Prior Diagnosis Research Articles

Incidence and predictors of heart failure events following cardiac surgery in patients with atrial fibrillation - insights from the LAAOS-III trial

Abstract Background Atrial fibrillation (AF) is a common comorbidity in patients undergoing cardiac surgery and further increases the risk of incident heart failure (HF). However, only limited data exist on HF events following surgery in patients with AF. Methods The Left Atrial Appendage Occlusion Study (LAAOS) III was a randomized trial evaluating concomitant left atrial appendage occlusion in patients with AF undergoing cardiac surgery. In this secondary analysis, we aimed to identify independent predictors of the composite outcome of HF hospitalization or HF-related death following discharge, using a multivariable Cox model – incorporating sex, age (≥65 vs <65 years), systolic blood pressure (≤140 vs >140 mmHg), body mass index (BMI; <25 vs 25-29.9 vs ≥30 kg/m2), diabetes mellitus (DM), prior HF diagnosis, prior stroke, ischemic heart disease (IHD), heart valve surgery, AF history duration, rhythm on discharge electrocardiogram, and trial allocation. Supplementary analyses were undertaken to further assess the continuous variables using cubic spline regression. Results Of 4770 patients enrolled, in-hospital death occurred in 201 (4.2%) and complete discharge data were available for 4564 (95.7%). During a median follow up of 3.9 years, 533 (11.7%) of 4564 patients were hospitalized for HF. In total, 873 (19.1%) died after discharge, including 95 HF-related deaths. The composite outcome of HF hospitalization or HF-related death occurred at an annualized event rate of 3.31%/year [95% confidence interval: 3.04-3.60]. The independent risk factors included age (event rate of 3.64%/year vs 2.03%/year for ≥65 vs <65 years; hazard ratio (HR) 1.71 [1.32-2.21]), DM (4.71%/year vs 2.71%/year for with vs without DM; HR 1.59 [1.34-1.90]), prior HF diagnosis (4.27%/year vs 2.17%/year for with vs without HF; HR 2.00 [1.66-2.41]), IHD (3.63%/year vs 2.85%/year for with vs without IHD; HR 1.26 [1.03-1.54]), AF history duration (3.81%/year vs 2.89%/year for >2 vs <0.5 years; HR 1.23 [1.01-1.50]), and AF rhythm at discharge (3.87%/year vs 2.68%/year for AF vs non-AF rhythm; HR 1.31 [1.09-1.58]). The supplementary spline analyses further revealed a positive correlation between BMI and the risk of the composite outcome (p-value 0.042). Conclusions In patients with AF undergoing cardiac surgery, post-discharge HF hospitalization and HF-related death occurred at a rate of 3.31% per year. Our study identified several significant risk factors including advanced age, higher BMI, DM, prior HF diagnosis, IHD, AF history >2 years, and AF rhythm at discharge.The associations of HF with age and BMI

Feasibility and diagnostic yield of a photoplethysmography-based arrhythmia screening and integrated management pathway in a chronic obstructive pulmonary disease outpatient clinic

Abstract Background Guidelines recommend opportunistic screening for atrial fibrillation (AF) in high-risk populations, including chronic obstructive pulmonary disease (COPD) patients. Purpose We aimed to assess the feasibility and yield of a photoplethysmography (PPG) smartphone app-based pathway for AF detection within a COPD outpatient clinic. Methods Ninety-nine eligible patients from the COPD outpatient clinic at the Maastricht University Medical Center+ underwent a 14-days PPG app-based AF screening. PPG-based AF detection triggered an electrocardiogram (ECG) for AF diagnosis and initiation of a comprehensive AF management. Patients’ adherence and system usability were assessed. Results Patient onboarding was easy, and patients demonstrated good adherence to the protocol (101% [82%-123%]). The usability of the PPG app was satisfactory with a high score in the System Usability Score questionnaire (80.0 [55.0-92.5]). Among 99 patients (mean age 66±9 years; 54% female), 8% had a prior AF diagnosis. Premature beats were common, with 96% of patients showing isolated premature beats (<6 in 960 PPG recordings) and 32% frequent premature beats (≥6 in 210 PPG recordings). The PPG algorithm suspected paroxysmal AF in 6 new cases. AF could be confirmed in 2 patients through resting 12-lead ECG and 1-lead handheld ECG device. One patient who was lost to follow-up. In the remaining 3 patients with suspected AF PPG recordings, analysis of 24-hour, 48-hour and 7-day Holter recordings revealed high burden premature (supra)ventricular beats. Two of these patients manifested self-terminating short episodes of supraventricular tachycardia. Conclusion 14-days opportunistic PPG app-based screening is feasible in COPD outpatient care and results in the detection of new AF cases and premature beats. This novel digital approach offers a practical method to implement recommended AF screening in COPD patients.

