Sequelae Of Disease Research Articles

Breathing-Based Meditation for Improving COPD Burden: A Mixed Single-Case and Qualitative Approach

Chronic obstructive pulmonary disease (COPD) impacts the physiological and psycho-emotional aspects of life. COPD-related secondary sequelae also synergistically interact with each other. For example, dyspnea affects the severity of breath, body functions, and the mind (e.g., anxiety, panic, fear). Such negative psycho-emotional states can further negatively impact the breath and the body (e.g., increased dyspnea). Given the breadth of the impact of COPD on multiple facets of health and well-being, it is essential to investigate comprehensive approaches to managing COPD, simultaneously addressing the mind, body, and breath. Sudarshan Kriya Yoga (SKY), a breathwork meditation program, has previously yielded a wide range of physiological and psycho-emotional benefits but has not been explored in individuals with COPD. Using single-case multiple-baseline and qualitative phenomenology methodologies, this study investigated 1) the relation between dyspnea and SKY and 2) the feasibility and general perceived effectiveness of SKY among individuals with COPD. Nine individuals with varying severities of COPD participated. Data collection included ratings of perceived dyspnea (work of breathing, shortness of breath, dyspnea-related distress, dyspnea-related anxiety) and semi-structured in-depth interviews. Results suggest that SKY is feasible and acceptable for individuals with COPD. Additionally, the results demonstrate proof of concept that SKY can help alleviate aspects of the COPD disease burden related to the mind, body, and breath as well as reduce the cyclical effect of the disease sequelae. Larger-scale trials are warranted, but this study is the first to support SKY as a viable complementary and integrative health approach for individuals with COPD.

The Delta III and Delta Xtend reverse shoulder arthroplasty—risk of revision and failure mechanisms: a report on 3650 cases from the Norwegian Arthroplasty Register 1994-2021

The Delta reverse shoulder arthroplasty (RSA) is commonly used worldwide and is the most frequently used RSA in Norway. The aim of this registry-based study was to report 10- and 20-year implant survival, risk of revision, and reasons for revision in 2 consecutive time periods for Delta III (1994-2010) and Delta Xtend (2007-2021) prostheses. We included 3650 primary RSAs reported to the Norwegian Arthroplasty Register: 315 Delta III (42% cemented stems) and 3335 Delta Xtend (88% cemented stems). We used Kaplan-Meier analyses to investigate implant survival. The reasons for revision were compared for the 2 designs and fixation technique. Factors that could influence the risk of revision, such as implant design, fixation technique, and patient factors, were investigated using Cox regression analyses with adjustments for age, sex, and diagnosis. Patients operated with Delta III were more likely to be diagnosed with inflammatory disease or fracture sequela, whereas acute fracture, osteoarthritis, and cuff arthropathy were the most frequent indications for Delta Xtend. Ten-year survival was 93.0% (95% confidence interval [CI]: 87.0-99.0) (cemented stem) and 81.6% (95% CI: 75.3-87.9) (uncemented stem) for Delta III and 94.7% (95% CI: 93.3-96.1) (cemented stem) and 95.7% (95% CI: 88.3-100) (uncemented stem) for Delta Xtend. Twenty-year survival for Delta III (uncemented stem) was 68.2% (95% CI: 58.8-77.6). Compared with DeltaXtend (cemented stem) at 10-year follow-up, we found a higher risk of revision for Delta III (uncemented stem) (hazard ratio [HR]: 2.9, 95% CI: 1.7-5.0), whereas no significant difference was found for Delta III (cemented stem) and Delta Xtend (uncemented stem). The most common reason for revision of Delta III (uncemented stem) was glenoid loosening followed by deep infection and instability. Instability was the most frequent revision cause for Delta Xtend (both cemented and uncemented stem). Men had an overall higher revision risk than women (HR: 2.8 [95% CI: 2.0-3.9]), and patients with fracture sequela had increased risk for revision (HR: 2.8, 95% CI: 1.7-4.7) compared with patients with osteoarthritis. We found that Delta III (uncemented stem) had a higher risk of revision compared with Delta Xtend (cemented stem). The risk of revision for glenoid component loosening was lower for Delta Xtend, but revisions due to instability/dislocation are still a concern. This register study cannot determine whether the differences found were caused by differences in implant design or other factors that changed during the study period. Risk of revision may have been affected by the indication for primary operation.

