Clinical Management Research Articles

Lack of progress in cancer related outcomes after Liver Transplantation: Mitigating risk & identifying future needs to move this needle

Malignancy has a crucial impact on long-term survival after liver transplantation. There has been enhanced early detection rates with refined cancer screening and improved prognosis for many cancer diagnoses in the general population with the advent of targetted anti-cancer therapies. Similar advancements have not occurred in the transplant population over this same timeframe. Individualized strategies to reduce the risk of cancer, are needed in this high risk population. Strict adherence to screening and surveillance specific to the transplant population is required. Lifestyle modifications and medication management (both immunosuppressive and non-immunosuppressive) that may impact cancer risk and outcome are highlighted here. As more effective anti-cancer therapies evolve, transplant recipient access to these agents is paramount to truly impact cancer related outcomes in this population. With adequate immunosuppression, rejection rates with immunotherapy are lower than previously purported. Prospective studies of immunosuppression modifications needed to minimize rejection and maximize cancer response are ongoing and will reduce the fear from oncology and transplant providers alike, allowing utilization of the most optimal therapy available to the individual. This review aims to assess current data to aid in clinical management and identify the needs to fascilitate further progress in this field.

Adverse events associated with azithromycin and clarithromycin in adults aged ≥65: a disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) database

ABSTRACT Background Azithromycin and clarithromycin are commonly used to treat community-acquired pneumonia in adults aged ≥ 65, such as mycoplasma pneumonia. This study aims to evaluate adverse events (AEs) associated with azithromycin and clarithromycin in this age group by analyzing the FDA Adverse Event Reporting System (FAERS), providing insights for clinical use and management of AEs in this population. Research design and methods We retrieved reports of AEs related to azithromycin and clarithromycin from the FAERS database. Disproportionality analysis was conducted using the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Gamma Poisson Shrinkage (MGPS) to identify AEs associated with azithromycin and clarithromycin in adults aged ≥ 65. Results A total of 2,019 adverse event reports were retrieved for azithromycin, and 2,392 for clarithromycin. Off-label use (n = 349) and drug interactions (n = 487) were the most reported AEs in adults aged ≥ 65 for azithromycin and clarithromycin, respectively. Prolonged QT interval showed the strongest signal among AEs for azithromycin in this age group. Drug interaction-related medication errors had the strongest signal for clarithromycin. Seven signals not explicitly included in the azithromycin package insert were identified in adults aged ≥ 65. Fourteen signals not explicitly included in the clarithromycin package insert were identified. Conclusions Among adults aged ≥ 65, cardiac-related adverse events are more closely associated with azithromycin than with clarithromycin. Conversely, AEs related to drug interactions and psychiatric symptoms are more associated with clarithromycin. Additionally, clinicians should be vigilant regarding AEs not specified in the package inserts. The findings of this study may help optimize the selection of azithromycin and clarithromycin based on patient circumstances and assist clinicians in focusing on relevant AEs for early intervention.

Late-onset chylothorax after lung cancer surgery: clinical characteristics, management, and prevention.

The clinical characteristics and management of late-onset chylothorax after lung cancer surgery remained unknown. Here we aimed to provide evidence on the management of late-onset chylothorax by analysis of several cases with the largest sample size. We retrospectively collected clinical data of patients who developed late-onset chylothorax after lung cancer surgery and were re-admitted by a single surgeon in our center from 2016 to 2022. The clinical characteristics and management for these patients were analysed. The role of Hem-o-lok clipping after lymphadenectomy in preventing late-onset chylothorax was further explored by comparing the surgical outcomes between treated group and control group. A total of six patients who were re-admitted for late-onset chylothorax after lung cancer surgery were included for analysis. The mean age of them was 60.7 years old. The symptom of late-onset chylothorax was mainly dyspnea and cough and the diagnosis was all made by Sudan III staining between postoperative day 17 to 42. All patients were firstly treated with thoracocentesis and low-fat diet with intravenous nutrition. Four patients were successfully managed with low-fat diet and thoracocentesis, while the other two patients were further managed with pleurodesis with 50% glucose fluid solution. We found a significantly decreased risk of late-onset chylothorax in the treated group with improved procedure of applying Hem-o-lok clipping after lymphadenectomy than in the control group (0% versus 2.6%, P < 0.01). Late-onset chylothorax after lung cancer surgery was a rare and negligible complication, which may usually be managed by non-surgical methods. Hem-o-lok clipping during lymphadenectomy seemed to be an effective method to prevent late-onset chylothorax after lung cancer surgery.