New-onset atrial fibrillation in patients with ST-elevation myocardial infarction

Abstract Background New-onset atrial fibrillation (NOAF) complicating ST-elevation myocardial infarction (STEMI) remains clinically challenging. Little is known regarding the long-term clinical impact of NOAF in the acute STEMI phase compared to a prior diagnosis of AF before the onset of STEMI. Methods We retrospectively reviewed consecutive patients undergoing percutaneous coronary intervention (PCI) for STEMI between May 2015 and September 2023. Patients were stratified based on NOAF diagnosis during the index-hospitalization vs. preexisting AF prior to the onset of STEMI. Long-term follow-up was obtained for stroke, major bleeding, or death. Results We analyzed 1327 consecutive patients undergoing PCI for STEMI. NOAF was detected in 117 patients (9%) and 69 patients (5%) had prior AF. Patients with NOAF and prior AF had similar baseline characteristics. NOAF patients were 65% males, with a mean age of 69 ± 13 years. All patients were treated with enoxaparin, but only 30% of patients with NOAF and 65% with prior AF were discharged with triple therapy, p<0.05. During a median follow-up of 696 days, the rates of stroke were 11% in patients with NOAF compared to 6% (p= 0.03) in patients with prior AF. Major bleeding occurred in 7% vs. 9%, p= 0.59, and death in 19% vs. 22%, p= 0.25 of patients with NOAF vs. prior AF. Conclusion NOAF was detected in almost 1 out of 10 STEMI patients and was associated with a similar rate of major bleeding and death as in patients with prior AF. The risk of NOAF for stroke might be higher than that of prior AF. These finding warrant confirmation in larger data sets.Central illustration

Clinical significance and prognostic value of right bundle branch block in permanent pacemaker patients

Abstract Aim In patients undergoing pacemaker implantation with no prior history of heart failure (HF), the presence of left bundle branch block (LBBB) has been identified as an independent predictor of HF-related death or hospitalization, while the prognostic significance of right bundle branch block (RBBB) remains uncertain. We aimed to assess the long-term risk of all-cause mortality in patients with a standard indication for permanent pacing and normal or moderately depressed left ventricular function when RBBB is detected at the time of implantation. Methods We retrospectively enrolled 1348 consecutive patients who had undergone single- or dual-chamber pacemaker implantation at the study center, from January 1990 to December 2022. Patients with a left ventricular ejection fraction ≤35% or a prior diagnosis of HF were excluded. Results The baseline 12-lead electrocardiogram revealed an RBBB in 241 (18%) and an LBBB in 98 (7%) patients. During a median follow-up of 65 [25th-75th percentile: 32-117] months, 704 (52%) patients died. The combined endpoint of cardiovascular death or HF hospitalization was reached by 173 (13%) patients. On multivariate analysis, RBBB was confirmed as independent predictor of death (Hazard Ratio, 1.33; 95% CI, 1.09–1.63; P=0.005). However, when considering the combined endpoint of cardiovascular death and HF hospitalization, this endpoint was independently associated with LBBB (Hazard Ratio, 2.13; 95% CI, 1.38–3.29; P<0.001), but not with RBBB. Conclusions In patients with standard pacemaker indications and normal or moderately depressed LV function the presence of basal RBBB was an independent predictor of mortality. However, it was not associated with the combined endpoint of cardiovascular death and HF hospitalization.Time to event

Effects of long-term continuous screening for atrial fibrillation on heart failure events - results from the randomized LOOP Study

Abstract Background Previous research established a solid link between atrial fibrillation (AF) and heart failure (HF). However, while two landmark trials have assessed AF screening for stroke prevention, the potential impact of AF screening on HF remains unclear. Purpose This secondary analysis of the LOOP Study aimed to investigate the effects of AF screening on HF events. Methods The LOOP Study was a randomized clinical trial evaluating long-term continuous AF screening with implantable loop recorder (ILR) in individuals aged 70-90 years and with ≥1 of arterial hypertension, diabetes mellitus, HF, and/or prior stroke. At inclusion, study participants were randomized 1:3 to either ILR screening or usual care. Anticoagulation was recommended upon AF detection, whereas other treatment was left to the discretion of the treating physician. In this secondary analysis, a cause-specific Cox regression model was applied to explore the effects of AF screening vs usual care on 1) time-to-first HF event and 2) total HF events, with the latter performed using the Andersen-and-Gill extension. HF event was defined as newly diagnosed HF with left ventricular ejection fraction ≤40% or any HF hospitalization in participants with prior diagnosis of HF with reduced ejection fraction. Results In total, 6004 participants were enrolled in the LOOP Study: 1501 in the ILR group vs 4503 in the Control group. The study population had a mean age of 75 years and slightly more males than females (53% vs 47%), whereas 266 (4.4%) were previously diagnosed with HF at baseline. During a median follow-up of 5.4 years, a total of 208 HF events were reported in 175 (2.9%) participants: 37 events among 34 (2.3%) participants in the ILR group vs 171 events among 141 (3.1%) participants in the Control group. For time-to-first HF event, the annualized event rate was 0.44%/year [95% confidence interval (CI): 0.30-0.62] vs 0.61%/year [95% CI: 0.51-0.72] for ILR vs Control, corresponding to a hazard ratio (HR) of 0.72 [95% CI: 0.50-1.05]. When assessing total HF events, a significantly lower event rate was observed in the ILR group (0.47%/year [95% CI: 0.33-0.65]) compared with the Control group (0.73%/year [95% CI: 0.62-0.84]), resulting in a HR of 0.65 [95% CI: 0.44-0.97]. Conclusions Among elderly individuals with additional stroke risk factors, long-term continuous AF screening led to a significantly reduced risk of total HF events, compared with usual care. This should be considered as hypothesis-generating and warrants further investigation.Cumulative incidence of HF event

