The Australian Genomics Mitochondrial Flagship: A National Program Delivering Mitochondrial Diagnoses.

PURPOSE: Families living with mitochondrial diseases (MD) often endure prolonged diagnostic journeys and invasive testing, yet many remain without a molecular diagnosis. The Australian Genomics Mitochondrial flagship, comprising clinicians, diagnostic, and research scientists, conducted a prospective national study to identify the diagnostic utility of singleton genomic sequencing using blood samples. METHODS: 140 children and adults living with suspected MD were recruited using modified Nijmegen criteria (MNC) and randomized to either exome + mtDNA sequencing (ES+mtDNAseq) or genome sequencing (GS). RESULTS: Diagnostic yield was 55% (n=77) with variants in nuclear (n=37) and mtDNA (n=18) MD genes, as well as phenocopy genes (n=22). A nuclear gene etiology was identified in 77% of diagnoses, irrespective of disease onset. Diagnostic rates were higher in pediatric-onset (71%) than adult-onset (31%) cases, and comparable in children with non-European (78%) versus European (67%) ancestry. For children, higher MNC scores correlated with increased diagnostic yield and fewer diagnoses in phenocopy genes. Additionally, three adult patients had a mtDNA deletion discovered in skeletal muscle that was not initially identified in blood. CONCLUSION: Genomic sequencing from blood can simplify the diagnostic pathway for individuals living with suspected MD, especially those with childhood onset diseases and high MNC scores.

Clinical Outcomes of Continuation and Maintenance Electroconvulsive Therapy.

Importance: Large-scale evidence for the efficacy of continuation and maintenance electroconvulsive therapy (c/mECT) is lacking. Objective: To provide an exhaustive and naturalistic insight into the real-world outcomes and the cost-effectiveness of c/mECT in a large dataset. Design, Setting, and Participants: This cohort study included all patients in the Danish National Patient Registry who initiated treatment with ECT from 2003 through 2022. The data were analyzed from October 2023 to February 2024. Exposures: ECT. An algorithm to identify c/mECTs in the dataset was developed: (>3 treatments with ≥7 and <90 days between adjacent treatments, occurring within a time frame of 180 days [cECT] or more [mECT] after an acute [aECT] series). Main Outcomes and Measures: The association of c/mECT with subsequent 6- to 12-month risk of hospitalization or suicidal behavior using Cox proportional hazard regression with multiple adjustments and aECT only as a reference, propensity score matching, and self-controlled case series analysis using a Poisson regression model. A cost-effectiveness analysis based on hospitalization and ECT expenses was made. Results: A total of 19 944 individuals were treated with ECT (12 157 women [61%], 7787 men [39%]; median [IQR] age, 55 [41-70] years). Of these, 1533 individuals (7.7%) received c/mECT at any time point (1017 [5.1%] cECT only and 516 [2.6%] mECT). Compared with patients receiving aECT only, c/mECT patients more frequently experienced schizophrenia (odds ratio [OR], 2.14; 95% CI, 1.86-2.46) and schizoaffective disorder (OR, 2.42; 95% CI, 1.90-3.09) and less frequently unipolar depression (OR, 0.56; 95% CI, 0.51-0.62). In all models, c/mECT was associated with a lower rate of hospitalization after finishing aECT (eg, 6-month adjusted hazard ratio, 0.68; 95% CI, 0.60-0.78 [Cox regression]; 6-month incidence rate ratio, 0.51; 95% CI, 0.41-0.62 [Poisson regression]). There was no significant difference in the risk of suicidal behavior. Compared with the periods before the end of aECT, c/mECT was associated with a substantial reduction in total treatment costs. Conclusions and Relevance: In a nationwide and naturalistic setting, c/mECT after aECT was infrequently used but associated with a lower risk of readmission than aECT alone. The totality of the evidence indicates that c/mECT should be considered more often to prevent relapse after successful aECT in patients whose condition does not respond sufficiently to other interventions.

HLA-E and NKG2A Mediate Resistance to M. bovis BCG Immunotherapy in Non-Muscle-Invasive Bladder Cancer.