Typical hemophagocytic syndrome associated with cytomegalovirus infection in an immunocompetent patient: a case report and literature review.

Cytomegalovirus (CMV) infection is currently prevalent in populations throughout the world, and 56%‍-94% of the global population is seropositive for CMV. CMV infection mainly affects immunocompromised hosts. In these cases, it can cause significant symptoms, tissue-invasive disease, and many sequelae including death (Dioverti and Razonable, 2016). The vast majority of healthy adults with CMV infection experience an asymptomatic course; when symptomatic, it manifests as a mononucleosis-like syndrome in approximately 10% of patients (Sridhar et al., 2018). The gastrointestinal tract and central nervous system appear to be the most frequent sites of severe CMV infection in immunocompetent individuals (Rafailidis et al., 2008). However, CMV infection is relatively rarely recorded in immunocompetent hosts.

Association between inflammatory bowel disease and subsequent depression or anxiety disorders - A retrospective cohort study of 31,728 outpatients

BackgroundCrohn's disease (CD) and ulcerative colitis (UC) are characterized by chronic intestinal and systemic inflammation. The extraintestinal sequelae of inflammatory bowel disease (IBD) are major contributors to disease morbidity and significantly affect patients' quality of life. Here, we evaluated the association between IBD and subsequent depression or anxiety disorder in a large outpatient collective from Germany. Methods15,864 individual IBD patients (CD: n = 6,791, UC: n = 9073) and 15,864 nearest neighbor propensity score matched patients without IBD were included from the Disease Analyzer database (IQVIA). Diagnoses of depression and anxiety disorders were compared between IBD and non-IBD patients during a five-year follow-up period using Kaplan-Meier estimators and Cox-regression models. ResultsAfter 5 years of follow-up, depression was diagnosed in 14.4% of CD patients versus 10.2% of matched pairs (p < 0.001) and in 13.1% of UC patients versus 10.1% of matched pairs (p < 0.001). In line, the incidence of anxiety order was significantly higher among CD (4.7% vs. 4.4%, p = 0.009) and UC patients (4.3% vs. 3.5%, p = 0.005). Regression analysis confirmed a significant association between IBD and both mental conditions (Hazard Ratio (HR)CD/depression: 1.40, HRUC/depression: 1.32, HRCD/anxiety disorder: 1.21, HRUC/anxiety disorder: 1.28). Subgroup analyses revealed a stronger association for CD and depression (HR: 1.51) and UC and depression (HR:1.49) among male patients as well as UC and anxiety disorders (HR: 1.51) among female patients. ConclusionOur data argue for a significant association between IBD and mental diseases including depression and anxiety disorders. Although further pathophysiological research is warranted, we hypothesize that specific psychological screening measures in IBD patients could improve quality of life and outcome.

Association between sequelae of COVID-19 with periodontal disease and obesity: A cross-sectional study.

To assess the sequelae of coronavirus disease 2019 (COVID-19) and associated factors, such as obesity and periodontitis in adults. The study included 128 individuals aged ≥35 years with a history of a diagnosis of COVID-19 through real-time polymerase chain reaction (RT-PCR), from Pelotas, Brazil. Self-report sequelae from COVID-19 were defined as the primary outcome. A questionnaire containing sociodemographic, medical, behavioral and self-report of sequelae of COVID-19 was applied. A complete periodontal clinical examination was performed. Weight and height were assessed. Uni-, bi- and multivariate analyses were performed using Poisson regression with robust variance. Additional analyses were performed considering obesity as a subgroup. When considering the whole sample, no statistically significant associations between sequelae of COVID-19 with periodontitis (prevalence ratio [PR]:1.14;95% confidence interval [95%CI]: 0.80-1.61) and obesity (0.93 [0.68-1.26]) were identified. In the subgroup analysis, considering only individuals with obesity, those diagnosed with generalized periodontitis had 86% higher probability to have sequelae of COVID-19 when compared to individuals with periodontal health or localized periodontitis. However, when only those without obesity were considered, no significant association with periodontal status was detected (0.82 [0.55-1.23). No significant association with periodontal status were observed when the severity of sequelae (no sequelae, 1 sequela, and >1 sequela) were considered (p>0.05). Individuals diagnosed with obesity and periodontitis have a higher PR of reporting sequelae from COVID-19 compared to individuals with only obesity.

