Risk of preterm birth in primiparous women with exposure to antidepressant medication before pregnancy and/or during pregnancy – impact of body mass index

Introduction: Preterm birth is a major cause of infant mortality. It is unknown whether body mass index (BMI) influences the risk of preterm birth in women, who prenatally use antidepressants.Materials and methods: The study cohort (N = 6920) consists of all primiparous European born women without previously diagnosed diabetes from the city of Vantaa, Finland, who delivered a singleton child between 2009 and 2015. Data on births, pre-pregnancy BMI and purchases of antidepressants from 12 months before conception until delivery were obtained from Finnish National Registers.Results: Of the primiparous women, 9.9% used antidepressants. The overall prevalence of preterm birth was 5.2%. In women with a pre-pregnancy BMI <18.5 kg/m², the Odds Ratio (OR) for preterm birth among antidepressant users compared with those who were non-users was 1.91 (95% confidence intervals [CI] 0.40 to 9.15, adjusted for age, smoking, education, use of fertility treatments and number of previous pregnancies) while in women with a pre-pregnancy BMI ≥30 kg/m², the OR was 0.53 (95% CI 0.21–1.36), respectively.Discussion: Primiparous women using antidepressants, who were underweight before conception should be closely monitored and provided tailored care in a maternity clinic to minimize the risk of preterm birth.

Key messages

• In primiparous women, one in ten used antidepressant medications before pregnancy and/or during pregnancy.
• In primiparous women, the prevalence of preterm birth was 5%.
• Underweight primiparous women using antidepressants should be closely monitored and provided tailored care in a maternity clinic.

     

Efficacy and safety of intravenous esmolol for cardiac protection in non-cardiac surgery. A systematic review and meta-analysis

Haemodynamic instability predisposes patients to cardiac complications in non-cardiac surgery. Esmolol, a short-acting cardioselective beta-adrenergic blocker might be efficient in perioperative cardiac protection, but could affect other vital organs, such as the kidneys, and post-discharge survival. We performed a systematic review on the use of esmolol for perioperative cardiac protection. We searched PubMed, Ovid Medline and Cochrane Central Register for Controlled trials. Eligible randomized controlled studies (RCTs) reported a perioperative esmolol intervention with at least one of the primary (major cardiac or renal complications during the first 30 postoperative days) or secondary (postoperative adverse effects and all-cause mortality) outcomes. We included 196 adult patients from three RCTs. Esmolol significantly reduced postoperative myocardial ischaemia, RR =0.43 [95% confidence interval, CI: 0.21–0.88], p = .02. No association with clinically significant bradycardia and hypotension compared to patients receiving control treatment could be confirmed (RR =7.4 [95% CI: 0.29–139.81], p = .18 and RR =2.21 [95% CI: 0.34–14.36], p = .41, respectively). No differences regarding other outcomes were observed. No study reported postoperative renal outcomes. Esmolol seems promising for the prevention of perioperative myocardial ischaemia. However, the association with bradycardia and hypotension remains unclear. Randomized trials investigating the effect of β1-selective blockade on clinically relevant outcomes and non-cardiac vital organs are warranted.

Key messages

• Short-acting cardioselective esmolol seems efficient in the prevention of perioperative myocardial ischaemia.
• The possibly increased risk of bradycardia and hypotension with short-acting intravenous beta blockade could not be confirmed or refuted by available data. Future adequately powered trials investigating the effect of β1-selective blockade on clinically relevant outcomes and non-cardiac vital organs are warranted.

