Additional Symptoms Research Articles

NCOG-11. FACTORS PREDICTING SPEECH AND GAIT RECOVERY IN CHILDREN WITH POST-OPERATIVE POSTERIOR FOSSA SYNDROME (PFS)

Abstract Posterior fossa syndrome/cerebellar mutism syndrome is a surgical complication of posterior fossa tumor resection, especially midline tumors. Initially thought to involve complete mutism, PFS is now recognized as a complex syndrome involving loss of language (complete [PFS1] and incomplete [PFS2]). Additional symptoms include apraxia, movement disorder, motor and coordination deficits, and emotional lability. The aim of this study was to identify factors that influence delayed speech and independent gait recovery in children with PFS. We prospectively studied 73 children ≥3 years of age with medulloblastoma who developed PFS (SJMB12, NCT01878617). Enrolled children received standardized neurologic examinations and serial imaging before, during and up to five years after completion of therapy. Neurological examinations included scale for assessment and rating of ataxia (SARA), CTCAE grading of neurologic deficits, and severity of injury to the superior cerebellar peduncles (SCP) on post-operative MRI. Median time to speech recovery was 1.4 months (range 0.3-14.3); 81% had return of speech at 3 months and 97% at 12 months. On multivariable Cox regression analysis, complete mutism (HR 0.17, p<0.0001) and inability to sit (HR 0.40, p=0.001) were associated with delayed speech return. Independent ambulation was regained by 80.8% at a median of 2.3 (range 0.3-71.3) months. 70% had a return of ambulation at 12 months and 77% at 24 months. On multivariable Cox regression analysis, complete mutism (HR 0.32, p=0.016), inability to sit (HR 0.30, p=0.002), SARA score (HR 0.94, p=0.002), and right SCP injury (HR 0.47, p=0.014) were significantly associated with delayed return of ambulation. Presence of mutism, inability to sit unassisted, higher SARA score, and right SCP injury at the time of PFS diagnosis are associated with time to recovery of speech/language and ambulation. Our findings have prognostic implications for families and to help identify children in need of more intensive interventions.

Collecting Real-Time Patient-Reported Outcome Data During Latent Labor: Feasibility Study of the MyCap Mobile App in Prospective Person-Centered Research

Background The growing emphasis on patient experience in medical research has increased the focus on patient-reported outcomes and symptom measures. However, patient-reported outcomes data are subject to recall bias, limiting reliability. Patient-reported data are most valid when reported by patients in real time; however, this type of data is difficult to collect from patients experiencing acute health events such as labor. Mobile technologies such as the MyCap app, integrated with the REDCap (Research Electronic Data Capture) platform, have emerged as tools for collecting patient-generated health data in real time offering potential improvements in data quality and relevance. Objective This study aimed to evaluate the feasibility of using MyCap for real-time, patient-reported data collection during latent labor. The objective was to assess the usability of MyCap in characterizing patient experiences during this acute health event and to identify any challenges in data collection that could inform future research. Methods In this descriptive cohort study, we quantified and characterized data collected prospectively through MyCap and the extent to which participants engaged with the app as a research tool for collecting patient-reported data in real time. Longitudinal quantitative and qualitative surveys were sent to (N=18) enrolled patients with term pregnancies planning vaginal birth at Oregon Health Sciences University. Participants were trained in app use prenatally. Then participants were invited to initiate the research survey on their personal smartphone via MyCap when they experienced labor symptoms and were asked to return to MyCap every 3 hours to provide additional longitudinal symptom data. Results Out of 18 enrolled participants, 17 completed the study. During latent labor, 13 (76.5%) participants (all those who labored at home and two-thirds of those who were induced) recorded at least 1 symptom report during latent labor. A total of 191 quantitative symptom reports (mean of 10 per participant) were recorded. The most commonly reported symptoms were fatigue, contractions, and pain, with nausea and diarrhea being less frequent but more intense. Four participants recorded qualitative data during labor and 14 responded to qualitative prompts in the postpartum period. The study demonstrated that MyCap could effectively capture real-time patient-reported data during latent labor, although qualitative data collection during active symptoms was less robust. Conclusions MyCap is a feasible tool for collecting prospective data on patient-reported symptoms during latent labor. Participants engaged actively with quantitative symptom reporting, though qualitative data collection was more challenging. The use of MyCap appears to reduce recall bias and facilitate more accurate data collection for patient-reported symptoms during acute health events outside of health care settings. Future research should explore strategies to enhance qualitative data collection and assess the tool’s usability across more diverse populations and disease states.

