SGLT2 inhibitors for patients with type 2 diabetes mellitus after myocardial infarction: a nationwide observation registry study from SWEDEHEART.

Background: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to reduce rates of heart failure hospitalisations and cardiovascular death in patients with type 2 diabetes and prior cardiovascular disease. We hypothesised that SGLT2 inhibitors could provide cardiovascular benefits in the post-myocardial infarction setting. We aimed to investigate cardiovascular outcomes of SGLT2 inhibitor therapy in patients with type 2 diabetes mellitus after myocardial infarction in a Swedish nationwide registry. Methods: We included all patients with type 2 diabetes surviving a type 1 acute myocardial infarction from January 1, 2018 to December 31, 2021. Patients were included if they were discharged with an estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m2 in the nationwide Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) registry. We identified all patients discharged with or without an SGLT2 inhibitor prescription 120 days before or within three days after discharge from the cardiac care unit. The primary outcome measure was a composite of death and first hospitalisation for heart failure after one year analysed using an adjusted Cox regression. Findings: A total of 11,271 patients were included. Of these, 2498 (22.2%) received SGLT2 inhibitor treatment. Patients who were prescribed SGLT2 inhibitors were younger, more often presented with a STEMI and had worse left ventricular ejection fraction at index hospitalisation. SGLT2 inhibitor use was associated with lower rates of the composite outcome (hazard ratio (HR) of 0.70 (95% confidence interval (CI) 0.59-0.82). Interpretation: Treatment with SGLT2 inhibitors after myocardial infarction in patients with type 2 diabetes was associated with a lower rate of cardiovascular events. Funding: This work was supported by Hjärt-Lungfonden, Vetenskapsrådet, Knut and Alice Wallenberg Foundation, ALF, the Bundy Academy, and Skåne University Hospital funds.

Neurofilament light chain as a diagnostic and prognostic biomarker in Guillain-Barré syndrome.

BACKGROUND: Elevated neurofilament light chain (NfL) levels are associated with worse prognosis in Guillain-Barré syndrome (GBS). Our objectives were to determine the utility of serum NfL (sNfL), cerebrospinal fluid (CSF)/serum NfL ratio and NfL index as prognostic and diagnostic biomarkers for GBS. METHODS: We measured NfL in serum and/or CSF obtained from 96 GBS patients between 1989 and 2014 in western Sweden. The sNfL Z-scores, NfL ratios and NfL indices were calculated. Outcome was determined with the GBS disability scale (GBSDS) at 3 and 12 months. NfL parameters in GBS were compared with healthy controls (HC), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). RESULTS: The sNfL Z-score was higher for GBSDS > 2 at 3 months (median [IQR], 3.5 ng/L [3.2-4.0], vs 2.6 [1.7-3.4], p = 0.008) and at 12 months (3.6 ng/L [3.5-3.8] vs 2.6 [1.8-3.5], p = 0.049). NfL ratio and index were not associated with outcome. The area under the curve (AUC) for sNfL Z-score was 0.76 (95% CI 0.58-0.93, p < 0.0001) for GBSDS > 2 at 3 months. NfL ratio and index were lower in GBS than HC, MS, and ALS. The AUC for the NfL ratio was 0.66 (95% CI 0.55-0.78, p = 0.0018) and for the NfL index 0.86 (95% CI 0.78-0.93, p < 0.0001). DISCUSSION: Our results confirm sNfL as prognostic biomarker for GBS and the precision was improved using the age-adjusted sNfL Z score. NfL index and Qalb are potential diagnostic biomarkers for GBS.

High levels of neurofilament light and YKL-40 in cerebrospinal fluid are related to poor outcome in ALS.

Amyotrophic lateral sclerosis (ALS) is a neurological disease without effective treatment. No pathognomonic test can diagnose ALS in sporadic cases. Routine investigation in suspected cases includes neurological examination, imaging of the brain and spine and electromyography supported by blood and cerebrospinal fluid (CSF) analyses. The ALS diagnosis is made by clinical judgement and results from examinations. We aimed to study if the CSF biomarkers neurofilament light protein (NFL), glial fibrillary acidic protein (GFAP), YKL-40, soluble amyloid precursor protein (sAPP) α and ß, and soluble triggering receptor expressed on myeloid cells 2 (sTREM2) were associated with ALS diagnosis and could predict disease progression. Eighty-one patients with suspected ALS were included after referral to the neurological clinic at Sahlgrenska University Hospital. Fifty-nine patients were diagnosed having ALS, while 22 patients were given alternative diagnoses and labeled ALS mimics. Finally, 25 age-matched neurologically intact individuals were used as controls. ALS patients had significantly higher CSF levels of NFL than controls and mimics. Levels of YKL-40 and GFAP were significantly higher in ALS patients compared with controls. No difference was found between study groups when comparing levels of sAPPα, sAPPß and sTREM2. Further, elevated levels of NFL and YKL-40 were associated with an increased hazard of death and the annual decline in ALSFRS-R. We also found that patients with elevated levels of both NFL and YKL-40 had a particularly poor prognosis. The results demonstrate the usefulness of CSF biomarkers in the diagnosis and prognostication of ALS.