     

Blood alcohol levels in Finnish victims of non-ischaemic sudden cardiac death

IntroductionNon-ischaemic heart disease (NIHD) is the underlying pathology in∼20% of all sudden cardiac deaths (SCDs). Heavy drinking is known to be associated with SCD due to ischaemic heart disease, but studies on association of recent alcohol consumption and SCD in patients with NIHD are scarce. We evaluated the blood alcohol levels of autopsy verified non-ischaemic SCD victims.MethodsStudy population was derived from the Finnish Genetic Study of Arrhythmic Events (Fingesture) (n = 5869, mean age 65 ± 12, 79% males). All deaths occurred in Northern Finland during 1998–2017. All victims underwent a medico-legal autopsy. Subjects of SCD due to ischaemic heart disease were excluded.ResultsA total of 1301 (mean age 57 ± 12, 78% males) victims of SCD due to NIHD were included in the study. The blood ethanol level was elevated in 543 (42%) subjects, out of which the blood alcohol level was ≥0.10%in 339 (62%) subjects and ≥0.15%in 252 (46%) subjects. Male SCD victims had alcohol in blood more frequently compared to females (45% versus 31%, p < .001).ConclusionElevated blood alcohol level is common in SCD victims due to NIHD, especially in males. Recent alcohol consumption might contribute to the subsequent SCD in many non-ischaemic SCD victims.

KEY MESSAGES

• Elevated blood alcohol level is common in victims of sudden cardiac death due to non-ischaemic heart disease, especially in males.
• Recent alcohol consumption may contribute to the subsequent death in many nonischemic sudden cardiac death victims.

     

Inappropriate prescribing for older people admitted to an intermediate-care nursing home unit and hospital wards

Objective

To identify inappropriate prescribing among older patients on admission to and discharge from an intermediate-care nursing home unit and hospital wards, and to compare changes during stay within and between these groups.

Design

Observational study.

Setting and subjects

Altogether 400 community-dwelling people aged ≥ 70 years, on consecutive emergency admittance to hospital wards of internal medicine and orthopaedic surgery, were randomized to an intermediate-care nursing home unit or hospital wards; 290 (157 at the intermediate-care nursing home unit and 133 in hospital wards) were eligible for this sub-study.

Main outcome measures

Prevalence on admission and discharge of potentially inappropriate medications (Norwegian general practice [NORGEP] criteria) and drug–drug interactions; changes during stay.

Results

The mean (SD) age was 84.7 (6.2) years; 71% were women. From admission to discharge, the mean numbers of drugs prescribed per person increased from 6.0 (3.3) to 9.3 (3.8), p < 0.01. The prevalence of potentially inappropriate medications increased from 24% to 35%, p < 0.01; concomitant use of ≥ 3 psychotropic/opioid drugs and drug combinations including non-steroid anti-inflammatory drugs (NSAIDs) increased significantly. Serious drug–drug interactions were scarce both on admission and discharge (0.7%).

Conclusions

Inappropriate prescribing was prevalent among older people acutely admitted to hospital, and the prevalence was not reduced during stay at an intermediate-care nursing home unit specially designed for these patients.Key Words: Acute illness, drug–drug interactions, elderly, general practice, hospital, intermediate care unit, NORGEP screening tool, Norway, potentially inappropriate medicationsOlder people are at increased risk of adverse drug events. Screening tools may identify potentially inappropriate medications. Treatment in intermediate care units may possibly provide an opportunity for reducing inappropriate prescribing.

• Inappropriate prescribing was prevalent among community-dwelling older people on emergency admittance to hospitals in Bergen, Norway.
• Concomitant use of ≥ 3 psychotropic/opioid drugs and drug combinations including non-steroid anti-inflammatory drugs (NSAIDs) increased significantly during stay.
• Serious drug–drug interactions were scarce on admission and discharge.

     

Prediction of response to cardiac resynchronization therapy using left ventricular pacing lead position and cardiovascular magnetic resonance derived wall motion patterns: a prospective cohort study

Background

Despite marked benefits in many heart failure patients, a considerable proportion of patients treated with cardiac resynchronization therapy (CRT) fail to respond appropriately. Recently, a “U-shaped” (type II) wall motion pattern identified by cardiovascular magnetic resonance (CMR) has been associated with improved CRT response compared to a homogenous (type I) wall motion pattern. There is also evidence that a left ventricular (LV) lead localized to the latest contracting LV site predicts superior response, compared to an LV lead localized remotely from the latest contracting LV site.