Sputum Metabolomic Signature and Dynamic Change of Cough Variant Asthma.

Cough variant asthma (CVA), a common reason for chronic cough, is a globally prevalent and burdensome condition. The heterogeneity of CVA and a lack of knowledge concerning the exact molecular pathogenesis has hampered its clinical management. This study presented the first sputum metabolome of CVA patients, revealed the dynamic change during treatment, and explored biomarkers related to the occurrence and treatment response of CVA. We found arginine biosynthesis, purine metabolism, and pyrimidine metabolism pathways were enriched in CVA compared to healthy controls. Part of metabolic disturbances could be reversed by anti-asthmatic medication. The levels of dipeptides/tripeptides (alanyltyrosine, Gly-Tyr-Ala, Ala-Leu, and Thr-Leu) were significantly associated with sputum Neu% or Eos% of CVA patients. Differential metabolites pre-treatment between effective and ineffective groups enriched in purine metabolism, thiamine metabolism, and arginine metabolism. 2-isopropylmalate was down-regulated in CVA patients and increased after treatment, and effective group had a lower 2-isopropylmalate level pre-treatment. Random forest and logistic regression models identified glutathione, thiamine phosphate, alanyltyrosine, and 2'-deoxyadenosine as markers for distinguishing CVA from healthy controls (all AUC > 0.8). Thiamine phosphate might also be promising for predicting therapy responsiveness (AUC = 0.684). These findings implied that disturbed mitochondrial energy metabolism and imbalanced oxidation-reduction homeostasis probably underlay the metabolic pathogenesis of CVA.

Clinical Characteristics, Management, and Outcomes of Bacteremia in Children with Cancer: A Retrospective Study

Abstract Background Bacteremia is a common infectious complication among pediatric oncology patients, yet management practices are not standardized. Antibiotic treatment courses as short as seven days are supported by literature and could improve patient quality of life and resource use. However, it is not known if short courses are associated with greater treatment failure in immunocompromised patients. Methods We conducted a retrospective study at St. Jude Children’s Research Hospital, including patients with a laboratory confirmed bloodstream bacterial infection between April 1, 2022, and March 31, 2023. Clinical characteristics such as age, gender, type of malignancy, phase of treatment, underlying chronic conditions, and clinical sites of infection were collected. Antibiotics used, duration of therapy, and route of administration were also gathered to examine clinical management. Clinical outcomes were measured by documenting ICU admission, oxygen, fluid and vasopressor requirements, date of hospital discharge, bacteremia recurrence, and mortality. Results 86 patients contributed 112 bacteremia episodes that met eligibility criteria. Severe neutropenia was present at onset in 68% of all episodes and 32% of patients did not have neutrophil recovery over 500 cells/ml during the episode. Gram-negative organisms accounted for 52% of isolated organisms, with the most common organisms isolated overall being Escherichia coli (19%), followed by Klebsiella pneumoniae (14%), and Viridans group streptococcus (14%). The median length of antibiotic treatment was 12 days. Treatment duration was not associated with oncologic diagnosis or Gram-negative versus Gram-positive infection. Conclusion Bacteremia occurs more frequently in patients who are neutropenic, especially those who are severely neutropenic with an absolute neutrophil count less than 500 cells/mL. Treatment duration is not associated with primary cancer diagnosis or type of bacteremia. In this single high resource setting, bloodstream infections resulted in significant morbidity, resource use, and a mortality rate of 8%, highlighting opportunities for investigation to improve clinical practices.