Intrauterine enzyme replacement therapies for lysosomal storage disorders: Current developments and promising future prospects.

Lysosomal storage disorders (LSDs) are a group of monogenic condition, with many characterized by an enzyme deficiency leading to the accumulation of an undegraded substrate within the lysosomes. For those LSDs, postnatal enzyme replacement therapy (ERT) represents the standard of care, but this treatment has limitations when administered only postnatally because, at that point, prenatal disease sequelae may be irreversible. Furthermore, most forms of ERT, specifically those administered systemically, are currently unable to access certain tissues, such as the central nervous system (CNS), and furthermore, may initiate an immune response. In utero enzyme replacement therapy (IUERT) is a novel approach to address these challenges evaluated in a first-in-human clinical trial for IUERT in LSDs (NCT04532047). IUERT has numerous advantages: in-utero intervention mayprevent early pathology; the CNS can be accessed before the blood-brain barrier forms; and the unique fetal immune system enables exposure to new proteins with the potential to prevent an immune response and may induce sustained tolerance. However, there are challenges and limitations for any fetal procedure that involves two patients. This article reviews the current state of IUERT for LSDs, including its advantages, limitations, and potential future directions for definitive therapies.

Lamivudine and Entecavir for Acute Hepatitis B: A Systematic Review and Meta-Analysis.

Acute hepatitis B infection is associated with severe liver disease and chronic sequelae in some cases. The purpose of this review was to determine the efficacy of nucleoside analogues (NA) (lamivudine versus entecavir) compared to placebo or no intervention for treating acute primary HBV infection. A meta-analysis for drug intervention was performed, following a fixed-effect model. Randomized controlled trials (RCTs) and quasi-randomized studies that evaluated the outcomes of NA in acute hepatitis B infection were included. The following outcomes were considered: virological cure (PCR negative), elimination of acute infection (seroconversion of HBsAg), mortality, and serious adverse events. Five trials with 627 adult participants with severe acute hepatitis B defined by biochemical and serologic parameters were included. Virological cure did not favor any intervention: OR 0.96, 95% CI 0.54 to 1.7 (p = 0.90), I2 = 58%. Seroconversion of HBsAg to negative favored placebo/standard-of-care compared to lamivudine: OR 0.54, 95% CI 0.33 to 0.9 (p = 0.02), I2 = 31%. The only trial that compared entecavir and lamivudine favored entecavir over lamivudine (OR: 3.64, 95% CI 1.31-10.13; 90 participants). Adverse events were mild. There is insufficient evidence that NA obtain superior efficacy compared with placebo/standard-of-care in patients with acute viral hepatitis, based on low quality evidence.

Post-acute sequelae of COVID-19 in solid organ transplant recipients.

Post-acute sequelae of coronavirus disease 2019 (COVID-19) (PASC), defined as prolonged symptoms following an episode of COVID-19, is not well-characterized in solid organ transplant recipients (SOTR). In this study, we aimed to assess the prevalence of PASC in SOTR, its descriptive characteristics, and associated risk factors. We retrospectively identified SOTRs with acute COVID-19 between June 1, 2020 and April 15, 2022, and abstracted demographic and medical history, characteristics of acute COVID-19 illness, and COVID-19 vaccination status. We defined PASC as ongoing/new symptoms present at 6weeks or longer following acute COVID-19 diagnosis. Among 208 SOTRs with acute COVID-19, 72 (35%) developed PASC. Common symptoms were respiratory symptoms (67%), headache (40%), and difficulty concentrating (10%). Severe acute COVID-19 disease and presence of respiratory symptoms were associated with higher odds of PASC in multivariable analyses, while receipt of at least one COVID-19 vaccination prior to transplantation was protective. We found that PASC occurs in about a third of SOTRs with acute COVID-19 and has similar symptoms as described previously in immunocompetent hosts. Pre-transplant vaccination may be protective. Further prospective multicenter studies are needed.

Оценка реабилитации детей-реконвалесцентов после инфекционных заболеваний

The fact that the disease sequelae can limit the development of the growing child’s activity is the feature of pediatric medical rehabilitation, that is why there is a need for repeated courses of rehabilitation or habilitation, where each subsequent course is a continuation of the previous one. The specialist’s mission is to determine indications for rehabilitation. The paper reports phenomenology and methods to diagnose abnormal activity and participation in convalescent children after infectious diseases in order to set the rehabilitation goals in the International Classification of Functioning, Disability and Health domains (categories). The use of method to estimate activity and participation from the point of view of both child and parent or caregiver is considered. The paper provides information useful for specialists dealing with the issues of rehabilitation of children after infectious diseases.

