Unique Clinical Presentation Research Articles

A genotypic and phenotypic analysis of four unrelated Chinese patients with Pitt–Hopkins syndrome

BackgroundPitt–Hopkins syndrome (PTHS) is a rare genetic condition caused by a mutation in the transcription Factor 4 (TCF4) gene and characterized by its unique clinical presentations. At present, there is an incomplete understanding of the possible TCF4 mutations and their downstream consequences, and no reliable treatment exists for patients with PTHS. Elucidating the variations in TCF4 occurring in PTHS could lead to new treatment ideas.Case presentationWe described the clinical and genetic characteristics of four Chinese patients with PTHS. Genetic mutations related to central nervous system (CNS) disorders were identified via high-throughput sequencing. The patient’s mutations were subsequently confirmed with Sanger sequencing. Most patients had facial features typical of PTHS; however, Patient 2 demonstrated poor auricle shape. Each patient presented with differing levels of delayed development and intellectual impairment. The patients showed a splice site mutation in intron 15 of TCF4 (c.1452 + 3A > G), a frameshift mutation in exon 18 of TCF4 (c.1942delA), and two missense mutations in exon 19 of TCF4 (c. 2147C > T and c.2026A > G).ConclusionsWe discovered four new TCF4 mutations in Chinese children with PTHS. To our knowledge, the c.2026A > G and c.1942delA mutations have not yet been reported. The detection of these mutations can help accurately diagnose PTHS early, especially in patients whose clinical symptoms are not obvious. Exploring the genotype and phenotype of individuals with PTHS, will enrich our understanding and guide further research into the role of TCH4.

A familial subtype of gambling disorder.

Although family history of psychiatric disorders has often been considered potentially useful in understanding clinical presentations in patients, it is less clear what a positive gambling family history means for people with gambling disorder. We sought to understand the clinical impact of having a first-degree relative with gambling disorder in a sample of adults with gambling disorder. Data from 455 participants (aged 18-65 years) who had participated in previous pharmacological and psychotherapeutic clinical trials for gambling disorder were pooled in a secondary analysis. Demographic and clinical variables were compared between those who did versus did not have one or more first-degree relative(s) with gambling disorder. Additionally, we examined whether a family history of gambling disorder was associated with treatment outcome. 223 (49.0%) participants had at least one first-degree family member(s) with gambling disorder. In terms of clinical variables, family history of gambling disorder was significantly associated with being female, having an earlier age of gambling onset, longer duration of untreated gambling illness, a greater likelihood of developing legal problems secondary to gambling, and higher rates of alcohol use disorder in family members. Family history of gambling disorder was also associated with a greater gambling symptom improvement frompharmacotherapy. These results indicate that gamblers with a first-degree family member with a gambling disorder may have a unique clinical presentation and better response to treatment interventions.

Allergic contact dermatitis of the scalp: a review of an underdiagnosed entity.

It is hypothesized that scalp allergic contact dermatitis (ACD) in women is commonly mistaken for other disorders due to overlapping symptoms and unique clinical presentations. This study reviews the potential underdiagnosis and misdiagnosis of scalp ACD and explores ways to improve diagnostic accuracy. This study conducted an extensive literature review to identify diagnostic challenges, common misdiagnoses, and diagnostic approaches for scalp ACD, focusing on standard versus targeted patch testing techniques. Scalp ACD, often misdiagnosed as seborrheic dermatitis due to similar symptoms, has atypical presentations such as hair thinning, hair loss, and erythematous lesions affecting neighboring regions. Trichoscopy can help distinguish scalp ACD, identifying its patchy distribution of thin white scales, in contrast to the yellow scaling of seborrheic dermatitis. Standardized patch testing further contributes to diagnostic errors, with a study reporting 83% of patients who tested negative with standardized patch tests were positive when using their personal products. Individualized patch testing is more effective in identifying causative allergens and accurately diagnosing scalp ACD. It is a retrospective review. Several factors contribute to scalp ACD's misdiagnosis for conditions such as seborrheic dermatitis. The significant discrepancy in ACD detection rates between personalized and standardized patch tests in women emphasizes the importance of using patient-specific products in diagnostic testing. Incorporating scalp ACD more readily into one's differential, employing individualized patch testing with trichoscopy, and accounting for neighboring symptomatic areas are all crucial elements in improving diagnostic accuracy for scalp ACD in women.