Radiculomegaly as a key clinical feature in oculo-facio-cardio-dental (OFCD) syndrome: a case report with a novel truncating variant in BCOR gene.

Radiculomegaly is a rare dental anomaly characterised by the enlargement of the root canals of teeth. It is usually associated with oculo-facio-cardio-dental (OFCD) syndrome due to truncating variants in BCL-6 transcriptional corepressor (BCOR) (MIM*300485). We present the case of a 21-year-old female patient who was referred to genetics for a polymalformative syndrome including bilateral glaucoma and dental anomalies, especially radiculomegaly. Some others dysmorphic features were right superior lip notch, ogival palate, long philtrum, difficulty in pronation, café-au-lait spots, II-III toe bilateral syndactyly, and macrocephaly. Cone-beam CT confirmed radiculomegaly. The genetic analysis identified a heterozygous pathogenic variant NM_001123385.1:c.2093del (p.Pro698Glnfs*17) in the BCOR gene. After genetic diagnosis of OFCD syndrome, cardiac CT-scan revealed a large asymptomatic atrial septal defect that was subsequently surgically closed. Reviews of the literature have previously highlighted the prevalence of radiculomegaly in OFCD syndrome with a positive predictive value of 88.23% and a sensitivity of 75.94%. This case report highlights the importance of radiculomegaly as a clinical sign of OFCD syndrome, emphasising the rarity of non-syndromic radiculomegaly and the benefits of its diagnosis in clinical management, especially in cardiac screening.

Gestational diabetes: an update sixty years after O'Sullivan and Mahan.

Sixty years after the landmark publication by O'Sullivan and Mahan, the current paper seeks to review and place into context the importance of gestational diabetes (GDM) both as a marker of increased risk of adverse maternal and fetal pregnancy outcomes and as an indicator of future maternal and infant health risks. We review the evolution of GDM as a diagnosis, the ongoing debate regarding diagnostic approaches, the underlying pathophysiology, the epidemiology and the importance of GDM in the context of the global epidemics of diabetes and obesity. Focusing on clinical management, we review lifestyle based therapy and pharmacotherapy for GDM, consider obstetric management and outline the short term and lifelong health risks posed by a GDM diagnosis.

Oral syphilis - the great imitator: a series of six cases

Syphilis is an infectious disease which can present with multitudinous mucocutaneous manifestations. Often referred to as the ‘great mimicker', syphilis can present with non-specific symptoms and has a tropism for various organ systems. The oral cavity has been identified as a site commonly affected in the early stages of syphilis infection. Identification of the diverse presentations seen across the different stages of syphilis infection can assist in early diagnosis and treatment for this cohort of patients. Despite accurate diagnostic tools and the susceptibility of the infection to standard antimicrobial therapy, syphilis infections continue to rise worldwide.We present the clinical features and management of six cases of oral syphilis who presented to our unit. One case presented in 2008, but the other five cases presented between 2016 and 2023, reflecting the increasing incidence of syphilis infection. Five cases presented in the secondary stage of the infection while one presented with a primary infection in the form of a single chancre.The documented cases demonstrate the non-specific and variable clinical features of oral syphilis and highlight the importance of awareness in the dental profession of these manifestations. Dentists have an important role to play in recognising the disease and arranging appropriate testing for early intervention. This will not only reduce the incidence of the devastating consequences of tertiary infections but will also result in reduced spread of the disease.

Symptomatic Nonstenotic Carotids: A Topical Review.