New onset of ataxic dysarthria with CSF overdrainage syndrome: A case report

Cerebrospinal fluid (CSF) overdrainage syndrome occurs when excessive CSF drainage from the cranial cavity results from a spinal CSF leak or overdrainage through a ventriculoperitoneal (VP) or lumboperitoneal (LP) shunt. Symptoms include severe orthostatic headache, worsening with sitting or standing but improving when recumbent. The headache is typically dull, throbbing, and bilateral and may be exacerbated by Valsalva maneuver, coughing, or straining. Additional symptoms can include dizziness, nausea, vomiting, gait disturbances, diplopia, back pain, and seizures. We present a case of overdrainage syndrome following LP shunt placement for idiopathic intracranial hypertension in a 38-year-old woman with Ehlers–Danlos syndrome (EDS). One year post-surgery, she reported worsening headaches and nausea after prolonged upright positioning. Neurological examination revealed cerebellar dysfunction, including dysdiadochokinesia, intention tremor, and ataxic dysarthria. This condition gradually emerged 6 months post-LP shunt placement and was attributed to chronic overdrainage. After 1 day of observation, the patient underwent surgery to clamp the LP shunt outflow, resulting in overnight symptom resolution, including ataxic speech. This case underscores the importance of recognizing ataxic dysarthria in conjunction with low intracranial pressure syndromes, particularly in patients with EDS. It emphasizes the need to be aware of the diverse clinical manifestations of EDS and their relationship to altered CSF pressure syndromes.

T-cells are significantly reduced in the luminal gastrointestinal tract of patients with “complete” 22q11.2 deletion syndrome (DiGeorge syndrome): Utilization of chromogenic multiplex immunohistochemistry to define cellular populations

Patients with 22q11.2 deletion syndrome or DiGeorge syndrome commonly report gastrointestinal symptoms in addition to more widely understood cardiac and immunodeficiency abnormalities. However, the morphologic features of gastrointestinal tract pathology in these patients are poorly understood. We previously reported that plasma cells are essentially absent from the luminal gastrointestinal tract of patients with “complete” DiGeorge syndrome. Herein, we add to the current understanding of the luminal gastrointestinal tract changes in patients with DiGeorge syndrome. Patients with cytogenetically confirmed DiGeorge syndrome were identified after approval from our institutional review board. Gastrointestinal tract biopsies from patients with DiGeorge syndrome that were severely immunosuppressed (complete DiGeorge syndrome, DGS-I), partially immunocompromised (partial DiGeorge syndrome, DGS), and from control patients were reviewed. Two panels of chromogenic multiplex immunohistochemistry (IHC) were performed to evaluate the immune cell infiltrate in the lamina propria of the duodenum and colon. “Panel #1” was composed of antibodies targeting CD3, CD20, and CD68. “Panel #2” was composed of antibodies targeting CD4, CD8, CD56, and TCRϒδ. Assessment of cell types identified by these antibody targets demonstrated a significant reduction of duodenal and colonic T-cells in patients with complete DiGeorge syndrome. In addition to establishing the morphologic phenotype of the luminal gastrointestinal tract of patients with DiGeorge syndrome, we also highlight our chosen technology of chromogenic multiplex IHC as a relatively accessible research and diagnostic tool with wide potential to be utilized across various disease processes.