Methods

We prospectively evaluated patients undergoing CRT with pre-procedural CMR to determine the presence of type I and type II wall motion patterns and pre-procedural echocardiography to determine end systolic volume (ESV). We assessed the final LV lead position on post-procedural fluoroscopic images to determine whether the lead was positioned concordant to or remote from the latest contracting LV site. CRT response was defined as a ≥ 15 % reduction in ESV on a 6 month follow-up echocardiogram.

Results

The study included 33 patients meeting conventional indications for CRT with a mean New York Heart Association class of 2.8 ± 0.4 and mean LV ejection fraction of 28 ± 9 %. Overall, 55 % of patients were echocardiographic responders by ESV criteria. Patients with both a type II pattern and an LV lead concordant to the latest contracting site (T2CL) had a response rate of 92 %, compared to a response rate of 33 % for those without T2CL (p = 0.003). T2CL was the only independent predictor of response on multivariate analysis (odds ratio 18, 95 % confidence interval 1.6-206; p = 0.018). T2CL resulted in significant incremental improvement in prediction of echocardiographic response (increase in the area under the receiver operator curve from 0.69 to 0.84; p = 0.038).

Conclusions

The presence of a type II wall motion pattern on CMR and a concordant LV lead predicts superior CRT response. Improving patient selection by evaluating wall motion pattern and targeting LV lead placement may ultimately improve the response rate to CRT.     

Should pulse oximetry be included in GPs’ assessment of patients with obstructive lung disease?

Objective: To explore the associations between decreased pulse oximetry values (SpO₂) and clinical, laboratory, and demographic variables in general practice patients diagnosed with asthma or chronic obstructive pulmonary disease (COPD), including those with both COPD and asthma in combination.Design/setting: A cross-sectional study in seven Norwegian general practices of patients aged 40 years or over who were diagnosed by their general practitioner (GP) with asthma and/or COPD. The patients were examined during a stable phase of their disease. Patients diagnosed with COPD (including those with combined COPD/asthma) and those diagnosed with asthma only were analysed separately.Main outcome measures: Decreased SpO₂ values (≤ 95% and ≤ 92%).Results: Of 372 patients included (mean age 61.5 years, 62% women), 82 (22.0%) had SpO₂ ≤ 95%, of which 11 had SpO₂ ≤ 92%. In both asthma and COPD patients, SpO₂ ≤ 95% was significantly associated with reduced lung function (spirometry), a diagnosis of coronary heart disease and older age (≥ 65 years). In the COPD group, haemoglobin above normal was associated with SpO₂ ≤ 95%. These associations were confirmed by multivariable logistic regression, where FEV₁% predicted < 50 was the strongest predictor of SpO₂ ≤ 95% (odds ratio 6.8, 95% confidence interval 2.8–16.4).Conclusion. Pulse oximetry represents a useful diagnostic adjunct for assessing the severity of obstructive pulmonary disease. Decreased pulse oximetry values in stable-phase patients with asthma and/or COPD should prompt the GP to consider revising the diagnosis and treatment and to look for co-morbidities.

Key Points

• Despite its common use in general practice, the diagnostic benefits of pulse oximetry remain to be established.
• Decreased pulse oximetry values are associated with both reduced lung function (spirometry) and with a diagnosis of coronary heart disease.
• Decreased pulse oximetry values may reflect suboptimal treatment and/or undiagnosed comorbidity.
• Pulse oximetry may therefore be a useful measure in the follow-up of asthma and COPD patients in general practice.

     

A prospective evaluation of cardiovascular magnetic resonance measures of dyssynchrony in the prediction of response to cardiac resynchronization therapy

Background

Many patients with electrical dyssynchrony who undergo cardiac resynchronization therapy (CRT) do not obtain substantial benefit. Assessing mechanical dyssynchrony may improve patient selection. Results from studies using echocardiographic imaging to measure dyssynchrony have ultimately proved disappointing. We sought to evaluate cardiac motion in patients with heart failure and electrical dyssynchrony using cardiovascular magnetic resonance (CMR). We developed a framework for comparing measures of myocardial mechanics and evaluated how well they predicted response to CRT.