Historically, the management of carotid artery disease has primarily focused on the degree of stenosis as the main indicator for assessing stroke etiology, risk, and need for intervention. However, accumulating evidence suggests that structural and biological features within the arterial wall, such as intraplaque hemorrhage, may have superior diagnostic, prognostic, and therapeutic values. Under current guidelines, unless an atheroma results in ≥50% stenosis, it is not considered the cause of a cerebrovascular event. This results in extensive and often unproductive diagnostic workup, prescription of ineffective medical therapy, and preclusion of patients from receiving revascularization procedures that have been shown to prevent recurrent cerebrovascular events in cases of ≥50% stenosis. A subset of embolic strokes of undetermined source, which account for up to 25% of all ischemic cerebrovascular events, are thought to be due to thromboembolic phenomena from undiagnosed plaque disruptions in nonstenotic arteries (<50% stenosis). Recently, it has been proposed to reclassify this subgroup of patients as symptomatic nonstenotic carotid if the carotid plaque ipsilateral to the cerebrovascular event presents with high-risk features including intraplaque hemorrhage, lipid-rich necrotic core, thinning/rupture of the fibrous cap, and ulceration. In this review, we first provide a historical overview of the chain of events and circumstances that resulted in the present management of carotid artery disease. Second, we embed the contemporary biomarkers of plaque vulnerability in a modern mechanistic paradigm of carotid plaque disruption and thromboembolization. Third, we review the clinically available imaging tools to detect these biomarkers, and how their use has started to shed light on the prevalence and natural history of this underdiagnosed condition. Fourth, we review recent clinical studies employing a contemporary definition of symptomatic nonstenotic carotid and discuss targeted treatments for this condition. Finally, we make a case to generate the much-needed high-level evidence to align the clinical management of patients with symptomatic nonstenotic carotid with a contemporary understanding of plaque disruption and thromboembolization.

Blended Phenotypes From a SERPINA 11 Pathogenic Variant Over Underlying Immune Fetal Hydrops: A Rare Case Report and Literature Review

Abstract Fetal hydrops can stem from immune or nonimmune causes. Immune causes often involve red cell alloimmunization, whereas nonimmune causes encompass structural malformations, aneuploidy, infections, lymphatic system disorders, genetic syndromes, and more. In a rare and complex case, we encountered a fetal hydrops presentation characterized by blended phenotypes, indicating both a genetic and an underlying immune etiology. The mother, Rhesus negative, presented with a history of adverse obstetric events. At 21 weeks, the current fetus was diagnosed with hydrops. Maternal blood tests unveiled Rhesus alloimmunization, featuring a positive indirect Coombs test at a 1:512 dilution and the presence of anti-D, anti-C, and anti-E antibodies. Fetal blood sampling revealed an O-positive blood group with a hemoglobin level of 10 gm/dL. Despite administering intrauterine transfusion to the fetus, there was no improvement; instead, the fetal hydrops worsened, accompanied by the emergence of nuchal and axillary masses. Exome sequencing of fetal DNA revealed the fetus was homozygous for a pathogenic variant in the SERPINA11 gene and compound heterozygous for a pathogenic variant in the PIEZO1 gene. Furthermore, the combination of pathogenic variants in SERPINA11 and PIEZO1 genes has not been described in cases of fetal hydrops before. This case posed significant challenges in management due to the concurrent presence of both immune and nonimmune hydrops. We describe some of the diagnostic challenges faced in clinical management of this case.

Case Report: Charcot-marie-tooth disease caused by a de novo MORC2 gene mutation - novel insights into pathogenicity and treatment