#2022 Clinical outcomes in US patients initiating finerenone – a report from the FOUNTAIN platform

Abstract Background and Aims Evidence from clinical trials demonstrates that finerenone reduces the risk of cardiovascular and renal complications among patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). What is lacking is the evidence on finerenone use in real-world clinical practice. Method The present analysis is based on a longitudinal single-arm cohort study of patients initiating finerenone between July 2021 and August of 2023 and with prior diagnoses of CKD and T2D. Data were obtained from US electronic health records and insurance claims (OM1 Real-World Data CloudTM). CKD was defined as either having 1 diagnostic code for CKD stage 2-4 or unspecified stage, two estimated glomerular filtration rate (eGFR) measurements between 15 and 60 ml/min/1.73 m2, or two urine albumin to creatinine ratio (UACR) measurements over 30 mg/g; T2D was defined as having a diagnostic code for T2D. We described patient demographics, comorbidities, and comedications at baseline (365 days prior and including index date), and incidence rates of cardiovascular and renal outcomes, including eGFR and UACR changes over time. The presented analysis (NCT05703880) is part of the multi-national, multi-database observational research platform FOUNTAIN. Results We identified 28,056 new users of finerenone with prior CKD and T2D. The users had a mean (SD) age of 68.8 (10.8) years and 44.8% were female. Comorbidities of interest at baseline were hypertension (89.8%), cardiovascular disease (21.2%), neuropathy (13.4%), retinopathy (8.1%), heart failure (7.9%), and cerebrovascular disease (4.2%). Assessment of comedication use at baseline indicates that patients who initiate finerenone had exposure to renin–angiotensin system inhibitors (52.5%), sodium-glucose cotransporter-2 inhibitors (39.2%), or glucagon-like peptide-1 receptor agonists (27.4%) within 180 days prior to initiating finerenone. Overall, 82.5% of patients initiated finerenone at 10 mg/d, while 17.5% of patients started with 20 mg/d. Complete results including incidence rates of cardiovascular and renal outcomes, hyperkalemia events, and changes in kidney function measures (eGFR, UACR) during follow-up will be presented as part of the conference presentation. Conclusion Data from patients receiving finerenone as part of clinical practice in the USA suggest that finerenone is used concurrently with other renal and cardiovascular protective medication-classes recommended for patients with CKD and T2D.

Prescribing semaglutide for weight loss in non-diabetic, obese patients is associated with an increased risk of erectile dysfunction: a TriNetX database study.

Semaglutide was approved in June 2021 for weight loss in non-diabetic, obese patients. While package inserts include sexual dysfunction as a side effect, no study has assessed the degree of this risk. The objective of our study is to assess the risk of developing erectile dysfunction after semaglutide is prescribed for weight loss in obese, non-diabetic men. The TriNetX Research database was used to identify men without a diagnosis of diabetes ages 18 to 50 with BMI > 30 who were prescribed semaglutide after June 1st, 2021. Men were excluded if they had a prior erectile dysfunction diagnosis, any phosphodiesterase-5 inhibitors prescription, intracavernosal injections, penile prosthesis placement, history of testosterone deficiency, testosterone prescription, pelvic radiation, radical prostatectomy, pulmonary hypertension, or were deceased. We further restricted our cohort to non-diabetic, obese men by excluding men with a prior diabetes mellitus diagnosis, a hemoglobin A1c > 6.5%, or having ever received insulin or metformin. Men were then stratified into cohorts of those that did and did not receive a semaglutide prescription. The primary outcome was the risk of new ED diagnosis and/or new prescription of phosphodiesterase type 5 inhibitors at least one month after prescription of semaglutide. The secondary outcome was risk of testosterone deficiency diagnosis. Risk was reported using risk ratios with 95% confidence intervals (95% CI). 3,094 non-diabetic, obese men ages 18-50 who received a prescription of semaglutide were identified and subsequently matched to an equal number cohort of non-diabetic, obese men who never received a prescription of semaglutide. After matching, average age at index prescription for non-diabetic, obese men was 37.8 ± 7.8 and average BMI at index prescription was 38.6 ± 5.6. Non-diabetic men prescribed semaglutide were significantly more likely to develop erectile dysfunction and/or were prescribed phosphodiesterase type 5 inhibitors (1.47% vs 0.32%; RR: 4.5; 95% CI [2.3, 9.0]) and testosterone deficiency (1.53% vs 0.80%; RR: 1.9; 95% CI [1.2, 3.1]) when compared to the control cohort of non-diabetic men who never received a semaglutide prescription.