P04 A vexing case of polymyalgia rheumatica

Abstract Introduction VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a recently described autoinflammatory condition characterised by somatic mutations in the UBA1 gene, resulting in significant morbidity. Disease presentation can mimic several rheumatological conditions, delaying diagnosis and appropriate management. This case report presents the clinical course of a patient with a complex history of musculoskeletal symptoms and systemic inflammation, first diagnosed with polymyalgia rheumatica (PMR), who was later identified as having VEXAS syndrome almost six years after first referral to the rheumatology clinic. It illustrates the importance of considering rare autoinflammatory conditions in patients with atypical presentations of common rheumatological disorders. Case description A 76-year-old gentleman was referred from the haematology clinic where he had undergone investigation for pancytopenia and raised inflammatory markers. Initial investigations under the haematology team revealed normal CT chest, abdomen and pelvis, unremarkable bone marrow biopsy and cytogenetics. He presented with muscle stiffness and proximal limb girdle pain. Additional symptoms included fatigue and a diffuse non-specific erythematous rash. There was no significant past medical history and he was previously very fit and active. Rheumatology investigations were normal, apart from persistently elevated inflammatory markers (ESR 86 mm/h and CRP 70 mg/L). A diagnosis of polymyalgia rheumatica was made and prednisolone 15 mg was started. Although he initially had a good response to this, he continued to experience significant inflammatory and constitutional symptoms. These included small joint polyarthritis, night sweats and weight loss. He was pancytopenic with associated reduced exercise tolerance, requiring transfusions and erythropoietin. To exclude other differentials, a repeat bone marrow biopsy was performed. This revealed dysplasia likely secondary to underlying inflammation, although no clonal abnormalities or vacuoles were detected. MRI right hand showed synovitis, and he was therefore treated for myalgic-onset rheumatoid arthritis. Prednisolone dose was increased temporarily and methotrexate was added, resulting in temporary improvement of his ESR 16 mm/h and CRP 25 mg/L. The patient continued to have ongoing constitutional symptoms and developed new ataxia. Further investigations, including MRI head, gastroscopy and Whipple’s PCR were all normal. Repeat CT chest, abdomen and pelvis and PET-CT were unremarkable. His symptoms and inflammatory markers were responsive to steroids. Given his symptoms and macrocytosis, he was tested for ubiquitin-activating enzyme UBA1 gene which was positive, confirming the diagnosis of VEXAS syndrome. Methotrexate was stopped due to worsening cytopenia, prednisolone continued and tocilizumab started. He showed significant improvement in pancytopenia and symptoms following initiation of tocilizumab. Discussion VEXAS is characterised by somatic mutations in the UBA1 gene; its pathogenesis leads to malfunctioning methionine-41, an enzyme that initiates ubiquitylation. This leads to increased activation of innate immune pathways and induces systemic inflammation, manifesting in a variable clinical presentation. This variability makes the diagnosis challenging and leads to a median diagnostic delay of 5.5 years, similar to our patient’s six-year delay. Our patient was initially managed as PMR due to his clinical presentation and lack of an obvious alternative diagnosis. This misdiagnosis is not unique. Often, patients later diagnosed with VEXAS are first managed as either inflammatory conditions, notably polychondritis, vasculitis or Sweet’s syndrome, or myelodysplastic syndrome (MDS). VEXAS is hallmarked by haematological dysfunction as much as it is by inflammatory features. In fact, our patient’s first signs included a mild cytopenia which later developed into a progressive macrocytic anaemia. This is classical of VEXAS. Other haematological manifestations include thrombotic events and MDS, with minimal response to EPO-stimulating agents as seen here. His ongoing deterioration triggered an alternative diagnosis to be sought. VEXAS is unusual as an autoinflammatory disease: its causative mechanism is a somatic mutation acquired later in life. Its diagnosis can be confirmed by inactivation of the x-linked UBA1 gene. This case highlights the need for UBA1 testing when dealing with an unexplained inflammatory phenotype, especially in men with cytopenia, multiorgan autoinflammation or MDS-like features. VEXAS presents a management challenge. The term ‘haeamatoinflammatory’ has been created to reflect its unique nature, warranting input from both specialist teams as well as the wider MDT. Key learning points • VEXAS should be considered as a differential when dealing with unexplained inflammatory symptoms, especially in men, multiorgan autoinflammation, vasculitis and/or MDS-like features. • VEXAS is often progressive and transfusion-dependence is associated with a poorer prognosis. A macrocytic anaemia is a prominent feature of the condition. • The absence or low proportion of vacuoles in bone marrow should not prevent us from testing for VEXAS if clinically indicated. • No established protocols for VEXAS yet exist. Haematological management is supportive. Anti-inflammatory treatment is based on collective observed evidence, including the use of tocilizumbab (anti-IL6) and janus kinase (JAK) inhibitors. Allogenic haemopoietic stem cell transplantation has been successful in few patients and may represent an option for patients with severe disease.

Exercise and footwear in medial knee osteoarthritis: a randomized controlled trial comparing flat flexible footwear to stable supportive shoes

Abstract Objective This randomized controlled trial (RCT) investigated whether adding daily use of flat flexible footwear (FFF) to a strengthening and aerobic exercise programme improved short- and longer-term outcomes compared to adding stable supportive shoes (SSS) in people with medial tibiofemoral osteoarthritis (OA). Methods Participants (n = 97) with medial tibiofemoral OA were randomly assigned (1:1) to FFF (n = 50) or SSS (n = 47) group. Participants in both group received a 9-month intervention (3 months supervised followed by 6 months unsupervised exercise). The primary outcome was change in knee pain on walking at 3 months measured using a 11-point numeric rating scale (NRS). Secondary outcomes included change from baseline to 3 and 9 months in severity of knee pain overall (NRS), physical function (WOMAC subscale), habitual physical activity level (PASE), quality of life (QoL) (EQ-5D-5L), and markers of inflammation (Effusion- and Hoffa-synovitis) and structural disease progression (bone marrow lesions (BMLs)). Results There were no significant differences between the groups in the change in pain on walking (between-group difference, -0.67 [95% CI, -1.62 to 0.29]) at 3 months. Knee pain on walking and overall knee pain significantly decreased in both groups at 3 months and 9 months. Physical function and QoL improved in both groups at 3 months and at 9 months. We found no between-group differences in any secondary outcome at any time. Conclusions FFF added to exercise therapy did not provide additional better symptom- nor structure-modification benefit compared to conventional SSS and exercise in people with medial tibiofemoral OA. Clinical trial registration number ClinicalTrials.gov (NCT03796832)

Basic helix-loop-helix transcription factor BHLHE22 monoallelic and biallelic variants cause a neurodevelopmental disorder with agenesis of the corpus callosum, intellectual disability, tone and movement abnormalities.

BHLHE22 encodes a Class II basic helix-loop-helix transcription factor (bHLH). It is expressed exclusively in the retina and central nervous system (CNS), and functions as an important regulator of retinogenesis and neuronal differentiation. Mice lacking bhlhe22 show nearly complete loss of three brain comminsure, including the corpus callosum. Here we report eleven individuals from nine unrelated families with BHLHE22 variants, with a neurodevelopmental disorder presenting with absent or limited speech, severely impaired motor abilities, intellectual disability (ID), involuntary movements, autistic traits with stereotypies, abnormal muscle tone. The majority of individuals have partial or complete agenesis of the corpus callosum (ACC). Additional symptoms comprised epilepsy, variable dysmorphic features, and eye anomalies. One additional individual had spastic paraplegia without delayed development and ACC, expanding the phenotype to milder and later onset forms. Four individuals carry de novo missense variants within the highly conserved helix-loop-helix domain while seven individuals from five unrelated families carry a recurrent homozygous frameshift variant, p.(Gly74Alafs*18). Our findings implicate BHLHE22 variants in causing a previously unidentified autosomal dominant and recessive neurodevelopmental disorder associated with ACC, severe motor, language, and cognitive delays, abnormal tone, and involuntary movements. To our knowledge, this is the first report of Class II bHLH variants in humans shown to significantly disrupt brain development, cognition, and movement.