Charcot-Marie-Tooth disease (CMT) is a hereditary peripheral neuropathy involving approximately 80 pathogenic genes. Whole-exome sequencing (WES) and confirmatory Sanger sequencing analysis was applied to identify the disease-causing mutations in a Chinese patient with lower limb weakness. We present an 18-year-old male with a 2.5-year history of progressive lower limb weakness and an unsteady gait. Upon admission, a physical examination revealed hands tremulousness, bilateral calf muscle wasting and weakness, pes cavus, and elevated serum creatine kinase (CK) levels. Electromyography demonstrated axonal neuropathy affecting both upper and lower limbs. A de novo heterozygous missense mutation was identified in the MORC2 gene, NM_001303256.3: c.1199A&amp;gt;G, NP_001290186.1: p.Gln400Arg. Consequently, these clinical and genetic findings suggested a diagnosis of hereditary peripheral neuropathy, CMT type 2Z. Oral mecobalamin and coenzyme Q10 was initiated as subsequent treatment. Our study firstly reports the MORC2 c.1199A&amp;gt;G mutation occurring de novo, highlighting its causal association with CMT2Z, and prompting its reclassification as likely pathogenic. Oral mecobalamin and coenzyme Q10 might be a potential treatment approach for early-stage CMT2Z. We recommend genetic testing for CMT patients to identify the genetic etiology, thereby improving clinical management and facilitating genetic counseling.

Deubiquitylase USP52 Promotes Bladder Cancer Progression by Modulating Ferroptosis through Stabilizing SLC7A11/xCT.

Bladder cancer (BLCA) is a prevalent cancer with high case-fatality rates and a substantial economic burden worldwide. Understanding its molecular underpinnings to guide clinical management is crucial. Ferroptosis, a recently described non-apoptotic form of cell death, is initiated by the lethal accumulation of iron-dependent lipid peroxidation products. Despite growing interest, the roles and vulnerabilities determining ferroptosis sensitivity in BLCA remain unclear. Re-analysis of single-cell RNA data reveals a decrease in high-ferroptosis cancer cells as BLCA advances. USP52/PAN2 is identified as a key regulator of ferroptosis in BLCA through an unbiased siRNA screen targeting 96 deubiquitylases (DUBs). Functionally, USP52 depletion impedes glutathione (GSH) synthesis by promoting xCT protein degradation, increasing lipid peroxidation and ferroptosis susceptibility, thus suppressing BLCA progression. Mechanistically, USP52 interacts with xCT and enzymatically cleaves the K48-conjugated ubiquitin chains at K4 and K12, enhancing its protein stability. Clinical BLCA samples demonstrate a positive correlation between USP52 and xCT expression, with high USP52 levels associated with aggressive disease progression and poor prognosis. In vivo, USP52 depletion combined with ferroptosis triggers imidazole ketone Erastin (IKE) synergistically restrains BLCA progression by inducing ferroptosis. These findings elucidate the role of the USP52-xCT axis in BLCA and highlight the therapeutic potential of targeting USP52 and ferroptosis inducers in BLCA.

Removable partial dentures: Part 1.

The provision of removable partial dentures (RPDs) is an important skill for practitioners and it can often be challenging to make a successful prosthesis which the patient finds satisfactory. This three-part series has been designed to provide an overview of the clinical management of patients requiring RPDs. This first part provides a refresher of the aspects of the history and examination that are relevant to RPDs. We describe some key principles that are relevant to challenging denture cases. This will help the reader begin the treatment planning process and understand some of the factors which influence the prognosis of dentures.

Oxytocin/Oxytocin Receptor Signalling in the Gastrointestinal System: Mechanisms and Therapeutic Potential

The neuropeptide hormone oxytocin (OT) is involved in various physiological and pathological processes via the oxytocin receptor (OTR). While OT is most widely known as a reproductive system hormone and a nervous system neurotransmitter, the OT/OTR system has gradually gained much attention for its role in the gastrointestinal (GI) system, such as the GI motility, secretion, and bowel inflammatory reactions. Its importance in GI cancers has also been reported in the past few decades. The promising clinical observations have revealed OT’s anti-nociceptive effect, protective effect over gut injury, and the potential of using microbiota to naturally increase endogenous OT levels, which shed a light on the management of GI disorders with lower side effects. However, no current comprehensive review is available on the actions of OT/OTR in the GI tract. This review aims to present the lesser-known role of the OT/OTR system in the GI tract, and the most recent findings are discussed regarding the distribution and functional role of OTR signalling in regulating (patho)physiological functions of the GI tract. Special emphasis is placed on its therapeutic potential for clinical management of GI disorders, such as GI pain, inflammatory bowel disease (IBD), and irritable bowel syndrome (IBS). The recent characterisation of the OTR’s crystal structure has advanced research for designing and identifying new OTR-specific molecules. Future in-depth basic and clinical research is needed to further elucidate the involvement and detailed mechanism of OT/OTR in GI disorders, and the development of OTR-specific ligands.