“The silent killer”: a case series on pulmonary embolisms

Background and objectives. Pulmonary embolism (PE) is the third most common cause of death among hospitalized patients. The clinical presentation of a PE is highly variable and requires a high degree of suspicion to diagnose especially in a timely manner. A good grasp of various risk factors that may predispose a patient to a venous thromboembolism (VTE) and knowledge of the various presentations possible is required in order to diagnose and initiate potentially life-saving treatment in these patients. Here, we will look at five unique clinical presentations of a PE that highlight the variability of presentation in these cases. Materials and methods. 5 unique clinical presentations of pulmonary embolism were chosen and clinical data discussed. These cases included male and female patients of different age groups, with different risk factors and drastically different clinical presentations. The cases chosen ranged from a young male in his 20s with no risk factors presenting to us with an episode of syncope to a 62 year old diabetic female who presented with a stroke. Their different presentations, our approach to the diagnostic process and their subsequent management were emphasized. Conclusions. The spectrum of clinical presentation in a case of pulmonary embolism is very wide. A high degree of clinical suspicion is necessary to make a timely diagnosis of a PE, especially in the ER. This is especially pertinent given the fact that mortality in untreated cases is a whopping 30% compared to 8% with timely therapy. Thus it is imperative for clinicians to have a comprehensive understanding of the various presentations possible, to allow timely detection and prevent delays in the potentially lifesaving therapy that must be initiated.

Immunohistopathological analyses of a case of pemphigus vegetans with antibodies against desmoglein 1 and desmocollins 1-3.

Pemphigus vegetans is a rare type of pemphigus characterized by vegetative lesions primarily localized to the intertriginous area. Despite its unique clinical presentation, the underlying pathomechanism remains unclear owing to the rarity of the disease. We report a case of pemphigus vegetans with antibodies against desmoglein 1 and desmocollins 1-3. Furthermore, immunohistochemical analyses were performed to address the pathogenesis of this disease. A 73-year-old man presented with multiple vegetative plaques with erythema on the trunk, groins, and extremities. Mucosal lesions were not observed. Laboratory examinations revealed mild leukocytosis with eosinophilia. A histopathological examination of the skin lesion showed epidermal hyperplasia and intraepidermal abscesses with marked infiltration of neutrophils and eosinophils, and infiltration of lymphocytes and eosinophils into the upper derms. Bacterial culture of the skin tissue was positive for Staphylococcus aureus. Direct immunofluorescence showed deposits of IgG and C3 on keratinocyte surfaces in the epidermis. Autoantibodies against desmoglein 1 and autoantibodies against desmocollin 1, desmocollin 2, and desmocollin 3 were detected by enzyme-linked immunosorbent assays. The diagnosis of pemphigus vegetans was made. Initiation of prednisolone (1.0 mg/kg/day) gradually improved his skin symptoms. We performed immunohistochemical analyses of the lesional skin, which revealed infiltration of CD3-positive, CD4-positive, and CD68-positive cells in the upper dermis, but CD20- or CD56-positive cells were negative. In addition, the present case showed more prominent infiltration of IL-17A- and IL-22-positive cells in the upper dermis than in pemphigus foliaceus, a type of pemphigus with autoantibodies against desmoglein 1. Furthermore, these cells co-expressed CD3 and CD68. We hypothesized that IL-22 and IL-17A produced by T cells and macrophages and their dysregulation might be involved in the pathogenesis of pemphigus vegetans. Additionally, skin colonization and/or infection with Staphylococcus aureus could potentially contribute to the pathogenesis of the disease.