Methods

CMR was performed at 1.5 Tesla prior to CRT. Steady-state free precession (SSFP) cine images and complementary modulation of magnetization (CSPAMM) tagged cine images were acquired. Images were processed using a novel framework to extract regional ventricular volume-change, thickening and deformation fields (strain). A systolic dyssynchrony index (SDI) for all parameters within a 16-segment model of the ventricle was computed with high SDI denoting more dyssynchrony. Once identified, the optimal measure was applied to a second patient population to determine its utility as a predictor of CRT response compared to current accepted predictors (QRS duration, LBBB morphology and scar burden).

Results

Forty-four patients were recruited in the first phase (91% male, 63.3 ± 14.1 years; 80% NYHA class III) with mean QRSd 154 ± 24 ms. Twenty-one out of 44 (48%) patients showed reverse remodelling (RR) with a decrease in end systolic volume (ESV) ≥ 15% at 6 months. Volume-change SDI was the strongest predictor of RR (PR 5.67; 95% CI 1.95-16.5; P = 0.003). SDI derived from myocardial strain was least predictive. Volume-change SDI was applied as a predictor of RR to a second population of 50 patients (70% male, mean age 68.6 ± 12.2 years, 76% NYHA class III) with mean QRSd 146 ± 21 ms. When compared to QRSd, LBBB morphology and scar burden, volume-change SDI was the only statistically significant predictor of RR in this group.

Conclusion

A systolic dyssynchrony index derived from volume-change is a highly reproducible measurement that can be derived from routinely acquired SSFP cine images and predicts RR following CRT whilst an SDI of regional strain does not.     

Relationship between mechanical dyssynchrony and intra-operative electrical delay times in patients undergoing cardiac resynchronization therapy

Background

It is important to understand the relationship between electrical and mechanical ventricular activation in CRT patients. By measuring local electrical activation at multiple locations within the coronary veins and myocardial contraction at the same locations in the left ventricle, we determined the relationship between electrical and mechanical activation at potential left ventricular pacing locations.

Methods

In this study, mechanical contraction times were computed using high temporal resolution cine cardiovascular magnetic resonance (CMR) data, while electrical activation times were derived from intra-procedural local electrograms.

Results

In our cohort, there was a strong correlation between electrical and mechanical delay times within each patient (R² = 0.78 ± 0.23). Additionally, the latest electrically activated location corresponded with the latest mechanically contracting location in 91% of patients.

Conclusions

This study provides initial evidence that our method of obtaining non-invasive mechanical activation patterns accurately reflects the underlying electromechanical substrate of intraventricular dyssynchrony.     

Right ventricular dysfunction is a predictor of non-response and clinical outcome following cardiac resynchronization therapy

Background

Cardiac resynchronization therapy (CRT) is an established treatment in advanced heart failure (HF). However, an important subset does not derive a significant benefit. Despite an established predictive role in HF, the significance of right ventricular (RV) dysfunction in predicting clinical benefit from CRT remains unclear. We investigated the role of RV function, assessed by cardiovascular magnetic resonance (CMR), in predicting response to and major adverse clinical events in HF patients undergoing CRT.

Methods

Sixty consecutive patients were evaluated with CMR prior to CRT implantation in a tertiary cardiac centre. The primary end-point was a composite of death from any cause or unplanned hospitalization for a major cardiovascular event. The secondary end-point was response to therapy, defined as improvement in left ventricular ejection fraction ≥ 5% on echocardiography at one year.