Mycobacterium bovis Bacillus Calmette-Guerin (BCG) is the primary treatment for non-muscle-invasive bladder cancer (NMIBC), known to stimulate inflammatory cytokines, notably interferon (IFN)-γ. We observed that prolonged IFN-γ exposure fosters adaptive resistance in recurrent tumors, aiding immune evasion and tumor proliferation. We identify HLA-E and NKG2A, part of a novel NK and T cell checkpoint pathway, as key mediators of resistance in BCG-unresponsive NMIBC. IFN-γ enhances HLA-E and PD-L1 expression in recurrent tumors, with an enrichment of intra-tumoral NKG2A-expressing NK and CD8 T cells. CXCL9+ macrophages and dendritic cells and CXCL12-expressing stromal cells likely recruit CXCR3/CXCR4-expressing NK and T cells and CXCR7+ HLA-EHIGH tumor cells. NK and CD8 T cells remain functional within BCG-unresponsive tumors but are inhibited by HLA-E and PD-L1, providing a framework for combined NKG2A and PD-L1 blockade strategy for bladder-sparing treatment of BCG-unresponsive NMIBC.

Review of Hydroxypropyl Methylcellulose in Artificial Tears for the Treatment of Dry Eye Disease.

Dry eye disease (DED) is a highly prevalent condition, resulting in reduced quality of life, lower participation in social life and impaired work efficiency. Hydroxypropyl methylcellulose (HPMC) is a cellulose-based viscosity-enhancing agent and is one of the most popular therapeutic ingredients in artificial tears. This review aims to evaluate the literature on the efficacy and safety of HPMC used in the treatment of DED. Literature searches were conducted in PubMed and Cochrane CENTRAL. A total of 28 clinical trials from 26 publications are included in this review, including 21 clinical intervention studies evaluating the effect of HPMC treatment over time and seven single instillation studies evaluating the short-term physical and symptomatic effects of HPMC after drop-instillation. The duration of clinical intervention studies ranged from 2 weeks to 5.5 months. DED severity ranged from mild to severe. Drop frequency ranged from two to up to 16 drops per day. HPMC concentration in artificial tears ranged from 0.2% to 0.5%. No major complications or adverse events were reported. Artificial tears containing HPMC were effective at improving symptoms and some signs of DED. However, combination drops with HPMC plus other therapeutic ingredients seem more effective than HPMC alone. HPMC appears to be equally effective or inferior to hyaluronic acid (HA). There is no evidence of superiority or inferiority to either carboxymethylcellulose (CMC) or polyethylene glycol 400/propylene glycol (PEG/PG). No single study explained the choice of drop frequency or HPMC concentration. More well-designed studies are needed to determine an evidence-based standard for HPMC treatment, including drop frequency, concentration and molecular weight for different DED severity and subgroups.

Long term safety and outcomes after atrial shunting for heart failure with preserved or mildly reduced ejection fraction: 5-year and 3-year follow-up in the REDUCE LAP-HF I and II trials.

BACKGROUND: There is a little evidence regarding long-term safety and efficacy for atrial shunt devices in heart failure (HF). METHODS: The REDUCE LAP-HF I (n=44) and II (n=621) trials (RCT-I and -II) were multicenter, randomized, sham-controlled trials of patients with HF and ejection fraction >40%. Outcome data were analyzed from RCT-I, a mechanistic trial with 5-year follow-up, and RCT-II, a pivotal trial identifying a responder group (n=313) defined by exercise PVR <1.74 WU and no cardiac rhythm management device with 3-year follow-up. RESULTS: At 5 years in RCT I, there were no differences in cardiovascular (CV) mortality, HF events, embolic stroke, or new-onset atrial fibrillation between groups. After 3 years in RCT II, there was no difference in the primary outcome (hierarchical composite of CV mortality, stroke, HF events, and KCCQ) between shunt and sham in the overall trial. Compared to sham, those with responder characteristics in RCT-II had a better outcome with shunt (win ratio 1.6 [95% CI 1.2-2.2], P=0.006; 44% reduction in HF events [shunt 9 vs. control 16 per 100 patient-years], P=0.005; and greater improvement in KCCQ overall summary score [+17.9±20.0 vs. +7.6±20.4], P<0.001), while non-responders had significantly more HF events. Shunt treatment at 3 years was associated with a higher rate of ischemic stroke (3.2% vs. 0%, 95% CI 2% - 6.1%, p=0.032) and lower incidence of worsening kidney dysfunction (10.7% vs. 19.3%, p=0.041). CONCLUSIONS: With up to 5 years of follow up, adverse events were low in patients receiving atrial shunts. In the responder group, atrial shunt treatment was associated with a significantly lower HF event rate and improved KCCQ compared to sham through 3 years of follow-up. CLINICALTRIALS: gov registration: NCT02600234, NCT03088033.