Patient-Reported Outcomes (PROs) 3 and 6 Months After Pulmonary Rehabilitation Following COVID-19

If COVID-19 disease sequelae also (co-)affect the respiratory organs, national and international guidelines recommend pulmonary rehabilitation (PR). So far, however, no studies are available from Germany on the course after PR, nor on possible course differences between the two Long COVID subgroups "Ongoing symptomatic COVID-19" and "Post-COVID-19 syndrome" (PCS). In a prospective observational study, patient-reported outcomes (PROs) regarding exertional dyspnea, quality of life, pain, fatigue, depression, and anxiety were assessed at the beginning of PR (T1), end of PR (T2), and after 3 (T3) and 6 months (T4). Statistical analyses were performed using latent difference models. There were 224 rehabilitation patients (MAge=54.4; SDAge=10.4; 42.0% female) included in the study. During PR, all PROs improved significantly. After PR, improvements either persisted with large pre-post effect sizes (exertional dyspnea, quality of life), decreased slightly to small pre-post effect sizes (depression, fatigue), or decreased to baseline levels (anxiety, pain). PCS patients had greater burdens in depression, fatigue, and pain at baseline, but did not differ in trajectories. Indicators of the severity of the preceding acute phase (oxygen therapy, ICU treatment, ventilation) were associated with higher burdens at T0 in depression, fatigue, and pain, but not with the courses during and after PR. In contrast, female patients showed higher burdens in both depression and fatigue at T1 and higher pre-post effects than male patients. The fact that improvements in PROs occurred in both subgroups only during PR, but not during the follow-up period suggests that the changes are not due to the natural healing process but at least partly due to PR. Moreover, the results suggest that both patient groups may benefit from PR. Persisting improvements in exertional dyspnea and quality of life and, to a reduced extent, in depression and fatigue until 6 months after PR, but not in pain and anxiety warrant study of additional multimodal interventions that may be needed to maintain these effects.

MTHFR mutation: Another unifying etiology of chronic overlapping pain conditions

Introduction and Objective:Chronic pelvic pain (CPP) is a heterogeneous condition with multiple etiologies. Better characterization and understanding of CPP will lead to new therapeutic options and individualization of care, especially in patients with chronic overlapping pain syndromes (COPCs), which increase complexity of diagnosis. In this study, we present 6 patients with COPC and complex CPP, non-focal exam, who tested negative for small fiber neuropathy but who reported a history of methylenetetrahydrofolate reductase (MTHFR) mutations, and retrospective review of 76 patients with MTHFR mutation. This study explores through literature review whether MTHFR mutations play a role in the pathogenesis of chronic pelvic pain and overlapping pain conditions in a subset of patients with COPCs. Methods:Study design included an observational study of 6 patients, a retrospective cross-sectional study of 76 patients, and a literature review. Patients at our institution who tested positive for MTHFR mutations were included in the study; most had been seen in the cardiology/hematology clinics due to the association of MTHFR with clotting disorders. Chart review was performed to identify the presence of pain syndromes and specifically CPP. A review of the literature was undertaken to form a hypothesis for mechanisms that could explain the association between MTHFR mutations and chronic overlapping pain syndromes. Results:Of 76 patients with MTHFR mutations seen primarily in non-pain focused cardiology visits, 30 (39%) had some form of pain syndrome documented, 11 of whom (14%) specifically had CPP. The review below suggests that MTHFR plays a role in the maintenance of nerve tissue and conductance, neural tube defects, and paresthesia. Literature review revealed that MTHFR mutations have been linked with chronic pain and pathological processes such as chronic migraine, interstitial cystitis/bladder pain syndrome, sequelae of chronic Lyme disease, and fibromyalgia. Conclusions:The etiology of chronic pelvic pain is complex. Multisystem pain extending beyond the pelvis complicates the differential diagnosis but suggests a systemic cause. MTHFR mutations may play a unifying role in a subset of chronic pelvic pain patients with concomitant chronic overlapping pain syndromes. The mutations may affect folate metabolism pathways in these patients and hinder the ability to maintain nerve fibers over time, leading to dereliction of pain signal conduction. Disturbance of these pathways may have a role in chronic overlapping pain syndromes and complex pelvic pain.