An Evaluation of Autologous Fat Injection as a Treatment for Velopharyngeal Insufficiency: A Review and Integrated Data Analysis.

Velopharyngeal insufficiency (VPI) is a condition characterized by incomplete separation of the oral and nasal cavities during speech production, thereby leading to speech abnormalities and audible nasal emissions. Subsequently, this adversely impacts communication and potentially interpersonal social interactions. Autologous fat grafting (AFG) to the velopharynx, a minimally invasive technique, aims to improve oronasal separation by providing bulk and advancing the posterior pharyngeal wall toward the soft palate. Despite its potential, the relative novelty of AFG in treating VPI has resulted in reporting of inconsistent indications, varied surgical techniques, and mixed outcomes across existing literature. This systemic review examined the evidence of AFG for VPI treatment over the past decade (2013-2023). A thorough search across five electronic databases yielded 233 studies, with 20 meeting the inclusion criteria (e.g., utilized fat injection as their selected VPI treatment, conducted study in human subjects, did not perform additional surgical procedure at time of fat injection). Selected studies encompassed patient and surgical intervention characteristics, perceptual speech assessment (PSA) scores, gap sizes, nasalance measurements, and complications. The majority of patients had a prior cleft palate diagnosis (78.2%), in which nasoendoscopy was the prevalent method for visualizing the velopharyngeal port defect. Fat harvesting predominantly occurred from the abdomen (64.3%), with an average injection volume of 6.3 mL across studies. PSA and subjective gap size scores were consistently higher preoperatively than postoperatively. PSA score analysis from seven studies revealed significant and sustained improvements postoperatively. Gap size score analysis from four studies demonstrated similar preoperative and postoperative differences. Complications were reported in 17 studies, yielding a 2.7% summative complication rate among 594 cases. Autologous fat grafting has emerged as a minimally invasive, safe, and effective treatment for mild to moderate VPI. However, challenges remain because of variability in patient selection criteria, diagnostic modalities, and outcome measurements. This review underscores the need for randomized control trials to directly compare AFG with standard-of-care surgical interventions, providing more conclusive evidence of its clinical efficacy.

Single-Center Experience of Patients with Plasma Cell Leukemia in the Era of New Therapeutics

Introduction: Plasma cell leukemia (PCL) can occur de novo as primary PCL (pPCL), or in patients with prior diagnosis of multiple myeloma (MM) as secondary PCL (sPCL). In 2021, the diagnostic criteria have been revised, establishing a new cut-off of ≥5% plasma cells in the peripheral blood. Lacking specific clinical trials, PCL is treated similarly to MM; however, outcome for patients with PCL remains poor. Here, we report outcomes for patients with pPCL and sPCL in the era of novel agents. Methods: We performed a retrospective analysis and identified 19 patients (11 pPCL, 8 sPCL) who have been treated for PCL between 2010 and 2022 at University Hospital Essen. Results: Patients with pPCL had a median overall survival (OS) of 37.8 months (95% CI: [15.4; 52.3] months) from diagnosis, with a median time to next treatment (TTNT) of 18.4 (2.0; 22.9) months. All patients were treated with a proteasome-inhibitor (PI)-based induction therapy, and the majority was consolidated with an autologous stem cell transplantation (SCT). Five of these patients received a tandem transplantation. Patients with sPCL had a median OS of only 1.5 months after diagnosis of PCL. Only 1 patient achieved a remission with daratumumab and subsequent allogenic SCT. Conclusion: With our study, we add evidence for a PI-based induction therapy followed by a consolidating autologous SCT for patients with pPCL and give further evidence that a tandem transplant concept might be beneficial. The diagnosis of sPCL remains devastating and needs new therapeutic approaches.

Association Between Autoimmune Diseases and Monoclonal Gammopathy of Undetermined Significance : An Analysis From a Population-Based Screening Study.

Monoclonal gammopathy of undetermined significance (MGUS) is a precursor of multiple myeloma (MM) and related conditions. In previous registry-based, retrospective studies, autoimmune diseases have been associated with MGUS. However, these studies were not based on a screened population and are therefore prone to ascertainment bias. To examine whether MGUS is associated with autoimmune diseases. A cross-sectional study within iStopMM (Iceland Screens, Treats, or Prevents MM), a prospective, population-based screening study of MGUS. Icelandic population of adults aged 40 years or older. 75 422 persons screened for MGUS. Poisson regression for prevalence ratios (PRs) of MGUS among persons with or without an autoimmune disease, adjusted for age and sex. A total of 10 818 participants had an autoimmune disorder, of whom 599 had MGUS (61 with a prior clinical diagnosis and 538 diagnosed at study screening or evaluation). A diagnosis of an autoimmune disease was not associated with MGUS (PR, 1.05 [95% CI, 0.97 to 1.15]). However, autoimmune disease diagnoses were associated with a prior clinical diagnosis of MGUS (PR, 2.11 [CI, 1.64 to 2.70]). Registry data were used to gather information on autoimmune diseases, and the homogeneity of the Icelandic population may limit the generalizability of these results. The study did not find an association between autoimmune disease and MGUS in a systematically screened population. Previous studies not done in systematically screened populations have likely been subject to ascertainment bias. The findings indicate that recommendations to routinely screen patients with autoimmune disease for MGUS may not be warranted. The International Myeloma Foundation and the European Research Council.