Safety and procedural success of daycase-based endovascular procedures in lower extremity arteries of patients with peripheral artery disease: a systematic review and meta-analysis.

Background: Timely and economic provision of revascularisation procedures is a major healthcare need. We aimed to examine the safety and efficacy of daycase-based lower extremity endovascular revascularisation procedures in patients with peripheral artery disease. Methods: In this systematic review and meta-analysis, we searched MEDLINE and Embase for studies from Jan 01, 2000 through Apr 01, 2024 reporting complications of lower limb endovascular revascularisation procedures with same-day discharge. Eligibility-criteria, complications, and patient characteristics were extracted, methodological quality assessed (adapted Newcastle-Ottawa Scale), and meta-analyses of complications and technical success performed to provide pooled estimates. This study is registered with PROSPERO, CRD42022316466. Findings: Thirty observational studies (17 retrospective, 13 prospective) and 1 RCT reported 2427 minor and 653 major complications after 99,600 daycase procedures (93,344 patients). Eighteen studies reported daycase eligibility-criteria including 'responsible adult companion' (78%), 'proximity to hospital', and 'telephone availability' and excluding unstable and severe co-morbidities, offset coagulation, and severe chronic kidney disease. Pooled incidences of minor (4.7% [95% CI 3.8-5.6%], I 2 = 96%) and major (0.64% [95% CI 0.48-0.79%], I 2  = 46%) complications were low and technical success high (93% [95% CI 91-96%], I 2 = 97%). Most complications were related to the puncture site. Pooled conversion-to-hospitalisation rates and re-admission after discharge were 1.6% (95% CI 1.1-2.2%, I 2 = 82%) and 0.11% (95% CI 0.095-0.23%, I 2 = 97%), respectively. Meta-regression identified that minor complications decreased since 2000. Male sex and coronary artery disease were associated with more frequent, and higher age and closure device use with less minor complications. Diabetes mellitus and chronic kidney disease were associated with less major complications. Six studies reported complication rates both in daycases and inpatients and there was no significant difference (-0.8% [95% CI -1.9 to 0.3%]). Interpretation: After careful evaluation of eligibility, lower limb angioplasty can be performed safely with high technical success in a daycase setting. Most complications arise from the puncture site and not the procedure itself highlighting the importance of optimal access site management. The heterogeneity between studies warrants standardised monitoring of complications and outcomes. Funding: European Partnership on Metrology, co-financed from European Union's Horizon Europe Research and Innovation Programme and UK Research and Innovation, and Medical Research Council.

Investigating synergy between beta-blockers and transarterial chemoembolization in the treatment of hepatocellular carcinoma: preliminary data from a propensity matched analysis.