International survey on invasive lobular breast cancer identifies priority research questions

There is growing awareness of the unique etiology, biology, and clinical presentation of invasive lobular breast cancer (ILC), but additional research is needed to ensure translation of findings into management and treatment guidelines. We conducted a survey with input from breast cancer physicians, laboratory-based researchers, and patients to analyze the current understanding of ILC, and identify consensus research questions. 1774 participants from 66 countries respondents self-identified as clinicians (N = 413), researchers (N = 376), and breast cancer patients and advocates (N = 1120), with some belonging to more than one category. The majority of physicians reported being very/extremely (41%) to moderately (42%) confident in describing the differences between ILC and invasive breast cancer of no special type (NST). Knowledge of histology was seen as important (73%) and as affecting treatment decisions (51%), and most agreed that refining treatment guidelines would be valuable (76%). 85% of clinicians have never powered a clinical trial to allow subset analysis for histological subtypes, but the majority would consider it, and would participate in an ILC clinical trials consortium. The majority of laboratory researchers, reported being and very/extremely (48%) to moderately (29%) confident in describing differences between ILC and NST. They reported that ILCs are inadequately presented in large genomic data sets, and that ILC models are insufficient. The majority have adequate access to tissue or blood from patients with ILC. The majority of patients and advocates (52%) thought that their health care providers did not sufficiently explain the unique features of ILC. They identified improvement of ILC screening/early detection, and identification of better imaging tools as top research priorities. In contrast, both researchers and clinicians identified understanding of endocrine resistance and identifying novel drugs that can be tested in clinical trials as top research priority. In summary, we have gathered information from an international community of physicians, researchers, and patients/advocates that we expect will lay the foundation for a community-informed collaborative research agenda, with the goal of improving management and personalizing treatment for patients with ILC.

Management of metastatic pheochromocytomas and paragangliomas: when and what

Recently, the treatment landscape for metastatic pheochromocytomas and paragangliomas (MPPGL) has seen both progress and setbacks. We provide an up-to-date review of the multimodality management of MPPGL and discuss novel opportunities and current challenges in the treatment landscape. Given the unique clinical presentation of MPPGL, we discuss the management of hormone-related clinical sequelae and traditional modalities of therapy. Advances in the understanding of the molecular biology of these diverse tumors have enabled novel strategies such as augmenting DNA damage by targeted delivery of radionuclides such as 131I and 177Lu, abrogating tumor angiogenesis, hypoxia resistance, and DNA damage repair. Despite progress, we address the significant challenges still faced by patients and researchers engaged in efforts to improve outcomes in these rare cancers.

TABES DORSALIS: IS THE DIAGNOSIS A CHALLENGE NOWADAYS?

Purpose: To present a rare case of neurosyphilis, the tertiary form of syphilitic infection, following adequate but belated treatment and manifesting with a variety of clinical signs and further progression to tabetic neurosyphilis. Known as the "great imitator", neurosyphilis is often misdiagnosed and underestimated. Materials/methods: A 48-year-old male patient was admitted to the Neurology clinic of UMHAT "Dr Georgi Stranski" Pleven, Bulgaria, with progressive neurological deficit including numbness in the lower limbs, imbalance and wide-based gait. The T2W- MRI showed abnormally high longitudinal signals at Th12-L1 level, consistent with transverse myelitis. CSF analysis revealed leucocytic pleocytosis, elevated proteins and normal glucose. The nerve conduction studies confirmed sensory motor polyneuropathy. Results: After treatment with intravenous aqueous crystalline (IV) penicillin, 2 million intravenously every 4 hours for 20 days, the sensory symptoms reduced. The coordination disturbances persisted, but the gate showed moderate improvement. Conclusions: The diagnosis of syphilitic myelitis, known as tabes dorsalis, is always complex, not only because of its rarity but because of its unique clinical presentation with multiple clinical symptoms, mimicking other more common neurological disorders. Though confirmation of the diagnosis needs a lot of laboratory and neuroimaging studies, the option of effective specific treatment is worth all the efforts.

An unique clinical presentation of choledochal cyst in middle aged female

An unique clinical presentation of choledochal cyst in middle aged female

Genetic Rearrangements in Different Salivary Gland Tumors: A Systematic Review.