The Natural History of Eosinophilic Gastrointestinal Diseases Is Influenced by Age of Onset and Location of Involvement.

It is unknown whether concomitant esophageal involvement or anatomic location of eosinophilic infiltration affects the natural history of eosinophilic gastrointestinal disease (EGID). A retrospective cohort study was performed using the University of North Carolina EGID Clinicopathologic Database. Patients were adults and children with a prior EGID diagnosis based on clinicopathologic features. Demographics, clinical characteristics, treatment information, and procedural data were extracted from medical records. Clinical course and flare history were characterized. Among 97 patients, 43% had EGID + esophageal involvement and 57% had EGID only. Patients with esophageal involvement had a longer diagnostic delay preceding diagnosis (36.6 vs 11.6 months, P = 0.001), more dysphagia (50% vs 18%; P = 0.001), required more chronic therapy (77% vs 52%, P = 0.016), and exhibited more progressive disease (25% vs 6%, P = 0.027). A continuous disease course was most common in eosinophilic gastritis (78%) while patients with eosinophilic gastritis + eosinophilic enteritis (29%) and eosinophilic enteritis + eosinophilic colitis (50%) had the highest proportion of progressive and relapsing disease, respectively ( P = 0.045). A continuous disease course occurred more frequently in children (71%, P = 0.03) and those with single organ involvement (65%), whereas adults had more relapsing (39%) or progressive disease (18%). EGIDs with and without esophageal involvement display many similarities, although patients with esophageal involvement more frequently had dysphagia, had progressive disease courses, and required more chronic therapy. Location of involvement and age of onset affected the natural history with higher proportions of relapsing or progressive disease seen in adults and patients with small bowel or multiorgan involvement while a continuous disease course was more common in children and patients with gastric-only involvement.

Serological Evidence of Mpox Virus Infection During Peak Mpox Transmission in New York City, July to August 2022.

The extent to which infections may have been undetected in an epicenter of the 2022 mpox outbreak is unknown. A serosurvey (July and August 2022) assessed the seroprevalence and correlates of mpox infection among a diverse sample of asymptomatic patients with no prior mpox diagnoses and no known histories of smallpox or mpox vaccination. We present seropositivity stratified by participant characteristics collected via survey. Two-thirds of 419 participants were cismen (281 of 419), of whom 59.1% (166 of 281) reported sex with men (MSM). The sample also included 109 ciswomen and 28 transgender/gender nonconforming/nonbinary individuals. Overall seroprevalence was 6.4% (95% confidence interval [CI], 4.1%-8.8%); 3.7% among ciswomen (95% CI, 1.0%-9.1%), 7.0% among cismen with only ciswomen partners (95% CI, 2.0%-11.9%), and 7.8% among MSM (95% CI, 3.7%-11.9%). There was little variation in seroprevalence by race/ethnicity, age group, HIV status, or number of recent sex partners. No participants who reported close contact with mpox cases were seropositive. Among participants without recent mpox-like symptoms, 6.3% were seropositive (95% CI, 3.6%-9.0%). Approximately 1 in 15 vaccine-naive people in our study had antibodies to mpox during the height of the NYC outbreak, indicating the presence of asymptomatic infections that could contribute to ongoing transmission.

Higher prevalence of kidney function impairment among older people living with HIV in Uganda.