Results

Eighteen patients (30%) met the primary end-point over a median follow-up period of 26 months, and 27 out of 56 patients (48%) were considered responders to CRT. On time-to-event analysis, only atrial fibrillation (HR 2.6, 95% CI 1.02-6.84, p = 0.047) and RV dysfunction, either by a reduced right ventricular ejection fraction-RVEF (HR 0.96, 95% CI 0.94-0.99, p = 0.006) or tricuspid annular plane systolic excursion-TAPSE (HR 0.88, 95% CI, 0.80-0.96, p = 0.006), were significant predictors of adverse events. On logistic regression analysis, preserved RVEF (OR 1.05, 95% CI 1.01-1.09, p = 0.01) and myocardial scar burden (OR 0.90, 95% CI 0.83-0.96, p = 0.004) were the sole independent predictors of response to CRT. Patients with marked RV dysfunction (RVEF < 30%) had a particularly low response rate (18.2%) to CRT.

Conclusions

Right ventricular function is an important predictor of both response to CRT and long-term clinical outcome. Routine assessment of the right ventricle should be considered in the evaluation of patients for CRT.     

Evidence for electrical remodeling of the native conduction system with cardiac resynchronization therapy

BACKGROUND: Cardiac resynchronization therapy (CRT) improves hemodynamics and decreases heart failure symptoms. However, the potential of CRT to bring about electrical remodeling of the heart has not been investigated. METHODS AND RESULTS: We studied 25 patients, of whom 17 had a nonischemic cardiomyopathy, and 8 had an ischemic cardiomyopathy; 16 had left bundle branch block (LBBB), 1 right bundle branch block (RBBB), and 8 nonspecific intraventricular conduction delay. During routine device clinic visits, patients with chronic biventricular pacing (>6 months) were reprogrammed to VVI 40 to allow for native conduction to resume. After 5 minutes of native rhythm, a surface electrocardiogram (ECG) was recorded, and then the previous device settings were restored. This ECG was compared to the preimplant ECG. Preimplant mean ejection fraction was 19% (range, 10%-35%), and follow-up mean ejection fraction was 35% (12.5%-65%). Mean time from implant to follow-up ECG was 14 months (range, 6-31). The QRS interval prior to CRT was 155 +/- 29 ms, and shortened to 144 +/- 31 ms (P = 0.0006), and the QRS axis shifted from -1 +/- 59 to -26 +/- 53 (P = 0.03). There was no significant change in PR or QTc interval, or in heart rate. CONCLUSION: CRT leads to a decrease in the surface QRS duration, without affecting other surface ECG parameters. The reduced electrical activation time may reflect changes in the specialized conduction system or in intramyocardial impulse transmission.     

Clinical implications of cardiac troponin-I in patients with hypertensive crisis visiting the emergency department

ObjectivesCardiac troponin-I (cTnI) is a representative marker of myocardial injury. Elevation of cTnI is frequently observed in patients with hypertensive crisis, but few studies have examined its prognostic significance in hypertensive crisis. We aimed to determine whether cTnI could predict all-cause mortality in patients with hypertensive crisis visiting the emergency department (ED).MethodsThis observational study included patients aged ≥18 years who visited an ED between 2016 and 2019 for hypertensive crisis, defined as systolic blood pressure (BP) ≥180 mmHg and/or diastolic BP ≥110 mmHg. Among 6467 patients, 3938 who underwent a cTnI assay were analysed.ResultsAmong the 3938 patients, 596 (15.1%) had cTnI levels above the 99th percentile upper reference limit (elevated cTnI >40 ng/L) and 600 (15.2%) had cTnI levels between the detection limit (≥10 ng/L) and the 99th percentile upper reference limit (detectable cTnI). The 3-year all-cause mortality in the elevated, detectable and undetectable cTnI groups were 41.6%, 36.5% and 12.8%, respectively. After adjusting for confounding variables, elevated cTnI patients (adjusted hazard ratio [HR], 2.01; 95% confidence interval [CI], 1.61–2.52) and detectable cTnI patients (adjusted HR, 1.64; 95% CI, 1.32–2.04) showed a significantly higher risk of 3-year all-cause mortality than did patients with undetectable cTnI.ConclusionsIn patients with hypertensive crisis, elevated cTnI levels provide useful prognostic information and permit the early identification of patients with an increased risk of death. Moreover, putatively normal but detectable cTnI levels also significantly correlated with a higher risk of all-cause mortality. Intensive treatment and follow-up strategies are needed for patients with hypertensive crisis with elevated and detectable cTnI levels.