A Multicenter, Longitudinal Maternal and Birth Cohort Study in Latin America to Assess Prevalent Respiratory Tract Infections in Children from 0 to 5 Years of Age. The MINERVAL Study

Abstract Background A maternal and birth cohort study can assess the etiology and clinical course of lower respiratory tract infections and offers the opportunity to evaluate the relationship between sociodemographic, clinical, host characteristics and disease severity. In Latin America, a consortium of clinical research centers in Colombia and Panama has demonstrated its ability to conduct long-term longitudinal studies involving active surveillance of thousands of children with consistent retention rates. The MINERVAL cohort study aims to estimate the incidence, etiology, severity, and burden of lower respiratory tract infections (LRTI) and to identify microbiome and transcriptome profiles to help predict risk and assess disease severity in children from birth to 5 years of age. Methods We are establishing a maternal/birth cohort study in four sites (Cali, Bogota, Barranquilla and Panama), and will be recruiting 542 participants per center. Enrolled pregnant women between 24 and 27 weeks of gestation, and newborns under 4 weeks of age, will be closely followed with active surveillance weekly during the first 2 years for early detection of LRTI. Monthly telephone follow-up calls will continue until five years of age to assess the development of long-term respiratory morbidity and complications, including recurrent wheezing episodes. Clinical samples (NP swabs -for respiratory pathogen detection and microbiome analysis-, and blood -for cytokine and transcriptome analysis-) will be obtained in pregnant women, and in infants in the first 4 weeks of life and every 6 months for two years. Women and children who develop LRTI during the longitudinal follow-up will be evaluated clinically and samples will be collected. Results This cohort will provide prospective data and biological samples at crucial stages of children’s development, to allow estimation of the incidence and burden of LRTI by age and etiology, and the identification of risk factors and possible targets for intervention. Furthermore, the use of transcriptional profiling will allow early identification of variables to predict and guide clinical management in children, the use of antivirals and monoclonal antibodies, and to prioritize the population to be vaccinated according to age and risk factors. Conclusion The establishment of observational maternal and birth cohorts in Latin America could provide information to guide the development of strategies to prevent and mitigate the impact of respiratory tract infections in young children. Collaboration among investigators in the region and partnerships with international investigators optimizes resources and allows standardization of good surveillance practices, data exchange and the generation of new knowledge for future studies.

Comparison of Clinical Diagnosis and Autopsy Findings of Early Neonatal Deaths: Diagnostic Challenges and the Value of Autopsy in Identifying Rare Pathologies.

In a non-forensic hospital setting, neonatal death within the first week of life is often related to premature birth and/or lung diseases. Without post-mortem examination, the identification of the cause of death may be challenging. Autopsy can confirm the clinical diagnosis, uncover additional information or change the diagnosis. Our study aimed to assess the correlation between the clinical diagnosis and post-mortem findings in early neonatal deaths. The retrospective study included autopsy cases with neonatal deaths within the first 7 days of life (arbitrary time interval 2006-2021). Discrepancies between clinical and histopathological findings were classified into 3 groups: (i) full agreement, (ii) additional findings discovered by autopsy, or (iii) autopsy changed the diagnosis. A cohort of 27 cases could be identified and lung pathologies were the most common finding (56%). Additional findings could be discovered in 48% of cases. Major discrepancies which changed the clinical diagnosis could be found in 11% (n = 3/27) of cases. Frequently, post-mortem examinations validate the clinical diagnosis while revealing crucial information in a few cases. In these discrepant cases, autopsy findings can provide information for genetic counselling and quality control of clinical management.