The role of the multidisciplinary team in surgical management of intractable tubo-ovarian abscess as a late sequelae of challenging Crohn's disease in the modern era: A case report and review of current literature.

Chronic, severe Crohn's disease in a young female patient can result in surgical complexity. The rarity of the presentation of intractable pelvic abscesses within this etiology with additional considerations given to fertility concerns and hence requirement for input from a multi-disciplinary team makes this a vital case in building a consensus for evidence-based surgical management. A 29-year-old nulliparous woman was referred to our tertiary centre for surgical management of Crohn's disease with known tubo-ovarian abscess and abdominoperineal and abdominal wall sinuses. Her previous surgical history included 4 midline laparotomies, subtotal colectomy and proctectomy with stoma formation. The patient underwent egg collection to preserve fertility. This was followed by midline laparotomy and abdominoperineal resection, which involved a retrograde radical modified hysterectomy using the Hudson technique, alongside excision of the perineal sinus, with reconstruction of the perineal defect using an internal pudendal artery perforator gluteal fold flap, and in addition to excision and drainage of the abdominal wall abscess. Involvement was sought from gynecological oncology, colorectal, urology, plastics, stoma, fertility, microbiology, and gastroenterology teams, which enabled successful preservation of end organ function and improvement in patient psychological well-being. This case is a paradigm of surgical challenge, requiring expert gynecological oncology techniques including a retroperitoneal approach, nerve and vessel sparing considerations alongside colorectal and urological procedures. Moreover, we believe that our blueprint for effective multi-disciplinary practice will inform the future management of gynecological surgery. Therefore this report aims to contribute towards the optimum management of the gynecological sequelae of Crohn's disease.

Localized cardiac small molecule trajectories and persistent chemical sequelae in experimental Chagas disease

Post-infectious conditions present major health burdens but remain poorly understood. In Chagas disease (CD), caused by Trypanosoma cruzi parasites, antiparasitic agents that successfully clear T. cruzi do not always improve clinical outcomes. In this study, we reveal differential small molecule trajectories between cardiac regions during chronic T. cruzi infection, matching with characteristic CD apical aneurysm sites. Incomplete, region-specific, cardiac small molecule restoration is observed in animals treated with the antiparasitic benznidazole. In contrast, superior restoration of the cardiac small molecule profile is observed for a combination treatment of reduced-dose benznidazole plus an immunotherapy, even with less parasite burden reduction. Overall, these results reveal molecular mechanisms of CD treatment based on simultaneous effects on the pathogen and on host small molecule responses, and expand our understanding of clinical treatment failure in CD. This link between infection and subsequent persistent small molecule perturbation broadens our understanding of infectious disease sequelae.

Better COVID-19 Outcomes in Children with Good Asthma Control

Factors associated with COVID-19 presentation in children with asthma are poorly defined. Our study aimed to assess the clinical course of COVID-19 in children with asthma, with particular attention to possible risk factors for severe disease and long-term sequelae in this group of patients. We assessed the occurrence of SARS-CoV-2 infection in children with asthma six months before their regular outpatient visit to the asthma clinic. Characteristics of patients presenting with signs of SARS-CoV-2 upper (URTI) or lower respiratory tract infection (LRTI) were compared. We focused on factors previously associated with COVID-19 severity. Twenty-seven percent of patients (57/210) reported exposure to SARS-CoV-2 infection. In the symptomatic group, 36% (15/42) reported symptoms of LRTI and 64% (27/42) of URTI. Poorer asthma control was observed in patients with LRTI compared to URTI (80% vs. 7%, p &lt; 0.001). In addition, children with poorer asthma control had a higher risk of presenting with SARS-CoV-2 LRTI in a multiple logistic regression analysis. COVID-19 disease course was not associated with regular ICS use and asthma severity. However, patients on regular ICS had better asthma control (p = 0.026). We found no PFT deterioration post-COVID-19 in either group of patients. Our results suggest good asthma control and treatment adherence prior to infection are associated with better COVID-19 outcomes in children with asthma.