Key messages

1. Cardiac troponin-I level was an independent prognostic factor for all-cause mortality in patients with hypertensive crisis.
2. Detectable but normal range cardiac troponin-I, which was considered clinically insignificant, also had a prognostic impact on all-cause mortality comparable to elevated cardiac troponin-I levels.

     

Variability in the leptin receptor gene and other risk factors for post-transplant diabetes mellitus in renal transplant recipients

Aim: Post-transplant diabetes mellitus (PTDM) is one of the main complications after kidney transplantation. It is known that leptin plays an important role in glucose metabolism and mutations in the leptin receptor gene (LEPR) are responsible for different complications in renal transplant recipients. We aimed to analyse the association of polymorphisms in LEPR with the development of PTDM in these patients.Methods: A total of 315 renal transplant recipients were genotyped for the Lys109Arg, Gln223Arg and Lys656Asn polymorphisms. The impact of these genetic variables together with other clinical and demographic parameters on PTDM risk was evaluated in a multivariate regression analysis.Results: The 223Arg variant showed a significant association with PTDM risk [OR = 3.26 (1.35–7.85), p = 0.009] after correcting for multiple testing. Carriers of this variant also showed higher BMI values (26.95 ± 4.23) than non-carriers (25.67 ± 4.43, p = 0.025). In addition, it was BMI at transplant and not the BMI increment in the first year after grafting that was associated with PTDM (p > 0.00001). Haplotype analyses did not reveal significant associations.Conclusions: Our result show, for the first time to our knowledge, that genetic variability in the LEPR may contribute significantly to the risk for PTDM in renal transplant recipients.

KEY MESSAGES

• The LEPR Gln223Arg polymorphism significantly contributes to the development of PTDM in renal transplant recipients.
• The effect of the 223Arg variant on PTDM is strongly modulated by the age of the recipient.
• The 223Arg variant in the leptin receptor is related to higher BMI in renal transplant recipients.

     

Extensive phenotype data and machine learning in prediction of mortality in acute coronary syndrome – the MADDEC study

Objective: Investigation of the clinical potential of extensive phenotype data and machine learning (ML) in the prediction of mortality in acute coronary syndrome (ACS).Methods: The value of ML and extensive clinical data was analyzed in a retrospective registry study of 9066 consecutive ACS patients (January 2007 to October 2017). Main outcome was six-month mortality. Prediction models were developed using two ML methods, logistic regression and extreme gradient boosting (xgboost). The models were fitted in training set of patients treated in 2007–2014 and 2017 (81%, n = 7344) and validated in a separate validation set of patients treated in 2015–2016 with full GRACE score data available for comparison of model accuracy (19%, n = 1722).Results: Overall, six-month mortality was 7.3% (n = 660). Several variables were found to be significantly associated with six-month mortality by both ML methods. The xgboost scored the best performance: AUC 0.890 (0.864–0.916). The AUC values for logistic regression and GRACE score were 0.867(0.837–0.897) and 0.822 (0.785–0.859), respectively. The AUC value of xgboost was better when compared to logistic regression (p = .012) and GRACE score (p < .00001).Conclusions: The use of extensive phenotype data and novel machine learning improves prediction of mortality in ACS over traditional GRACE score.

KEY MESSAGES

• The collection of extensive cardiovascular phenotype data from electronic health records as well as from data recorded by physicians can be used highly effectively in prediction of mortality after acute coronary syndrome.
• Supervised machine learning methods such as logistic regression and extreme gradient boosting using extensive phenotype data significantly outperform conventional risk assessment by the current golden standard GRACE score.
• Integration of electronic health records and the use of supervised machine learning methods can be easily applied in a single centre level to model the risk of mortality.