PURPOSE: Favorable clinical outcomes have been reported with the adjunct use of beta-blockers in cancer treatment, hypothetically secondary to their anti-angiogenic/anti-proliferative effects. Hereby, we investigate whether there is synergy between beta-blockers and TACE in the treatment of HCC. METHODS: 36 HCC patients on beta-blockers (mean dose of 48 mg daily) at the time of first-line treatment with TACE at our institution were retrospectively identified out of a cohort of 221 patients between 2008 and 2019. Using propensity scoring, a matched cohort of 36 patients not exposed to beta-blockers was generated based on age, gender, ethnicity, etiology of liver disease, BCLC, child Pugh score, PS/ECOG, cirrhosis, largest mass treated, type of TACE and treated liver segments. Tumor response was assessed at 1st and 2nd post-TACE imaging timepoints (1.4 and 4.1 months on average respectively). Variables were compared using chi-square test and Student's t-test. Kaplan-Meier transplant-free survival plots were generated using IBM® SPSS® software. Cox regression analysis was used to evaluate survival predictors. A p values < 0.05 was considered significant. RESULTS: Comparing the control and beta-blocker cohorts, there were no differences in baseline characteristics, post-TACE imaging timepoints, tumor response or transplant free survival (p > 0.05). Tumor size was found to be a predictor of survival when the two cohorts were combined (p = 0.03). CONCLUSION: Transplant-free survival and HCC response to first-line TACE treatment were similar in the control and beta-blocker groups. Large tumor sizes were associated with higher mortality in combined analysis of the cohorts.

Antibodies and complement are key drivers of thrombosis.

Venous thromboembolism (VTE) is a common, deadly disease with an increasing incidence despite preventive efforts. Clinical observations have associated elevated antibody concentrations or antibody-based therapies with thrombotic events. However, how antibodies contribute to thrombosis is unknown. Here, we show that reduced blood flow enabled immunoglobulin M (IgM) to bind to FcµR and the polymeric immunoglobulin receptor (pIgR), initiating endothelial activation and platelet recruitment. Subsequently, the procoagulant surface of activated platelets accommodated antigen- and FcγR-independent IgG deposition. This leads to classical complement activation, setting in motion a prothrombotic vicious circle. Key elements of this mechanism were present in humans in the setting of venous stasis as well as in the dysregulated immunothrombosis of COVID-19. This antibody-driven thrombosis can be prevented by pharmacologically targeting complement. Hence, our results uncover antibodies as previously unrecognized central regulators of thrombosis. These findings carry relevance for therapeutic application of antibodies and open innovative avenues to target thrombosis without compromising hemostasis.

Swallowing during provision of helmet ventilation: Review and provisional multidisciplinary guidance.

Use of noninvasive ventilation provided by a helmet increased globally during and after the COVID-19 pandemic. This approach may reduce need for intubation and its associated clinical complications in critically ill patients. Use of helmet interface minimizes virus aerosolization while enabling verbal communication, oral feeding and coughing/expectoration of secretions during its administration. Although improved oral hydration is a recognized benefit of helmet NIV, relatively little is known about the safety and efficiency of swallowing during helmet NIV. Risk of aspiration is a key consideration given the fragile pulmonary status of critically ill patients requiring respiratory support, and therefore the decision to initiate oral intake is best made based on multidisciplinary input. We reviewed the current published evidence on NIV and its effects on upper airway physiology and swallowing function. We then presented a case example demonstrating preservation of swallowing performance with helmet NIV. Last, we offer provisional multidisciplinary guidance for clinical practice, and provide directions for future research.

Self and time in individuals with schizophrenia: A motor component?

Phenomenology suggests a disruption in the experience of time in individuals with schizophrenia, related to disorders of the sense of self. Patients themselves relate a fragmentation of their temporal experience and of their sense of self. Temporal expectations help relate the present moment to the future and we have previously shown that temporal expectations are fragile in patients, and relate to disorders of the self. Here, we investigate whether patients' performance is still impaired when the motor response to the expected event can be prepared in advance. In two different experiments participants (41 patients vs. 43 neurotypicals in total) responded to a visual target occurring at a variable interval (or "foreperiod") after an initial warning signal. Moreover, in Experiment 1 we measured the sense of self with the EASE scale. We observed the usual benefit of the passage of time: the longer the waiting period, the better the preparation, and the faster the responses. However, this effect also comprises sequential (surprise) effects, when a target occurs earlier than on the preceding trial. We evaluated the effect of the passage of time, by isolating trials that followed a trial with the same foreperiod. The benefit of long, versus short, foreperiods was still observed in controls but disappeared in patients. The results suggest that the benefit of the passage of time is diminished in patients and relates to self disorders, even when the task allows for motor preparation. The results suggest that a non-verbal impairment sub-tends disorders of the sense of self.

