the Literature.

CASE: A 5-year-9-month-old boy sustained a fracture of the supracondylar process of the distal humerus. The fracture healed with cast immobilization and with no neurovascular complications. Magnetic resonance imaging showed the medial nerve and the brachial artery to be located under the ligament of Struthers that extended from the supracondylar process to the medial epicondyle. CONCLUSIONS: Fracture of the supracondylar process of the humerus in children is rare and easy to misdiagnose, but once discovered, the fracture can be treated successfully with cast immobilization and without compromise to the neurovascular structures passing under the ligament of Struthers.

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.

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.

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.

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.