     

Does C-reactive protein predict time to recovery and benefit from oseltamivir treatment in primary care patients with influenza-like illness? A randomized controlled trial secondary analysis

ObjectiveRecovery time and treatment effect of oseltamivir in influenza-like illness (ILI) differs between patient groups. A point-of-care test to better predict ILI duration and identify patients who are most likely to benefit from oseltamivir treatment would aid prescribing decisions in primary care. This study aimed to investigate whether a C-reactive protein (CRP) concentration of ≥30 mg/L can predict (1) ILI disease duration, and (2) which patients are most likely to benefit from oseltamivir treatment.DesignSecondary analysis of randomized controlled trial data.SettingPrimary care in Lithuania, Sweden and Norway during three consecutive influenza seasons 2016–2018.SubjectsA total of 277 ILI patients aged one year or older and symptom duration of ≤72 h.Main outcome measuresCapillary blood CRP concentration at baseline, and ILI recovery time defined as having ‘returned to usual daily activity’ with residual symptoms minimally interfering.ResultsAt baseline, 20% (55/277) had CRP concentrations ≥30mg/L (range 0–210). CRP concentration ≥30 mg/L was not associated with recovery time (adjusted hazards ratio (HR) 0.80: 95% CI 0.50–1.3; p = 0.33). Interaction analysis of CRP concentration ≥30 mg/L and oseltamivir treatment did not identify which patients benefit more from oseltamivir treatment (adjusted HR 0.69: 95% CI 0.37–1.3; p = 0.23).ConclusionThere was no association between CRP concentration of ≥30 mg/L and recovery time from ILI. Furthermore, CRP could not predict which ILI patients benefit more from oseltamivir treatment. Hence, we do not recommend CRP testing for predicting ILI recovery time or identifying patients who will receive particular benefit from oseltamivir treatment.

Key Points

• Predicting disease course of influenza-like illness (ILI), and identifying which patients benefit from oseltamivir treatment is a challenge for physicians.
• • There was no association between CRP concentration at baseline and recovery time in patients consulting with ILI in primary care.
• • There was no association between CRP concentration at baseline and benefit from oseltamivir treatment.
• • We, therefore, do not recommend CRP testing for predicting recovery time or in decision-making concerning oseltamivir prescribing in ILI patients.

     

Identification of novel variants in ten patients with Hermansky-Pudlak syndrome by high-throughput sequencing

Background: Hermansky-Pudlak syndrome (HPS) is a rare inherited platelet disorder characterized by bleeding diathesis, oculocutaneous albinism (OCA) and a myriad of often-serious clinical complications.Methods: We established the clinical and laboratory phenotype and genotype of six unrelated pedigrees comprising ten patients with clinical suspicion of HPS; including platelet aggregation, flow cytometry, platelet dense granule content, electron microscopy and high-throughput sequencing (HTS).Results: The clinical presentation showed significant heterogeneity and no clear phenotype-genotype correlations. HTS revealed two known and three novel disease-causing variants. The Spanish patients carried a homozygous p.Pro685Leufs17* deletion (n = 2) in HPS4, or the novel p.Arg822* homozygous variant (n = 1) in HPS3. In the case of two Turkish sisters, a novel missense homozygous HPS4 variant (p.Leu91Pro) was found. In two Portuguese families, genetic studies confirmed a previously reported nonsense variant (p.Gln103*) in DTNBP1 in three patients and a novel duplication (p.Leu22Argfs*33) in HPS6 in two unrelated patients.Conclusions: Our findings expand the mutational spectrum of HPS, which may help in investigating phenotype-genotype relationships and assist genetic counselling for affected individuals. This approach is a proof of principle that HTS can be considered and used in the first-line diagnosis of patients with biological and clinical manifestations suggestive of HPS.