Direct Immunofluorescence Findings and Factors Affecting Conjunctival Biopsy Positivity in Ocular Mucous Membrane Pemphigoid.

The aim of this study was to describe the direct immunofluorescence (DIF) findings and factors affecting conjunctival biopsy positivity in patients clinically diagnosed with ocular mucous membrane pemphigoid (OMMP). This retrospective observational case series included patients with clinical OMMP who underwent conjunctival biopsy for DIF in at least 1 eye between 2018 and 2021 in an institutional setting. The primary outcome measures were association of age and chronic ocular complications with biopsy positivity. Of 61 patients, DIF positivity was seen in 33 (54.1%) clinically suspected cases of OMMP. Of 39 patients who underwent bilateral biopsy, 23 (59%) were positive, of which 12 (52%) were positive in both eyes while 11 (48%) were positive in 1 eye. Of 22 patients who underwent unilateral biopsy, 10 (45%) were positive. Of the 100 biopsied eyes, 45 (45%) were DIF positive. Among the immunoreactants studied, linear deposition of C3 was seen in all 45 positive eyes (100%). Increasing age was significantly associated with higher likelihood of biopsy negativity ( P = 0.032), whereas a greater Sotozono chronic ocular complication score, indicative of disease severity, was associated with low likelihood of biopsy positivity ( P = 0.0042) and lower overall expression of immunoreactants on DIF ( P = 0.0007). Older patients and patients with more severe ocular surface disease sequelae are likely to have negative DIF results. To optimize the chances of confirming the diagnosis of OMMP by DIF, both eyes should be biopsied early in the disease course. If 1 eye is being biopsied, the less affected eye must be chosen.

Cognitive Complaints and Their Impact on Daily Life in Patients with Degenerative Cerebellar Disorders

Cognitive and affective sequelae of cerebellar disease are receiving increased attention, but their actual rate of occurrence remains unclear. Complaints may have a significant impact on patients, affecting social behavior and psychological well-being. This study aims to explore the extent of subjective cognitive and affective symptoms in patients with degenerative ataxias in the Netherlands. An explorative study was set up in a heterogeneous group of degenerative ataxia patients. Self-reported cognition was evaluated in terms of executive functioning and affect (Dysexecutive Questionnaire/DEX), and memory/attention (Cognitive Failures Questionnaire/CFQ). The Daily Living Questionnaire (DLQ) was administered to quantify the impact on daily life. Furthermore, informants completed questionnaires to obtain insight into patients’ self-awareness and social cognition (Observable Social Cognition Rating Scale/OSCARS). This study shows that subjective complaints in the domains of (1) executive functioning and/or (2) memory and attention were reported by 29% of all patients (n = 24/84). In addition, more difficulties in daily life in terms of language/comprehension and community/participation were reported, and this was more common for patients with cognitive complaints than those without. Discrepancies between patients and informants about executive functioning were present in both directions. Deficits in social cognition were not identified at the group level, but more social-cognitive problems were observed in patients with more executive problems rated by informants. Taken together, our findings indicate that cognitive complaints are common in patients with degenerative cerebellar disorders and have an impact on daily life functioning. These results may help to increase awareness of cognitive symptoms and their impact in patients with cerebellar ataxia, their significant others, and professional caregivers.

Associations Between Plasma, Imaging, and Cerebrospinal Fluid Biomarkers with Driving Behavior and Cognitive Tests: Implications for Biomarker Usefulness.

Declines in instrumental activities of daily living like driving are hallmarks sequelae of Alzheimer's disease (AD). Although driving has been shown to be associated with traditional imaging and cerebrospinal fluid (CSF) biomarkers, it is possible that some biomarkers have stronger associations with specific aspects of driving behavior. Furthermore, associations between newer plasma biomarkers and driving behaviors are unknown. This study assessed the extent to which individual plasma, imaging, and CSF biomarkers are related to specific driving behaviors and cognitive functions among cognitively normal older adults. We analyzed naturalistic driving behavior from cognitively healthy older drivers (N = 167, 47% female, mean age = 73.3 years). All participants had driving, clinical, and demographic data and completed biomarker testing, including imaging, CSF, and/or plasma, within two years of study commencement. AD biomarkers were associated with different characteristics of driving and cognitive functioning within the same individuals. Elevated levels of plasma Aβ40 were associated with more speeding incidents, higher levels of CSF tau were related to shorter duration of trips, and higher CSF neurofilament light chain values were associated with traveling shorter distances, smaller radius of gyration, and fewer trips at night. We demonstrated that plasma, like CSF and imaging biomarkers, were helpful in predicting everyday driving behaviors. These findings suggest that different biomarkers offer complementary information with respect to driving behaviors. These distinct relationships may help in understanding how different biological changes that occur during the preclinical stage of AD can impact various sensorimotor and cognitive processes.