New and Emerging Drug and Gene Therapies for Friedreich Ataxia.

The life shortening nature of Friedreich Ataxia (FRDA) demands the search for therapies that can delay, stop or reverse its relentless trajectory. This review provides a contemporary position of drug and gene therapies for FRDA currently in phase 1 clinical trials and beyond. Despite significant scientific advances in the specificity of both compounds and targets developed and investigated, challenges remain for the advancement of treatments in a limited recruitment population. Currently therapies focus on reducing oxidative stress and improving mitochondrial function, modulating frataxin controlled metabolic pathways and gene replacement and editing. Approval of omaveloxolone, the first treatment for individuals with FRDA aged 16 years and over, has created much excitement for both those living with FRDA and those that care for them. The process of approval of omaveloxolone by the US Food and Drug Administration highlighted the importance of sensitive outcome measures and the significant role of data from natural history studies.

Melittin can permeabilize membranes via large transient pores.

Membrane active peptides are known to porate lipid bilayers, but their exact permeabilization mechanism and the structure of the nanoaggregates they form in membranes have often been difficult to determine experimentally. For many sequences at lower peptide concentrations, transient leakage is observed in experiments, suggesting the existence of transient pores. For two well-know peptides, alamethicin and melittin, we show here that molecular mechanics simulations i) can directly distinguish equilibrium poration and non-equilibrium transient leakage processes, and ii) can be used to observe the detailed pore structures and mechanism of permeabilization in both cases. Our results are in very high agreement with numerous experimental evidence for these two peptides. This suggests that molecular simulations can capture key membrane poration phenomena directly and in the future may develop to be a useful tool that can assist experimental peptide design.

Clinical Significance of Diffusion-Weighted Brain MRI Lesions After TAVR: Results of a Patient-Level Pooled Analysis.

BACKGROUND: Acute brain infarction detected by diffusion-weighted magnetic resonance imaging (DW-MRI) is common after transcatheter aortic valve replacement (TAVR), but its clinical relevance is uncertain. OBJECTIVES: The authors investigated the relationship between DW-MRI total lesion number (TLN), individual lesion volume (ILV), and total lesion volume (TLV) and clinical stroke outcomes after TAVR. METHODS: Patient-level data were pooled from 4 prospective TAVR embolic protection studies, with consistent predischarge DW-MRI acquisition and core laboratory analysis. C-statistic was used to determine the best DW-MRI measure associated with clinical stroke. RESULTS: A total of 495 of 603 patients undergoing TAVR completed the predischarge DW-MRI. At 30 days, the rate of clinical ischemic stroke was 6.9%. Acute ischemic brain injury was seen in 85% of patients with 5.5 ± 7.3 discrete lesions per patient, mean ILV of 78.2 ± 257.1 mm3, and mean TLV of 555 ± 1,039 mm3. The C-statistic was 0.84 for TLV, 0.81 for number of lesions, and 0.82 for maximum ILV in predicting ischemic stroke. On the basis of the TLV cutpoint as defined by receiver operating characteristic (ROC), patients with a TLV >500 mm3 (vs TLV ≤500 mm3) had more ischemic stroke (18.2% vs 2.3%; P < 0.0001), more disabling strokes (8.8% vs 0.9%; P < 0.0001), and less complete stroke recovery (44% vs 62.5%; P = 0.001) at 30 days. CONCLUSIONS: Our study confirms that the number, size, and total volume of acute brain infarction defined by DW-MRI are each associated with clinical ischemic strokes, disabling strokes, and worse stroke recovery in patients undergoing TAVR and may have value as surrogate outcomes in stroke prevention trials. (A Prospective, Randomized Evaluation of the TriGuard™ HDH Embolic Deflection Device During TAVI [DEFLECT III]; NCT02070731) (A Study to Evaluate the Neuro-embolic Consequences of TAVR [NeuroTAVR]; NCT02073864) (The REFLECT Trial: Cerebral Protection to Reduce Cerebral Embolic Lesions After Transcatheter Aortic Valve Implantation [REFLECT I]; NCT02536196) (The REFLECT Trial: Cerebral Protection to Reduce Cerebral Embolic Lesions After Transcatheter Aortic Valve Implantation [REFLECT II]; NCT02536196).