Coronary Artery Lesion Lipid Content and Plaque Burden in Diabetic and Nondiabetic Patients: PROSPECT II.

BACKGROUND: Patients with diabetes have increased rates of major adverse cardiac events (MACEs). We hypothesized that this is explained by diabetes-associated differences in coronary plaque morphology and lipid content. METHODS: In PROSPECT II (Providing Regional Observations to Study Predictors of Events in the Coronary Tree), 898 patients with acute myocardial infarction with or without ST-segment elevation underwent 3-vessel quantitative coronary angiography and coregistered near-infrared spectroscopy and intravascular ultrasound imaging after successful percutaneous coronary intervention. Subsequent MACEs were adjudicated to either treated culprit lesions or untreated nonculprit lesions. This substudy stratified patients by diabetes status and assessed baseline culprit and nonculprit prevalence of high-risk plaque characteristics defined as maximum plaque burden ≥70% and maximum lipid core burden index ≥324.7. Separate covariate-adjusted multivariable models were performed to identify whether diabetes was associated with nonculprit lesion-related MACEs and high-risk plaque characteristics. RESULTS: Diabetes was present in 109 of 898 patients (12.1%). During a median 3.7-year follow-up, MACEs occurred more frequently in patients with versus without diabetes (20.1% versus 13.5% [odds ratio (OR), 1.94 (95% CI, 1.14-3.30)]), primarily attributable to increased risk of myocardial infarction related to culprit lesion restenosis (4.3% versus 1.1% [OR, 3.78 (95% CI, 1.12-12.77)]) and nonculprit lesion-related spontaneous myocardial infarction (9.3% versus 3.8% [OR, 2.74 (95% CI, 1.25-6.04)]). However, baseline prevalence of high-risk plaque characteristics was similar for patients with versus without diabetes concerning culprit (maximum plaque burden ≥70%: 90% versus 93%, P=0.34; maximum lipid core burden index ≥324.7: 66% versus 70%, P=0.49) and nonculprit lesions (maximum plaque burden ≥70%: 23% versus 22%, P=0.37; maximum lipid core burden index ≥324.7: 26% versus 24%, P=0.47). In multivariable models, diabetes was associated with MACEs in nonculprit lesions (adjusted OR, 2.47 [95% CI, 1.21-5.04]) but not with prevalence of high-risk plaque characteristics (adjusted OR, 1.21 [95% CI, 0.86-1.69]). CONCLUSIONS: Among patients with recent myocardial infarction, both treated and untreated lesions contributed to the diabetes-associated ≈2-fold increased MACE rate during the 3.7-year follow-up. Diabetes-related plaque characteristics that might underlie this increased risk were not identified by multimodality imaging. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02171065.

Life after cardiac arrest: A very long term follow up.

AIM: To describe survival and causes of death after cardiac arrest (CA) and the life situation of very long term survivors. METHODS: Individuals with successful resuscitation treated at the Sahlgrenska university hospital during 1995-1999 and presented in former CA publications were studied. Survival time and causes of death data were extracted from the individuals who had died's records. Very long term survivors were offered a follow up visit at home. Mini Mental State Examination (MMSE) used to describe cognitive abilities and EQ-5D to assess quality of life. The life situation was also explored. RESULTS: 14 out of 104 possible participants had survived to follow up. The median time to follow up among the 8 who agreed to participation was 17 years. Out of the 8 participants, 4 failed to reach the cut off score of normal cognitive abilities in the MMSE and 7/8 participants did not reach the cut off score for normal cognitive function in the MoCA. Overall the participants were content with their life situation and QoL. However, a tendency towards lower scores on the cognitive testing and a lower self-reported QoL was observed. No depression, post-traumatic stress disorder or anxiety disorder were found. CONCLUSIONS: A CA may lead to permanent cognitive impairments and the risk of dementia may be higher because of the injuries sustained during the collapse. However, further studies with more participants are needed to fully determine the risk of cognitive impairment after a CA. Regarding life situation, there was a tendency of lower QoL with lower scores on the cognitive testing. With a new treatment paradigm, there is a need for long term studies regarding this new population.