Organic changes of anal sphincter in complicated rectal fistulas

Aim. To evaluate the diagnostic significance of structural changes in the anal sphincter (AS) in patients with complex rectal fistulas (CRF).Materials and Methods. This study analyzed the results of examination and surgical treatment of 87 patients with rectal fistulas. Following a comprehensive assessment, the structural changes in the anal sphincter (SCAS) among patients with complex rectal fistulas were classified into several categories. The first subgroup included 16 patients (18.4%) with complex rectal fistulas accompanied by inflammatory infiltration of the anal sphincter (reactive sphincteritis, RS). The second subgroup consisted of 24 patients (27.6%) who exhibited fibrotic changes in the anal sphincter (anal sphincter pectenosis, ASP). The third subgroup comprised 17 patients (19.5%) with complex rectal fistulas and defects (diastasis of AS muscles) in the anal sphincter fibers. The fourth subgroup served as the comparison group, consisting of 30 patients (34.5%) with complex rectal fistulas but without organic changes in the AS.Results and Discussion. The primary complaint among all patients with complex rectal fistulas was the presence of a fistula opening with purulent discharge, although additional symptoms varied depending on the type of structural changes in the AS. The study demonstrated that ultrasound showed a sensitivity of 87%, specificity of 69%, and overall accuracy of 92% in diagnosing rectal fistulas, consistent with data reported by other researchers. On ultrasound, reactive sphincteritis presented as a homogeneous or heterogeneous structure of anal sphincter fibers with varying shapes and sizes, characterized by hyperechogenicity intimately adjacent to fluid accumulations (or intersphincteric localization), filled with contents of varying degrees of echogenicity depending on the stage of inflammation. The ultrasound characteristics of anal sphincter pectenosis (ASP) differed from RS, showing a decrease in sphincter fiber volume and deformation of the AS with retraction of the muscular ring. Defects in the internal sphincter were characterized by varying degrees of hypoechogenicity, with lengths ranging from 0.3 to 1.2 cm, and were more frequently observed along the posterior rectal wall.Conclusions. Complex rectal fistulas are often associated with organic changes in the structure of the anal sphincter, manifesting as reactive sphincteritis, anal sphincter pectenosis, and defects in the muscle fibers of the external anal sphincter. The clinical course of the disease in patients with ASP is influenced by both the type of rectal fistula and the nature and severity of SCAS.

Long COVID in the UAE: symptomatology, gender gaps, and health implications among COVID-19 survivors

Abstract Background A growing number of COVID-19 survivors are experiencing symptoms post-SARS-CoV-2 infection, known as long COVID. It is a new multisystem condition and understanding its associated factors and its impact on individuals is crucial. This study aims to characterize long COVID in previously hospitalized patients in the UAE, identifying associated factors and assessing its impact on patients’ daily lives. Methods A multicenter retrospective cohort study was conducted in hospitals in Dubai and Sharjah from January 29, 2020 to October 14, 2021, involving RT-PCR confirmed cases. Clinical, epidemiologic, and long COVID data were collected via hospital records and phone interviews. Results Long COVID affected 48.7% of 533 patients, with 46.6% prevalence persisting over a year. A total of 43 symptoms across 11 organ systems were reported. Females had 1.83 times higher odds of long COVID (95% CI [1.22, 2.74], p = 0.003). Each additional initial symptom (AOR = 1.22, 95% CI [1.05, 1.40], p = 0.008), ICU admission (AOR = 1.77, 95% CI [1.06, 2.98], p = 0.030), and ≥ 2 comorbidities (AOR = 2.19, 95% CI [1.09, 4.40], p = 0.027) increased the odds of long COVID. Long COVID significantly impacted daily life, with poorer health ratings (AOR = 5.576, 95% CI [3.029, 10.265], p < .001), worse health status (AOR = 7.842, 95% CI [4.954, 12.415], p < .001), and work limitations due to physical (AOR = 4.808, 95% CI [3.229, 7.158], p < .001) and emotional issues (AOR = 3.149, 95% CI [2.01, 4.933], p < .001). This impact persisted beyond 12 months post-infection. Conclusions Long COVID presents prolonged multisystem involvement and substantial disability among survivors, necessitating further research to understand its lasting effects and intervention development to mitigate its impact Key messages • Long COVID poses a substantial challenge to public health in the UAE, affecting almost half of hospitalized survivors and extending its impact beyond 12 months post-infection. • Risk factors like gender initial symptoms, ICU stay, and comorbidities increase the risk of long COVID, warranting the need for tailored interventions and support strategies for vulnerable populations.