Key messages

• We established the relationships between the clinical and laboratory phenotype and genotype of six unrelated pedigrees comprising ten patients with clinical suspicion of HPS.
• Molecular analysis is useful in confirming the diagnosis and may offer some prognostic information that will aid in optimizing monitoring and surveillance for early detection of end-organ damage.
• This approach is a proof of principle that HTS can be considered and used in the first-line diagnosis of patients with biological and clinical manifestations suggestive of HPS.

     

The clinical features and outcomes of systemic light chain amyloidosis with hepatic involvement

ObjectivesTo evaluate the clinical characteristics and prognostic factors of hepatic systemic light chain (AL) amyloidosis.MethodsEighty-eight patients diagnosed AL amyloidosis with hepatic involvement between June 2004 and January 2019 were analysed retrospectively.ResultsThe median age of the patients was 55 years old, and the male to female ratio was 2.8:1.The main clinical manifestations include edema, digestive symptoms, weight loss, fatigue and ascites. Fifty-one patients received treatment, 42 patients were suitable for therapeutic efficacy evaluation and 25 (59.5%) achieved haematologic response. The median survival time was nine months, and the survival rates at one year, three years and five years were 33.0%, 11.4% and 6.8%, respectively. The risk of death was 6.6 times that of those who did not achieve haematologic response. Multivariate analysis showed that baseline NT-proBNP ≥ 1800 pg/ml and total bilirubin ≥ 34.2 umol/L were predictive of all-cause death.ConclusionsSystemic light chain amyloidosis with hepatic involvement is associated with poor survival but rarely has specific manifestations. The significant increase of NT-proBNP and hyperbilirubinemia indicate a poor prognosis. Vigilance should be raised to the relevant clinical manifestations, early diagnosis and timely treatment can improve the prognosis.

KEY MESSAGES

• Systemic light chain amyloidosis with hepatic involvement is associated with poor survival but rarely has specific manifestations.
• The significant increase of NT-proBNP and hyperbilirubinemia indicate a poor prognosis.

     

Predictive value of sub classification of focal segmental glomerular sclerosis in Oxford classification of IgA nephropathy

BackgroundThe Oxford classification of IgA nephropathy (IgAN) was revised in 2016 which lacked sufficient evidence for prognostic value of subclassification of focal segmental glomerular sclerosis (S lesion), and the proper proportion of S lesion for subclassification remains undetermined.AimThis study aimed to explore the predictive value of the new subclassification of S score on renal outcomes of IgAN patients.Methods348 patients with IgAN-associated S lesion were enrolled. According to the optimal cut-off of 25% established by receiver operating characteristic (ROC) curves, we divided S1 patients into two groups: S1a group (S lesion < 25%) and S1b group (S lesion ≥ 25%). IgAN patients with mild lesion (M0E0S0T0C0) were set as the control group. The clinical features at renal biopsy, pathological findings, and follow-up parameters (follow-up time ranged from 1 to 5 years) were collected. We used univariate and multivariate analyses to assess whether the subclassification of S score could refine risk prediction and clinical utility.ResultsWe demonstrated that S lesion ≥ 25% was associated with a more rapid GFR loss and a lower rate of complete remission of proteinuria even adjusted for multiple clinic pathological variables, compared to S1a group (All p values <.05). And the ratio of glomeruli with T lesion and crescents were higher in patients with S lesion ≥ 25%. Data showed that IgAN patients with S lesion ≥ 25% were at an increased risk of poor renal outcomes even with immunosuppression.ConclusionThis study might recommend new subclassification of S scores (S0 (no S lesion), S1 (S lesion <25% of glomeruli), and S2 (S lesion ≥ 25% of glomeruli)) for the Oxford classification. This model may also help to evaluate pros and cons of immunosuppressive therapy in IgAN patients with different level of S lesion.

KEY MESSAGES

• S lesion ≥ 25% is an independent risk factor for poor renal outcome in IgAN patients.
• This new subclassification of S scores may help to evaluate pros and cons of immunotherapy in IgAN patients with different level of S lesion.