People living with HIV (PLWH) are at risk of kidney function impairment due to HIV-related inflammation, antiretroviral therapy (ART), diabetes mellitus, and hypertension. Older persons may experience a higher burden of chronic kidney disease (CKD) as kidney function declines with increasing age. There is a paucity of data comparing the prevalence of kidney function impairment in older PLWH to that in HIV-uninfected people in sub-Saharan Africa. We conducted a cross-sectional study among people aged ≥ 60 years living with and without HIV in Kampala, Uganda who were matched 1:1 by community location. We collected data on sociodemographics, comorbidities, and HIV-related clinical characteristics. We defined kidney function impairment as an estimated glomerular filtration rate(eGFR) < 60mls/min/1.73m2 with or without proteinuria. We constructed multivariable logistic regression models to study associations between participant characteristics and kidney function impairment. We enrolled 278 people (median age 66 years); 50% were PLWH, and 51.8% were female. Overall, the prevalence of kidney function impairment was 23.0% (95% CI:18.4%-28.4%); 33.1% (95% CI: 25.7%-41.4%) versus 12.9% (95% CI: 8.3%-19.7%) among people living with and without HIV (p-value < 0.01). The prevalence of proteinuria among PLWH versus people without HIV was 43.9% (95% CI:35.8%-52.3%) versus 19.4% (95% CI:13.6%-26.9%) p-value < 0.01. Living with HIV (OR = 3.89(95% CI: 2.04-7.41), p-value < 0.01), older age (OR = 1.13, (95% CI:1.07-1.20), p-value < 0.01), female sex (OR = 1.95, (95% CI:1.06-3.62), p-value = 0.03) and a prior diagnosis of hypertension (OR = 2.19(95% CI:1.02-4.67), p-value = 0.04) were significantly associated with kidney function impairment. HIV infection is strongly associated with kidney function impairment among older PLWH. Prioritizing routine measurements of kidney function and proteinuria in older PLWH will enable early detection and institution of measures to reduce the progression of kidney disease.

Treatment of Periprosthetic Hip Fractures Vancouver B1 and C: The Significance of Bicortical Fixation. A Bicentric Study Comparing Two Osteosynthesis Systems.

INTRODUCTION The incidence of periprosthetic fractures (PFFs) is estimated to range from 0.1% to 4.1%1, due to the increasing prevalence of joint arthroplasties, coupled with an aging population. Numerous risk factors, including advanced age (>80 years), female gender, implant type, prior diagnoses of osteonecrosis and rheumatoid arthritis, revision surgery, aseptic stem mobilization, and the use of non-cemented stems, have been identified. Survivors of periprosthetic fractures often experience functional deterioration, facing a fourfold higher risk of hospitalization for postoperative complications compared to patients undergoing primary implantation, especially in the first postoperative year. MATERIALS AND METHODS Between 2018 and 2022, at the Maggiore Hospitals in Bologna and the San Matteo Policlinic in Pavia, we performed osteosynthesis on 84 patients with periprosthetic fractures of Vancouver type B1 or C. In 38 patients, we employed angular stable plates with the Zimmer Biomet NCB-PP® system. In 46 patients, we utilized INTRAUMA plates: DF distal femur and PFF proximal. Relevant postoperative follow-up outcomes considered included reintervention, infectious complications, radiographic healing, and functional recovery, with reference to changes in the Glasgow Outcome Scale (GOS) and the Harris Hip Score (HHS). All patients underwent clinical and radiographic evaluations during the follow-up period, averaging 28 months (range: 12-48 months), with a minimum follow-up duration of 12 months. RESULTS At the 4-month postoperative assessment, 71% of patients maintained their preoperative functional level, 19% experienced a 1-point GOS scale drop, and 10% died (GOS 5). The average HHS at 4 months was 80.2 points (range: 65-90). At the 6-month follow-up, 98.2% of patients achieved complete healing on radiographic examination. Only 1 patient (1.2%) developed a pseudoarthrosis site with synthesis device rupture. Only 1 patient (1.2%) required additional surgical treatment 2 years later due to the development of un aseptic perisynthetic fluid collection, while the remaining 5 patients (6%) who developed complications benefited from conservative treatment: 4 patients (3.6%) with infectious complications were treated with intravenous antibiotics. In the 2 patients (2.3%) with mobilization or rupture of synthesis devices, clinical and radiographic monitoring was opted for. 8 patients (10.7%) died: one 48 hours after the surgery, and the other 7 more than one month after the surgery. CONCLUSION Our clinical findings align with to existing scientific literature on periprosthetic fractures (B1 and C according to Vancouver classification). Moreover, good stability has been guaranteed at the radiological follow up by Zimmer Biomet NCB-PP® and INTRAUMA DF distal femur and PFF proximal plates. The locking construct allows for improved stability especially in osteoporotic bone.

The effect of fixation type on periprosthetic fractures in high-risk patients who have osteoporosis undergoing total joint arthroplasty