Genotype‒phenotype correlation in recessive DNAJB4 myopathy.

Protein aggregate myopathies can result from pathogenic variants in genes encoding protein chaperones. DNAJB4 is a cochaperone belonging to the heat shock protein-40 (HSP40) family and plays a vital role in cellular proteostasis. Recessive loss-of-function variants in DNAJB4 cause myopathy with early respiratory failure and spinal rigidity, presenting from infancy to adulthood. This study investigated the broader clinical and genetic spectrum of DNAJB4 myopathy. In this study, we performed whole-exome sequencing on seven patients with early respiratory failure of unknown genetic etiology. We identified five distinct pathogenic variants in DNAJB4 in five unrelated families of diverse ethnic backgrounds: three loss-of-function variants (c.547C > T, p.R183*; c.775C > T, p.R259*; an exon 2 deletion) and two missense variants (c.105G > C, p.K35N; c.181A > G, p.R61G). All patients were homozygous. Most affected individuals exhibited early respiratory failure, and patients from three families had rigid spine syndrome with axial weakness in proportion to appendicular weakness. Additional symptoms included dysphagia, ankle contractures, scoliosis, neck stiffness, and cardiac dysfunction. Notably, J-domain missense variants were associated with a more severe phenotype, including an earlier age of onset and a higher mortality rate, suggesting a strong genotype‒phenotype correlation. Consistent with a loss of function, the nonsense variants presented decreased stability. In contrast, the missense variants exhibited normal or increased stability but behaved as loss-of-function variants in yeast complementation and TDP-43 disaggregation assays. Our findings suggest that DNAJB4 is an emerging cause of myopathy with rigid spine syndrome of variable age of onset and severity. This diagnosis should be considered in individuals presenting with suggestive symptoms, particularly if they exhibit neck stiffness during infancy or experience respiratory failure in adults without significant limb muscle weakness. Missense variants in the J domain may predict a more severe phenotype.

The Antiviral and Antimalarial Prodrug Artemisinin from the Artemisia Species: A Review

Artemisinin is a truly fascinating drug in many ways. Since the unrestrained procedure of its detection, as an antimalarial drug, artemisinin has received a great deal of consideration. Recently, application of artemisinin-based combination therapy has been broadly applied for treating numerous ailments. Moreover, as an antimalarial compound, artemisinin and its associated compounds have abundant healing efficacy and can be repurposed for additional symptoms, like autoimmune infections, cancer, and viral contaminations. Recently a number of studies have highlighted the significance of the artemisinin-related compounds in SARS-CoV-2 treatment. The current review purposes to present a concise account of the history of the antiviral and antimalarial prodrugs—Artemisinin, from the Artemisia species. It is followed by its antiviral, antimalarial prospective, chemical nature and extraction procedure, photochemistry, mechanism of action, and its clinical trials and patents, and accentuates the significance of the mechanistic studies concerned for therapeutic results, both in viral and malarial circumstances.

Improving Diagnostic Yield in Patients with Pulsatile Tinnitus: A Ten-Year Analysis.

To determine the yield of a comprehensive diagnostic algorithm for patients with pulsatile tinnitus (PT) and to review the common etiologies and present clinical pears for their diagnosis. Retrospective chart review of patients with PT from 2013 to 2023. Charts were reviewed for demographic data (age, sex, BMI), side of PT (or bilateral), specialty clinic of initial evaluation, coexistent symptoms in addition to PT, and final diagnosis (or non-diagnosis). Clinical, audiometric, laboratory, and radiographic data were collected. Putative chart diagnoses were reviewed by the authors and deemed likely or unlikely to be the source of the patient's PT. Those with "unlikely" were grouped in the "idiopathic" cohort. The diagnostic algorithm is presented in detail. Two hundred and 90 patients were included for analysis. The overall diagnostic yield was 90.7% for all patients and 95.6% for those patients who completed the recommended workup - a substantial improvement over published rates. Twenty-nine etiologies were identified with the most common etiology was idiopathic intracranial hypertension (IIH). Twenty-one diagnoses comprised no more than 5% of patients. Seventy-three patients (25.2%) had more than one pathology as a potential source for their PT. PT can present a diagnostic challenge to the clinician. The findings of this study, however, reveal that proper evaluation based on obtaining a thorough history, performing a physical examination, coupled with properly directed imaging studies and blood testing can accomplish a high diagnostic yield of at least one potential etiology. 4 Laryngoscope, 2024.

Associations of diagnostic awareness with psychosocial symptoms and survival time in patients with advanced lung cancer.