Charcot Neuroarthropathy of the Foot and Ankle in the Acute Setting: An Illustrative Case Report and Targeted Review.

Charcot neuroarthropathy (CN) is a rare but serious sequela of diabetes and other diseases that cause peripheral neuropathy. It is most commonly characterized by degeneration of the foot and/or ankle joints leading to progressive deformity and altered weight-bearing. If left untreated, the deformities of CN lead to ulceration, infection, amputation, and even death. Because of the associated peripheral neuropathy and proprioception deficits that accompany CN, patients typically do not perceive the onset of joint destruction. Moreover, in the hands of the untrained clinician, the initial presentation of CN can easily be mistaken for infection, osteoarthritis, gout, or inflammatory arthropathy. Misdiagnosis can lead to the aforementioned serious sequelae of CN. Thus, an early accurate diagnosis and off-loading of the involved extremity, followed by prompt referral to a specialist trained in the care of CN are crucial to prevent the late-term sequelae of the disease. The purpose of this article was to create an opportunity for enhanced understanding between orthopedic surgeons and emergency physicians, to improve patient care through the optimization of diagnosis and early management of CN in the emergent setting.

Real-World Clinical Characterisation of Polycythaemia Vera Patients from a Prospective Registry in Portugal: Is Resistance to Hydroxyurea a Reality?

Patients with polycythaemia vera (PV) are at increased risk of thrombosis and haemorrhages. Although hydroxyurea (HU) has been the frontline therapy for patients at high risk of vascular complications, about 25% of patients develop resistance/intolerance to this therapy. The aim of this non-interventional, multicentre cohort study was to understand the clinical characteristics and HU treatment response of Portuguese PV patients. HU resistance/intolerance was defined according to adjusted European LeukemiaNet (ELN) criteria. In total, 134 PV patients with a mean (SD) disease duration of 4.8 (5.0) years were included and followed up for 2 years. At baseline, most patients were ≥60 years old (83.2%), at high risk for thrombotic events (87.2%), and receiving HU therapy (79.1%). A total of 10 thrombotic events and 8 haemorrhagic events were reported, resulting in a 5-year probability of thrombo-haemorrhagic events of 17.2%. Haematocrit (p = 0.007), haemoglobin (p = 0.012) and MPN10 symptom score (12.0 (11.6) vs. 10.3 (9.1); p = 0.041) decreased significantly at the 24-month visit compared to baseline. Overall, 75.9% of patients met at least one of the adjusted ELN criteria for HU resistance, and 14.4% of patients remained on HU throughout the study. The results from this real-world study may help identify the subset of patients at higher risk for disease sequelae who may benefit from earlier second-line treatment.

Glycogen storage diseases.

Glycogen storage diseases (GSDs) are a group of rare, monogenic disorders that share a defect in the synthesis or breakdown of glycogen. This Primer describes the multi-organ clinical features of hepatic GSDs and muscle GSDs, in addition to their epidemiology, biochemistry and mechanisms of disease, diagnosis, management, quality of life and future research directions. Some GSDs have available guidelines for diagnosis and management. Diagnostic considerations include phenotypic characterization, biomarkers, imaging, genetic testing, enzyme activity analysis and histology. Management includes surveillance for development of characteristic disease sequelae, avoidance of fasting in several hepatic GSDs, medically prescribed diets, appropriate exercise regimens and emergency letters. Specific therapeutic interventions are available for some diseases, such as enzyme replacement therapy to correct enzyme deficiency in Pompe disease and SGLT2 inhibitors for neutropenia and neutrophil dysfunction in GSD Ib. Progress in diagnosis, management and definitive therapies affects the natural course and hence morbidity and mortality. The natural history of GSDs is still being described. The quality of life of patients with these conditions varies, and standard sets of patient-centred outcomes have not yet been developed. The landscape of novel therapeutics and GSD clinical trials is vast, and emerging research is discussed herein.