Salivary gland tumors (SGT) encompass a wide range of neoplasms, each with its own unique histological type and clinical presentation. This review hones in on prevalent subtypes of SGTs, including adenoid cystic carcinoma (ACC), salivary duct carcinoma (SDC), and polymorphous adenocarcinoma (PAC). The articles, identified through specific keywords, were meticulously screened in databases like PubMed, Scopus, Google Scholar, and Web of Science from 2018 to 2023. Eight articles delved into genetic modifications among the selected SGT types. A fusion protein known asMYB-NF1B is typically associated with ACC, promoting cell proliferation while inhibiting apoptosis. The presence of MYB modifications in ACCs is a beacon of hope, as it is linked to a more favorable prognosis. In contrast, SDCs often exhibit HER2 expression. The invasive nature of SGTs contributes to their resistance to treatment. In the case of PAC, the role of PRKD1 is particularly noteworthy. PRKD1, integrated with other genes from the PRKD1/2/3 cluster, helps to differentiate PAC from other diseases. Furthermore, the genetic profiles of KTN1-PRKD1) and PPP2R2A:PRKD1 are distinct. The significant genetic variability among SGTs necessitates meticulous examination. This field is in a constant state of evolution, with new discoveries reshaping our understanding. Genetics is a key player in deciphering SGTs and tailoring treatments. This complex neoplasm demands ongoing research to uncover all genetic influences, thereby enhancing diagnostic methodologies, therapeutic strategies, and patient outcomes.

Comparative Pathogenesis of Two Lineages of Powassan Virus Reveals Distinct Clinical Outcome, Neuropathology, and Inflammation.

Tick-borne flaviviruses (TBFV) can cause severe neuroinvasive disease which may result in death or long-term neurological deficit in over 50% of survivors. Multiple mechanisms for invasion of the central nervous system (CNS) by flaviviruses have been proposed including axonal transport, transcytosis, endothelial infection, and Trojan horse routes. Flaviviruses may utilize different or multiple mechanisms of neuroinvasion depending on the specific virus, infection site, and host variability. In this work we have shown that the infection of BALB/cJ mice with either Powassan virus lineage I (Powassan virus) or lineage II (deer tick virus) results in distinct spatial tropism of infection in the CNS which correlates with unique clinical presentations for each lineage. Comparative transcriptomics of infected brains demonstrates the activation of different immune pathways and downstream host responses. Ultimately, the comparative pathology and transcriptomics are congruent with different clinical signs in a murine model. These results suggest that the different disease presentations occur in clinical cases due to the inherent differences in the two lineages of Powassan virus.

Comparison of Patterns and Demographics of Isolated Traumatic Mandibular Fracture Between Incarcerated and General Populations.

Introduction The management of maxillofacial trauma can be challenging in different unique clinical presentations. While maxillofacial fractures vary in location based on the mechanism of injury, the mandibular fracture is noted to be one of the most common facial fractures. The objective of this study was to explore the differences in injury patterns, outcomes, and demographics of isolated traumatic mandibular fractures between incarcerated and general populations. Methods This retrospective study analyzed consecutive patients presenting for trauma care from January 1, 2010, to December 31, 2020, at the Arrowhead Regional Medical Center (ARMC).Patients 18 years and older were included in this study. Patients diagnosed with mandibular fracture as the primary diagnosis at admission and discharge were identified using the International Classification of Disease, Ninth and Tenth Revision (ICD-9, ICD-10) Code. Patient demographics were extracted from their electronic medical records and included race, marital status, and insurance status. Results A total of 1080 patients with confirmed mandibular fractures were included in the final analysis. Among these patients, 87.5% (n=945) were males, 40% (n=432) of the patients were Hispanic, and the average age was 31.55 years old. The most common mechanism of injury was blunt trauma secondary to assault. Compared to the general population with mandibular fracture, the incarcerated patients with mandibular fracture were more likely to be males (96.1% vs 86.1% for incarcerated population vs. general population respectively, p=0.0005). No other variables were statistically different between these two groups. Conclusion The evidence from this study suggests that the patterns, outcomes, and demographicsof mandibular fracture in both incarcerated and general populations are similar.