Disclosing the diagnosis of lung cancer to patients is an issue, especially in the Middle East where cultural factors may prohibit disclosure from being done. The psychosocial consequences of diagnostic awareness and its impact on life expectancy of disclosure are an important issue that may influence this decision. The present study evaluated the effects of diagnostic awareness on psychosocial symptomatology and survival time in advanced lung cancer patients in Turkey. This prospective cohort study included 126 advanced lung cancer patients admitted to the oncology department between February 2021 and August 2021. A face-to-face survey included questions on age, gender, marital/employment statuses, comorbidities, and psychological symptoms (SCL-90-R). Diagnostic awareness was assessed by asking patients whether they knew their diagnosis. The correlation of diagnostic awareness with 2-year survival time was analyzed using Cox regression analysis. Of the 126 patients, 86 died at the time of follow-up. Survival time and scores on SCL-90-R symptom subscales were compared between diagnosis-aware (79.4%) and diagnosis-unaware groups (20.6%). Somatization (P = 0.04), depression (P = 0.01), hostility (P = 0.03), scores on additional symptom scales (P = 0.01), and Positive Symptom Total scores (P = 0.01) were significantly higher in the diagnosis-unaware group. No significant difference was found between diagnostic awareness and survival time (P = 0.24). Advanced lung cancer patients aware of their diagnosis experienced less psychosocial burden. However, no significant difference was found in survival time between diagnosis-aware and diagnosis-unaware patients. These findings suggest that the diagnosis should be disclosed to lung cancer patients after confirmation of diagnosis.

Genotype-phenotype correlation in recessive DNAJB4 myopathy.

Protein aggregate myopathies can result from pathogenic variants in genes encoding protein chaperones. DNAJB4 is a cochaperone belonging to the heat shock protein-40 (HSP40) family and plays a vital role in cellular proteostasis. Recessive loss-of-function variants in DNAJB4 cause myopathy with early respiratory failure and spinal rigidity, presenting from infancy to adulthood. This study investigated the broader clinical and genetic spectrum of DNAJB4 myopathy. In this study, we performed whole-exome sequencing on seven patients with early respiratory failure of unknown genetic etiology. We identified five distinct pathogenic variants in DNAJB4 in five unrelated families of diverse ethnic backgrounds: three loss-of-function variants (c.547C > T, p.R183*; c.775C > T, p.R259*; an exon 2 deletion) and two missense variants (c.105G > C, p.K35N; c.181A > G, p.R61G). All patients were homozygous. All affected individuals exhibited early respiratory failure, and patients from three families had rigid spine syndrome with axial weakness in proportion to appendicular weakness. Additional symptoms included dysphagia, ankle contractures, scoliosis, neck stiffness, and cardiac dysfunction. Notably, J-domain missense variants were associated with a more severe phenotype, including an earlier age of onset and a higher mortality rate, suggesting a strong genotype-phenotype correlation. Consistent with a loss of function, the nonsense variants presented decreased stability. In contrast, the missense variants exhibited normal or increased stability but behaved as loss-of-function variants in yeast complementation and TDP-43 disaggregation assays. Our findings suggest that DNAJB4 is an emerging cause of myopathy with rigid spine syndrome of variable age of onset and severity. This diagnosis should be considered in individuals presenting with suggestive symptoms, particularly if they exhibit neck stiffness during infancy or experience respiratory failure in adults without significant limb muscle weakness. Missense variants in the J-domain may predict a more severe phenotype.

Characterizing the Patterns of Cervical Cancer Symptom Recognition, Symptom Response, and Associated Factors Among Patients Treated in a Teaching Hospital in Ghana.

Cervical cancer is a major global health issue and ranks as the second leading cause of cancer-related deaths among women in Ghana. This study aimed to explore and characterize the patterns of symptom recognition associated with cervical cancer and the symptom responses among women in Ghana. A descriptive qualitative design utilizing 20 individual semistructured interview sessions was used. The study was conducted in one of Ghana's major cancer treatment centers. Data were collected using face-to-face interviews. The data were analyzed using NVivo 12 and presented as themes and subthemes. Data analysis revealed 2 main themes: barriers to symptom recognition and response and facilitators of early symptom recognition and symptom response. Barriers included deficient knowledge about cervical symptoms, spiritual attributions of symptoms, preference for herbal remedies for symptoms, misdiagnosis, and seeking help through multiple facility visits. Facilitating factors of symptom response include perceived severity/identification of additional symptoms, quick referrals with some navigation within the healthcare system, and advice from women's microcommunity. The study emphasizes the need for continuous educational efforts on cervical cancer and its symptoms. Healthcare providers, patients, and the public have a part to play in the awareness and early detection of cervical cancer. Initiatives that educate women about the early symptoms of cervical cancer and the importance of screening can help with early recognition. Educating communities about cervical cancer empowers individuals to take charge of their health and encourages supportive environments for women to seek care.

Polysomnographic and clinical characteristics of sleep apnea headache patients.