Effect of antidepressant treatment on 5-HT4 receptor binding and associations with clinical outcomes and verbal memory in major depressive disorder.

BACKGROUND: Brain serotonin 4 receptor (5-HT4R) levels are lower in untreated patients with Major Depressive Disorder (MDD) and are linked to verbal memory. We here investigate the relationship between 5-HT4R, clinical outcomes, and cognitive function in patients with MDD who initiate SSRI drug treatment. METHODS: Ninety moderately to severely depressed patients underwent molecular brain imaging to measure 5-HT4R binding prior to antidepressant treatment with escitalopram. Pretreatment 5-HT4R binding was assessed for its ability to predict treatment outcome at week 4, 8 or 12. In 40 patients rescanned 8 weeks post treatment, the change in cerebral 5-HT4R binding was correlated to change in verbal memory and to change in depressive symptoms, as evaluated by the Hamilton Depressive Rating Scale 6 (HAMD6). RESULTS: After 8 weeks of serotonergic intervention neostriatal 5-HT4R binding was reduced by 9%. Global change in 5-HT4R binding from baseline was associated with verbal memory outcomes, but not with overall clinical depressive symptom outcomes. Pretreatment 5-HT4R binding did not predict clinical recovery status at week 8, nor was it associated with change in HAMD6. CONCLUSIONS: In patients with moderate to severe MDD, treatment with SSRI's downregulates neostriatal 5-HT4R levels, consistent with the notion that the drugs increase cerebral extracellular serotonin. The less global brain 5-HT4R levels are downregulated after SSRIs, the more verbal memory improves, highlighting the potential importance of 5-HT4R as a treatment target in MDD. The findings offer insights to mechanisms underlying antidepressant effects and point to new directions for precision medicine treatments for MDD.

Tailored-Biomaterials Based Potential Strategies for Cardiovascular Disease.

Cardiovascular disease is a significant health concern worldwide, and varied effective treatment and prevention methods have been developed. Among these, tailored biomaterials-based strategies such as stents, scaffolds, patches, and drug delivery systems have emerged as a promising avenue. These devices are designed to match the mechanical and biological mechanisms of the cardiovascular system, ensuring optimal performance and compatibility. By effectively treating or preventing cardiovascular diseases, these devices have the potential to improve patient health outcomes significantly. They can restore blood flow by addressing blocked arteries and regenerate damaged cardiac tissue by delivering bioactive agents or cells directly to the affected area in a targeted, sustained, and controllable manner. Therefore, the objective of this article is to summarize the available evidence on these tailored biomaterial-based tunable cardiovascular devices. This knowledge can help to transform cardiovascular medicine for the treatment or prevention of cardiovascular disease and restore cardiac function to improve patients' quality of life.

Transcatheter dilation and stenting of the modified blalock-taussig shunt in cyanotic heart diseases: points to consider. A single-center experience.

Background: Our study focuses on the technique and results of interventional dilation and stenting of the modified Blalock-Taussig shunt (MBTS) performed in our center, providing a comprehensive review of our practice over the past 4 years. Methods: 42 catheter interventions on MBTS performed on 32 patients between January 2020 and May 2024 included 11 balloon dilatations and 31 stenting procedures. They were analyzed retrospectively. We documented early and late complications, the need for in-shunt reintervention or surgical revision, in-stent thrombotic events, and sudden death. Results: The median age, weight, body surface area, and procedural radiation time at the time of the intervention were 100 days (15-870 days), 5 kg (2.6-12 kg), 0.3 m2 (0.19-0.54 m2), and 12 min (7-28 min). Four interventions were performed as an emergency in three patients, of which three were performed with ECMO support. The interventions were semi-emergent for severe hypoxia in 22 patients and elective for mild desaturation in the rest. All interventions were successfully performed without any intervention-related complications or death. Eighty-two percent of the shunt dilations led to saturation improvement. Of the 31 shunt stentings performed in 26 patients, saturation improvement was documented in 97% of the cases. The late complication with stent thrombosis was documented in one patient. In two patients, sudden death and cardiac decompensation with the need for resuscitation were documented. Conclusion: MBTS interventions are effective in emergent and semi-emergent situations with severe hypoxia. While serial balloon dilatations improved the luminal diameter in clipped MBTS, most patients needed stenting as a definitive procedure. In some cases, enlargement of the shunt via stenting may be an alternative to the surgical shunt revision to accommodate the shunt size and weight and delay the subsequent operation when there are contraindications. Dual antiplatelet therapy is strongly recommended to reduce thrombotic events, especially in shunts with more than one stent and those that need reinterventions.