Cerebrospinal fluid biomarkers in cardiac arrest survivors.

AIM: The aim of this study was to investigate the levels of various cerebrospinal fluid (CSF) biomarkers related to neuronal damage, inflammation and amyloid ß (Aß) metabolism in patients resuscitated after an out-of-hospital cardiac arrest (CA). METHODS: CSF levels of neurofilament light protein (NFL), total tau (T-tau), hyperphosphorylated tau (P-tau), YKL-40, Aß38, Aß40, Aß42, soluble amyloid precursor protein α and ß (sAPPα and sAPPß) were measured in 21 patients approximately two weeks after CA and in 21 age-matched neurologically healthy controls. The biomarker levels were also compared between patients with good and poor long-term clinical outcome according to Glasgow Outcome Scale (GOS), activities of daily living (ADL) and mini-mental state examination (MMSE), measuring neurologic function, daily functioning and cognitive function, respectively. RESULTS: Patients with CA had a very marked increase in the CSF levels of NFL, T-tau and YKL-40 as compared with controls. The levels were increased at about 1200, 700 and 100%, respectively. NFL and T-tau were significantly higher in patients with poor outcome according to all three outcome measures. Patients with poor outcome according to GOS and ADL had higher levels of YKL-40. Levels of Aß38, Aß40, Aß42, sAPPα and sAPPß were lower in patients with a low MMSE score. P-tau was not significantly altered. CONCLUSIONS: Biomarkers reflecting neuronal damage and inflammation, but not so much Aß metabolism, were significantly altered in patients after a CA, and the changes were more pronounced in the groups with poor outcome. This calls for future larger studies to determine the prognostic potential of these biomarkers.

Autograft versus interbody fusion cage without plate fixation in the cervical spine: a randomized clinical study using radiostereometry.

A primary object with a fusion cage is avoidance of graft collapse with subsequent subsidence and malalignment of the cervical spine that is observed after bone grafting alone. No randomized studies exist that demonstrate the difference between these two methods in terms of graft subsidence and angulation of the fused segment. The size of the study population was calculated to be 24 patients to reach a significant difference at the 95% CI level. Patients with one-level cervical radiculopathy scheduled for surgery were randomized to anterior discectomy and fusion (ACDF) with autograft or to fusion cage, both without plate fixation. Tantalum markers were inserted in the two adjacent vertebrae at the end of surgery. Radiostereometry was performed immediately postoperatively and at regular intervals for 2 years. Questionnaires were used to evaluate the clinical outcome and an unbiased observer graded the outcome after 2 years. No significant differences were found between the two methods after 2 years in regard of narrowing of the disc space (mean 1.7 and 1.4 mm, respectively) or deformation of the fused segment into flexion (mean 7.7 degrees and 4.6 degrees , respectively). Patients in the cage group had a significantly better clinical outcome. The findings of subsidence and flexion deformation of the fused segment after 2 years seem to be of no clinical importance after one-level cervical disc surgery. However, in multi-level surgery using the same methods, an additive effect of the deformations of the fused segments may affect the clinical outcome.

The first year after successful cardiac resuscitation: function, activity, participation and quality of life.

AIM: To assess cognitive function, activities of daily living (ADL) and living situation longitudinally up to 1 year after cardiac arrest. SETTING: University hospital. MATERIALS: The study continued for 3 years and consecutive patients (18-75 years of age) who survived resuscitation were included. METHOD: A longitudinal study with examinations using the National Institute of Health Stroke Scale for assessing brain damage, along with the Mini Mental State Examination. To assess ADL, we used the Functional Independence Measure and the Instrumental Activity Measure. Life satisfaction was assessed, together with health-related quality of life. Social status and vocational status were recorded. RESULTS: Mortality was high during the first 90 days (31%). After discharge, not much improvement was seen in cognitive function. This was reflected in reduced dependency in ADL. Work capacity at 1 year was only 13%. The health related quality of life showed great improvement during the first year, being almost the same as for Swedish reference values. CONCLUSIONS: Most of the improvement resulting in the independence of ADL occurred during the first 45 days. It is important to give the next of kin information about the patient's progress and need for assistance in order to enable them to plan for the future before discharge.