Sleep apnea headache can be defined as a persistent, widespread, throbbing headache that occurs recurrently, is not accompanied by any additional symptoms after waking up, and usually resolves within four hours. Diagnosis of the condition requires confirmation through polysomnography with an apnea-hypopnea index of at least 5, indicating the presence of obstructive sleep apnea syndrome (OSAS). While sleep apnea headaches are common in 10-15% of individuals with OSAS, morning headaches are experienced by 5% of this population. The aim of this study is to examine both polysomnographic and clinical features associated with sleep apnea headache in individuals confirmed to have OSAS by polysomnography. The study was conducted in the sleep center of University of Health Science, Erenköy Mental and Nervous Disease Training and Research Hospital. We have examined the clinical and polysomnographic data of the patients with sleep apnea headache (SAH) diagnosed according to IHS-3 criteria retrospectively and grouped the patients as mild, moderate and severe OSAS. Patients with morning headache except sleep apnea headache and under PAP titration treatment were excluded. The differences between the sleep macro structures of patients with (WSAH) and without sleep apnea headache (WOSAH) were examined. The WSAH group consisted of 384 participants and the control group (WOSAH) consisted of 294 participants The mean age was 46.29 ± 12.18 and 45.08 ± 12.62 years, respectively. Patients in the WSAH group had significantly higher scores on the Epworth Sleepiness Scale (ESS) (p = 0.004) and higher periodic limb movement index (PLMI) (p = 0.014) compared to the WOSAH group. WSAH patients exhibited shorter wake times after sleep onset (WASO) and lower scores on the sleep quality index, in contrast to WOSAH patients. Additionally, within the WSAH group, there was a negative correlation between age and several sleep parameters, including total sleep parameters. A positive correlation was observed between sleep duration (p = 0.009), waking up after sleep (p = 0.043), sleep efficiency (p = 0.001) and apnea-hypopnea index (AHI) (p = 0.018). Additionally, ESS scores were positively correlated with AHI and total awake time (p = 0.000 and p = 0.008, respectively), while negatively correlated with stage N3 sleep percentage and mean minimum oxygen level (p = 0.001 and p = 0.020, respectively) in the WSAH group. The causes and possible mechanisms of sleep apnea headache are not fully clarified and the underlying processes are not fully understood. Sleep apnea headaches appear to be related to disturbances in nocturnal sleep. Dysregulation in regions that modulate sleep and nociception may be one possible mechanism.

Cardiometabolic Morbidity (Obesity and Hypertension) in PTSD: A Preliminary Investigation of the Validity of Two Structures of the Impact of Event Scale-Revised.

Background: Posttraumatic stress disorder (PTSD) and/or specific PTSD symptoms may evoke maladaptive behaviors (e.g., compulsive buying, disordered eating, and an unhealthy lifestyle), resulting in adverse cardiometabolic events (e.g., hypertension and obesity), which may implicate the treatment of this complex condition. The diagnostic criteria for PTSD have lately expanded beyond the three common symptoms (intrusion, avoidance, and hyperarousal). Including additional symptoms such as emotional numbing, sleep disturbance, and irritability strengthens the representation of the Impact of Event Scale-Revised (IES-R), suggesting that models with four, five, or six dimensions better capture its structure compared to the original three-dimensional model. Methods: Using a convenience sample of 58 Russian dental healthcare workers (HCWs: mean age = 44.1 ± 12.2 years, 82.8% females), this instrumental study examined the convergent, concurrent, and criterion validity of two IES-R structures: IES-R3 and IES-R6. Results: Exploratory factor analysis uncovered five factors, which explained 76.0% of the variance in the IES-R. Subscales of the IES-R3 and the IES-R6 expressed good internal consistency (coefficient alpha range = 0.69-0.88), high convergent validity (item total correlations r range = 0.39-0.81, and correlations with the IES-R's total score r range = 0.62-0.92), excellent concurrent validity through strong correlations with the PTSD Symptom Scale-Self Report (PSS-SR: r range = 0.42-0.69), while their criterion validity was indicated by moderate-to-low correlations with high body mass index (BMI: r range = 0.12-0.39) and the diagnosis of hypertension (r range = 0.12-0.30). In the receiver-operating characteristic (ROC) curve analysis, all IES-R models were perfectly associated with the PSS-SR (all areas under the curve (AUCs) > 0.9, p values < 0.001). The IES-R, both hyperarousal subscales, and the IES-R3 intrusion subscale were significantly associated with high BMI. Both avoidance subscales and the IES-R3 intrusion subscale, not the IES-R, were significantly associated with hypertension. In the two-step cluster analysis, five sets of all trauma variables (IES-R3/IES-R6, PSS-SR) classified the participants into two clusters according to their BMI (normal weight/low BMI vs. overweight/obese). Meanwhile, only the IES-R, PSS-SR, and IES-R3 dimensions successfully classified participants as having either normal blood pressure or hypertension. Participants in the overweight/obese and hypertensive clusters displayed considerably higher levels of most trauma symptoms. Input variables with the highest predictor importance in the cluster analysis were those variables expressing significant associations in correlations and ROC analyses. However, neither IES-R3 nor IES-R6 contributed to BMI or hypertension either directly or indirectly in the path analysis. Meanwhile, age significantly predicted both health conditions and current smoking. Irritability and numbing were the only IES-R dimensions that significantly contributed to current smoking. Conclusions: The findings emphasize the need for assessing the way through which various PTSD symptoms may implicate cardiometabolic dysfunctions and their risk factors (e.g., smoking and the intake of unhealthy foods) as well as the application of targeted dietary and exercise interventions to lower physical morbidity in PTSD patients. However, the internal and external validity of our tests may be questionable due to the low power of our sample size. Replicating the study in larger samples, which comprise different physical and mental conditions from heterogenous cultural contexts, is pivotal to validate the results (e.g., in specific groups, such as those with confirmed traumatic exposure and comorbid mood dysfunction).