IntroductionMinimizing the burden of periprosthetic fractures (PFF) following total joint arthroplasty (TJA) with regard to morbidity and mortality remains an outcome of interest. Patient and surgical risk factors, including osteoporosis and fixation type, have not truly been optimized in patients undergoing TJA as a means to reduce the risk of PFF. As such, we examined: (1) What percentage of patients who underwent THA and total knee arthroplasty (TKA) met the criteria for osteoporosis screening? (2) How did the 5-year rate of PFF and fragility fracture differ in the high-risk and low-risk groups for osteoporosis between the cemented and cementless cohorts? (3) What percentage of the aforementioned patients received a dual x-ray absorptiometry (DEXA) scan before THA or TKA? MethodsWe queried an all-payer, national database from April 1, 2016 to December 31, 2021, to identify high-risk and low-risk patients who underwent TJA with a cementless or cemented fixation. High-risk patients met at least one of the following criteria: men at least 70 years old, women at least 65 years old, or patients at least 60 years old who have the following: tobacco use, alcohol abuse, body mass index <18.5, prior fragility fracture, chronic systemic corticosteroids, or genetic condition affecting sex hormones or bone mineral density. Exclusion criteria were a diagnosis of malignancy, high-energy events (motor vehicle collision), those who underwent TJA indicated for fracture, patients less than 50 years old, those who had a prior diagnosis of or treatment for osteoporosis, and a minimum follow-up of less than 2 years. ResultsThere were 384,783 patients (67.1 %) who underwent cementless TKA and 67,774 patients (11.8 %) who underwent cementless TKA who were considered high risk. Additionally, there were 62,505 patients (10.9 %) who underwent cemented THA and 58,667 patients (10.2 %) who underwent cementless THA and were considered high risk. The cementless cohort had a 5-year periprosthetic fracture risk following TKA of 7.8 % (95 % CI, 5.56 to 10.98) in comparison to 4.30 % in the cemented cohort (85 % CI, 3.98 to 4.65), P < 0.0001. The high-risk cementless cohort had a 5-year periprosthetic fracture risk following THA of 7.9 % (95 % confidence interval (CI), 6.87 to 9.19) in comparison to 7.78 % in the cemented cohort (85 % CI, 6.77 to 8.94), P < 0.0001. ConclusionThere is an increased risk of PFF at 5 years following TKA in patients at high risk for osteoporosis undergoing cementless fixation in comparison to cemented fixation. There is an increased risk of PFF at 5 years following THA in patients at high risk for osteoporosis for both cementless fixation and cemented fixation, but no clinically meaningful difference between the two groups. Addressing the shortcomings of the underutilization of bone density scans and better selecting appropriate patients for TJA based on bone quality and fracture risk can help expedite the process of improving the current state of practice.

The risk of skin cancer in women who carry BRCA1 or BRCA2 mutations

BackgroundIt has not been clearly established if skin cancer or melanoma are manifestations of BRCA1 or BRCA2 mutation carrier status. Estimating the risk of skin cancer is an important step towards developing screening recommendations.MethodsWe report the findings of a prospective cohort study of 6,207 women from North America who carry BRCA1 or BRCA2 mutations. Women were followed from the date of baseline questionnaire to the diagnosis of skin cancer, to age 80 years, death from any cause, or the date of last follow-up.ResultsDuring the mean follow-up period of eight years, 3.7% of women with a BRCA1 mutation (133 of 3,623) and 3.8% of women with a BRCA2 mutation (99 of 2,584) reported a diagnosis of skin cancer (including both keratinocyte carcinomas and melanoma). The cumulative risk of all types of skin cancer from age 20 to 80 years was 14.1% for BRCA1 carriers and 10.7% for BRCA2 carriers. The cumulative risk of melanoma was 2.5% for BRCA1 carriers and 2.3% for BRCA2 carriers, compared to 1.5% for women in the general population in the United States. The strongest risk factor for skin cancer was a prior diagnosis of skin cancer.ConclusionThe risk of non-melanoma skin cancer in women who carry a mutation in BRCA1 or BRCA2 is similar to that of non-carrier women. The risk of melanoma appears to be slightly elevated. We suggest that a referral to a dermatologist or primary care provider for BRCA mutation carriers for annual skin examination and counselling regarding limiting UV exposure, the use of sunscreen and recognizing the early signs of melanoma might be warranted, but further studies are necessary.

Development, validation and application of single molecule molecular inversion probe based novel integrated genetic screening method for 29 common lysosomal storage disorders in India

BackgroundCurrent clinical diagnosis pathway for lysosomal storage disorders (LSDs) involves sequential biochemical enzymatic tests followed by DNA sequencing, which is iterative, has low diagnostic yield and is costly due to overlapping clinical presentations. Here, we describe a novel low-cost and high-throughput sequencing assay using single-molecule molecular inversion probes (smMIPs) to screen for causative single nucleotide variants (SNVs) and copy number variants (CNVs) in genes associated with 29 common LSDs in India.Results903 smMIPs were designed to target exon and exon–intron boundaries of targeted genes (n = 23; 53.7 kb of the human genome) and were equimolarly pooled to create a sequencing library. After extensive validation in a cohort of 50 patients, we screened 300 patients with either biochemical diagnosis (n = 187) or clinical suspicion (n = 113) of LSDs. A diagnostic yield of 83.4% was observed in patients with prior biochemical diagnosis of LSD. Furthermore, diagnostic yield of 73.9% (n = 54/73) was observed in patients with high clinical suspicion of LSD in contrast with 2.4% (n = 1/40) in patients with low clinical suspicion of LSD. In addition to detecting SNVs, the assay could detect single and multi-exon copy number variants with high confidence. Critically, Niemann-Pick disease type C and neuronal ceroid lipofuscinosis-6 diseases for which biochemical testing is unavailable, could be diagnosed using our assay. Lastly, we observed a non-inferior performance of the assay in DNA extracted from dried blood spots in comparison with whole blood.ConclusionWe developed a flexible and scalable assay to reliably detect genetic causes of 29 common LSDs in India. The assay consolidates the detection of multiple variant types in multiple sample types while having improved diagnostic yield at same or lower cost compared to current clinical paradigm.