Off-Label Use of Peripheral Paclitaxel Drug-Coated Balloons in Management of Recurrent Coronary In-Stent Restenosis.

Background: While not available for clinical use in the United States, dedicated drug-coated balloons (DCB) are currently under investigation for the management of coronary in-stent restenosis (ISR). Peripheral drug-coated balloons (P-DCB) have been used off-label for coronary ISR. Further data regarding this practice are needed. We aimed to describe outcomes in patients who underwent off-label P-DCB angioplasty for coronary ISR. Methods: We analyzed data on P-DCB angioplasty for coronary ISR at a single high-volume center between April 1, 2015, and December 30, 2017. Demographic and procedural details were collected, with systematic follow-up as clinically indicated. Results: Data from 31 patients treated with P-DCB angioplasty (mean age 68.0 ± 10.7 years) with coronary ISR (17 recurrent and 14 first time) were analyzed. Most patients presented with high-grade angina (81%) or myocardial infarction (13%). Treated ISR lesions were in native coronary arteries (68%), saphenous vein grafts (SVG, 23%), and the left internal mammary artery (10%). Diffuse intrastent ISR was common (69%) with a mean lesion length of 21.7 ± 12.4 mm. No postprocedural myocardial infarction occurred and 1 nonprocedural mortality occurred during index admission. At follow-up (median: 283, interquartile range [IQR]: 354 days), repeat angiography was performed in 19 patients (median: 212, IQR: 188 days), and 11 patients had target lesion recurrent ISR (Kaplan-Meier event-free survival estimate: 44.7%, 95% CI, 26.1%-76.5%). Conclusions: In the absence of availability of dedicated coronary DCB, treatment of coronary ISR using P-DCB angioplasty was feasible, although follow-up demonstrated continued risk for recurrent ISR in this high-risk population.

The burden of hyperkalaemia on hospital healthcare resources.

Hyperkalaemia is associated with prolonged hospital admission and worse mortality. Hyperkalaemia may also necessitate clinical consults, therapies for hyperkalaemia and high-dependency bed utilisation. We evaluated the 'hidden' human and organisational resource utilisation for hyperkalaemia in hospitalised patients. This was a single-centre, observational cohort study (Jan 2017-Dec 2020) at a tertiary-care hospital. The CogStack system (data processing and analytics platform) was used to search unstructured and structured data from individual patient records. Association between potassium and death was modelled using cubic spline regression, adjusted for age, sex, and comorbidities. Cox proportional hazards estimated the hazard of death compared with normokalaemia (3.5-5.0 mmol/l). 129,172 patients had potassium measurements in the emergency department. Incidence of hyperkalaemia was 85.7 per 1000. There were 49,011 emergency admissions. Potassium > 6.5 mmol/L had 3.9-fold worse in-hospital mortality than normokalaemia. Chronic kidney disease was present in 21% with potassium 5-5.5 mmol/L and 54% with potassium > 6.5 mmol/L. For diabetes, it was 20% and 32%, respectively. Of those with potassium > 6.5 mmol/L, 29% had nephrology review, and 13% critical care review; in this group 22% transferred to renal wards and 8% to the critical care unit. Dialysis was used in 39% of those with peak potassium > 6.5 mmol/L. Admission hyperkalaemia and hypokalaemia were independently associated with reduced likelihood of hospital discharge. Hyperkalaemia is associated with greater in-hospital mortality and reduced likelihood of hospital discharge. It necessitated significant utilisation of nephrology and critical care consultations and greater likelihood of patient transfer to renal and critical care.