Quick action required: revealing pheochromocytoma as the hidden trigger behind postoperative hypertensive crisis.

Managing patients who present with elevated blood pressure (BP) requires careful but expeditious assessment and triage to differentiate between those at immediate risk of complications and those for whom BP elevation does not pose an immediate threat to health. We present a case of a 54-year-old healthy male patient who experienced refractory hypertension during the immediate postoperative period following nasal surgery. Additional gastrointestinal symptoms and imaging findings made it possible to consider a catecholamine-producing tumour as the primary cause. Despite efforts, managing hypertension continued to be a challenge, and major neurologic complications arose within the following hours. This case illustrates the potential for rapid changes in the clinical scene during hypertensive emergency management. If not addressed promptly, a routine postoperative complication (at first glance) can turn into serious complications, particularly when there are uncommon underlying causes involved.

A Novel De Novo Gain-of-Function CACNA1D Variant in Neurodevelopmental Disease With Congenital Tremor, Seizures, and Hypotonia.

De novo gain-of-function variants in the CACNA1D gene, encoding the L-type voltage-gated Ca2+ channel CaV1.3, cause a multifaceted syndrome. Patients show variable degrees of autism spectrum disorder, developmental delay, epilepsy, and other neurologic and endocrine abnormalities (primary aldosteronism and/or hyperinsulinemic hypoglycemia). We study here a novel variant [c.3506G>A, NM_000720.4, p.(G1169D)] in 2 children with the same CACNA1D mutation but different disease severity. The clinical data of the study patients were collected. After molecular analysis and cloning by site-directed mutagenesis, patch-clamp recordings of transfected tsA201 cells were conducted in whole-cell configuration. The functional effects of wild-type and mutated channels were analyzed. One child is a severely affected boy with a novel de novo CACNA1D variant with additional clinical symptoms including prenatal-onset tremor, congenital respiratory insufficiency requiring continuous positive airway pressure ventilation, and sensorineural deafness. Despite episodes of hypoglycemia, insulin levels were normal. Aldosterone:renin ratios as a screening parameter for primary aldosteronism were variable. In the second patient, putative mosaicism of the p.(G1169D) variant was associated with a less severe phenotype. Patch-clamp electrophysiology of the p.(G1169D) variant in a heterologous expression system revealed pronounced activity-enhancing gating changes, including a shift of channel activation and inactivation to more hyperpolarized potentials, as well as impaired channel inactivation and deactivation. Despite retained sensitivity to the Ca2+ channel blocker isradipine in vitro, no beneficial effects of isradipine or nifedipine treatment were observed in the index case. Through this report, we expand the knowledge about the disease presentation in patients with CACNA1D variants and show the novel variant's modulatory effects on CaV1.3 gating.

Complex Posttraumatic Stress Disorder (CPTSD) is Uniquely Linked to Suicidality Beyond Posttraumatic Stress Disorder (PTSD) in Adults with Childhood Maltreatment: A Multinational Study Across Four Countries

BackgroundSuicide is a leading cause of death worldwide, with childhood maltreatment identified as a significant risk factor for suicidal behavior in adulthood. The link between childhood maltreatment and suicidality is well-documented; however, the role of complex posttraumatic stress disorder (CPTSD), which includes an additional symptom cluster of disturbances in self-organization (DSO) compared to posttraumatic stress disorder (PTSD), remains underexplored. This study aimed to investigate the association between meeting the criteria for ICD-11 PTSD or CPTSD and suicidality in adults with a history of childhood maltreatment across culturally diverse samples. MethodsData were collected across four sites: the United States, the United Kingdom, China, and Malaysia. The Childhood Trauma Questionnaire (CTQ), Suicidal Behaviors Questionnaire-Revised (SBQ-R), and International Trauma Questionnaire (ITQ) were used to assess childhood maltreatment, suicidality, and PTSD or CPTSD, respectively. Linear regressions were conducted to examine the associations, controlling for demographic variables (age, sex, ethnicity, educational level, and subjective socioeconomic status) as well as the severity of maltreatment (CTQ total scores). ResultsAmong the 1,324 participants who experienced childhood maltreatment, meeting the criteria for CPTSD was significantly associated with higher suicidality compared to not meeting the criteria for either PTSD or CPTSD (B(SE) = 1.68 (0.30), p < .001), or only meeting the criteria for PTSD (B(SE) = 1.38 (0.43), p < .001). In contrast, meeting the criteria for PTSD alone was not significantly associated with suicidality (B(SE) = 0.35 (0.46), p = .45). These associations remained consistent across different cultural settings. ConclusionThe study findings highlight the unique association of CPTSD with suicidality in adults with a history of childhood maltreatment, suggesting that the DSO symptom cluster of CPTSD, which distinguish it from PTSD, play a critical role in the development of suicidality in this population. Targeting these symptoms may be essential for effective intervention strategies. Screening for childhood maltreatment and CPTSD in individuals at risk of suicide is crucial for guiding treatment planning.