Studying Contact Replays: Investigating Mechanisms, Management and Game Exposures (SCRIMMAGE) for brain health in the Australasian National Rugby League: a protocol for a database design

Concussions in contact sports are challenging for athletes, health professionals and sporting bodies to prevent, detect and manage. Design of interventions for primary prevention, early recognition of concussion and continuing...

Matching clinical and genetic data in pediatric patients at risk of developing cystic kidney disease.

Cystic kidney disease is a heterogeneous group of hereditary and non-hereditary pathologic conditions, associated with the development of renal cysts. These conditions may be present both in children and adults. Cysts can even be observed already during the prenatal age, and pediatric patients with cysts need to be clinically monitored. An early clinical and genetic diagnosis is therefore mandatory for optimal patient management. The aim of this study was to perform genetic analyses in patients with echographic evidence of kidney cysts to provide an early molecular diagnosis. A cohort of 70 pediatric patients was enrolled and clinically studied at the time of first recruitment and at follow-up. Genetic testing by clinical exome sequencing was performed and a panel of genes responsible for "cystic kidneys" was analyzed to identify causative variants. Sanger validation and segregation studies were exploited for the final classification of the variants and accurate genetic counseling. Data showed that 53/70 of pediatric patients referred with a clinical suspicion of cystic kidney disease presented a causative genetic variant. In a significant proportion of the cohort (24/70), evidence of hyper-echogenic/cystic kidneys was already present in the prenatal period, even in the absence of a positive family history. This study suggests that cystic kidney disease may develop since the very early stages of life and that screening programs based on ultrasound scans and genetic testing play a critical role in diagnosis, allowing for better clinical management and tailored genetic counseling to the family.

Chromosome 8p Syndromes Clinical Presentation and Management Guidelines.

Rearrangements of the p-arm of Chromosome 8 can result in a spectrum of neurodevelopmental challenges, along with increased risk of epilepsy, structural brain and cardiac malformations, persisting developmental delays, and other health challenges. The majority of patients reported on in this sample are characterized by an inverted-duplication deletion rearrangement, but deletions, duplications, and mosaic ring changes in 8p result in similar phenotype. In this report, we add to the phenotypic and functional description of these patients according to their specific chromosomal rearrangement, share neuro-psychometric values, and propose surveillance care guidelines for caregivers and medical providers of patients with Chromosome 8p Syndromes. Observations from clinical experience with 24 patients seen at our 8p-dedicated Multi-Disciplinary Neurogenetics program are shared.

Insights, recommendations, and research priorities for central sleep apnea: report from an expert panel.

Central sleep apnea (CSA) is commonly encountered among patients with sleep-disordered breathing, however its clinical consequences are less well-characterized. We therefore convened an expert panel to discuss the common presentations of CSA, as well as challenges and knowledge gaps in the diagnosis and management of CSA. The panel identified several key research priorities essential for advancing our understanding of the disorder. Within the diagnostic realm, panel members discussed the utility of multi-night assessments, and importance of the development and validation of novel metrics and automated assessments for differentiating central versus obstructive hypopneas, such that their impact on clinical outcomes and management may be better evaluated. The panel also discussed the current therapeutic landscape for the management of CSA and agreed that therapies should primarily aim to alleviate sleep-related symptoms, after optimizing treatment to address the underlying cause. Most importantly, the panel concluded that there is a need to further investigate the clinical consequences of CSA, as well as the implications of therapy on clinical outcomes, particularly among those who are asymptomatic. Future research should focus on endo-phenotyping central events for a better mechanistic understanding of the disease, validating novel diagnostic methods for implementation in routine clinical practice, as well as the use of combination therapy and comparative effectiveness trials in elucidating the most efficacious interventions for managing CSA.