Residential exposure to air pollution and incidence of leukaemia in the industrial area of Viadana, Northern Italy

BackgroundExposure to air pollution has been proposed as one of the potential risk factors for leukaemia. Work-related formaldehyde exposure is suspected to cause leukaemia. MethodsWe conducted a nested register-based case-control study on leukaemia incidence in the Viadana district, an industrial area for particleboard production in Northern Italy. We recruited 115 cases and 496 controls, frequency-matched by age, between 1999 and 2014. We assigned estimated exposures to particulate matter (PM10, PM2.5), nitrogen dioxide (NO2), and formaldehyde at residential addresses, averaged over the susceptibility window 3rd to 10th year prior to the index date. We considered potential confounding by sex, age, nationality, socio-economic status, occupational exposures to benzene and formaldehyde, and prior cancer diagnoses. ResultsThere was no association of exposures to PM10, PM2.5, and NO2 with leukaemia incidence. However, an indication of increased risk emerged for formaldehyde, despite wide statistical uncertainty (OR 1.46, 95%CI 0.65–3.25 per IQR-difference of 1.2 μg/m3). Estimated associations for formaldehyde were higher for acute (OR 2.07, 95%CI 0.70–6.12) and myeloid subtypes (OR 1.79, 95%CI 0.64–5.01), and in the 4-km buffer around the industrial facilities (OR 2.78, 95%CI 0.48–16.13), although they remained uncertain. ConclusionsThis was the first study investigating the link between ambient formaldehyde exposure and leukaemia incidence in the general population. The evidence presented suggests an association, although it remains inconclusive, and a potential significance of emissions related to industrial activities in the district. Further research is warranted in larger populations incorporating data on other potential risk factors.

Prevalences and Interrelationships of Post COVID-19 Fatigue, Sleep Disturbances, and Depression in Healthy Young and Middle-Aged Adults.

Background: An evaluation of the persistence of symptoms following COVID-19 in economically active young and middle-aged adults is crucial due to its significant socioeconomic impact resulting from compromised work performance. Methods: A prospective, multicenter study at 12 South Korean hospitals from January to December 2022 involved telephone interviews along with validated questionnaires. Results: Among 696 participants with a median age of 32 and no prior diagnoses, 30% of participants experienced persistent fatigue, while 21.4% suffered from sleep disturbance at 6 months following infection. Additionally, approximately 25% of the participants exhibited depression that endured for up to 6 months. Symptomatic individuals at 3 months exhibited a significantly higher prevalence of persistent fatigue, sleep disturbances, and depression at 6 months compared to those who remained asymptomatic. Notably, sleep disturbance and persistent fatigue at 3 months emerged as significant independent predictors of the presence of depression at 6 months. Conclusions: Even among young and middle-aged healthy adults, prolonged fatigue, sleep disturbance, and depression exhibit a significant prevalence and persisted for up to 6 months. Therefore, implementing a workplace management protocol for these symptoms is essential to mitigate the socioeconomic burden caused by the impairment of work efficiency.

Dynamic risk stratification of worsening heart failure using a deep learning-enabled implanted ambulatory single-lead electrocardiogram.

Implantable loop recorders (ILRs) provide continuous single-lead ambulatory electrocardiogram (aECG) monitoring. Whether these aECGs could be used to identify worsening heart failure (HF) is unknown. We linked ILR aECG from Medtronic device database to the left ventricular ejection fraction (LVEF) measurements in Optum® de-identified electronic health record dataset. We trained an artificial intelligence (AI) algorithm [aECG-convolutional neural network (CNN)] on a dataset of 35 741 aECGs from 2247 patients to identify LVEF ≤ 40% and assessed its performance using the area under the receiver operating characteristic curve. Ambulatory electrocardiogram-CNN was then used to identify patients with increasing risk of HF hospitalization in a real-world cohort of 909 patients with prior HF diagnosis. This dataset provided 12 467 follow-up monthly evaluations, with 201 HF hospitalizations. For every month, time-series features from these predictions were used to categorize patients into high- and low-risk groups and predict HF hospitalization in the next month. The risk of HF hospitalization in the next 30 days was significantly higher in the cohort that aECG-CNN identified as high risk [hazard ratio (HR) 1.89; 95% confidence interval (CI) 1.28-2.79; P = 0.001] compared with low risk, even after adjusting patient demographics (HR 1.88; 95% CI 1.27-2.79 P = 0.002). An AI algorithm trained to detect LVEF ≤40% using ILR aECGs can also readily identify patients at increased risk of HF hospitalizations by monitoring changes in the probability of HF over 30 days.