Abstract PO1-14-10: Comprehensive clinicogenomic characterization of inflammatory breast cancer

Abstract BACKGROUND: Inflammatory breast cancer (IBC) is a rare type of breast cancer associated with a unique clinical presentation and overall poor outcomes, recognized as a distinct category by the AJCC staging system. The biological mechanisms driving the IBC phenotype are relatively undefined—partially due to a lack of comprehensive, large-scale genomic studies and limited clinical cohorts. Here, we report one of the largest, subtype-informed clinicogenomic characterizations of IBC to date. METHODS: A retrospective analysis of 2457 patients with metastatic breast cancer who underwent targeted tumor-only DNA-sequencing (OncoPanel, up to 447 cancer-associated genes) was performed at Dana-Farber Cancer Institute. Clinicopathologic, single nucleotide variant (SNV), copy number variant (CNV) and tumor mutational burden (TMB) comparisons were made between IBC and non-IBC cases. Median follow-up was 28.1 months. RESULTS: Our profiled cohort included 140 patients with IBC specimens (n = 68 primary tumors, 72 metastatic tumors) and 2317 patients with non-IBC specimens (n = 702 primaries, 65 local recurrences, 1550 metastases). Of these, 87.4% of patients were White, 4.7% Black, 3.6% Asian or Pacific Islander, and 4.3% other/unknown. Clinicopathologic differences between IBC and non-IBC cases were consistent with previous reports—including younger age at diagnosis of metastatic disease (51 vs 54 years, p = 0.04), and a higher proportion of grade 3, estrogen receptor-negative and HER2-positive tumors (p < 0.001). Among the hormone-receptor (HR)-positive subtype, IBC tumors showed a significant enrichment in Luminal B (LumB)-inferred disease (62.5% vs 39.8%, p < 0.005), defined as tumors with grade 3 or progesterone receptor staining < 10%. The most recurrent somatic alterations spanning all subtypes in IBC were TP53 (72%), ERBB2 (32%), PIK3CA (24%), CCND1 (12%), MYC (9%), FGFR1 (8%) and GATA3 (8%). A multivariate logistic regression analysis accounting for HR and HER2 status revealed a significant enrichment in TP53 SNVs in IBC vs non-IBC (OR 2.08 [95% CI 1.34-3.24], adjusted p-value 0.04). Frequency of TP53 alterations in IBC vs non-IBC cases was 85.1% vs 64.3% in HER2-positive and 50.0% vs 27.7% in HR-positive disease—with an enrichment of TP53 mutations in IBC LumB-inferred tumors vs non-LumB (64% vs 26%, p < 0.05). When comparing HR+ IBC LumB vs HR+ non-IBC LumB cases, TP53 mutations were again enriched (p < 0.05)—suggesting LumB-like histopathology is not the only driving feature of TP53 enrichment in HR+ IBC. TMB did not differ substantially between IBC and non-IBC and no other statistically significant enrichments were observed, including when grouping mutations into six canonical cancer pathways (cell cycle, Notch signaling, PI3K pathway, RTK/RAS signaling, TP53 pathway and WNT signaling). CONCLUSIONS: Taken together, this study provides a comprehensive landscape of somatic alterations in a large cohort of patients with metastatic IBC and non-IBC. Our data support a lack of major genomic differences other than enrichments in TP53 mutations and an associated LumB-like histopathology. These results both reinforce the importance of TP53 mutations in IBC biology and suggest additional analyses beyond somatic DNA-level changes are warranted. Future efforts with the DFCI IBC cohort will assess germline-somatic interactions, non-genomic or transcriptomic characterizations, and potential environmental influences to better understand the mechanisms driving this unique disease. Citation Format: Nolan Priedigkeit, Beth Harrison, Melissa Hughes, Robert Shue, Yvonne Li, Gregory Kirkner, Claire Remolano, Sarah Strauss, Janet Files, Anne-Marie Feeney, Ayesha Mohammed-Abreu, Ana Garrido-Castro, Romualdo Barroso-Sousa, Brittany Bychkovsky, Faina Nakhlis, Jennifer Bellon, Tari King, Bruce Johnson, Lynette Sholl, Deborah Dillon, Beth Overmoyer, Sara Tolaney, Andrew Cherniack, Nancy Lin, Filipa Lynce. Comprehensive clinicogenomic characterization of inflammatory breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-14-10.

Clinical profiles of adolescent personality pathology: a latent structure examination of the Semi-Structured Interview for Personality Functioning DSM-5 (STiP-5.1) in a help-seeking sample

BackgroundDespite the introduction of dimensional conceptualisations of personality functioning in the latest classification systems, such as Criterion A of the Alternative Model of Personality Disorders in the DSM-5, heterogeneous clinical presentation of personality pathology remains a challenge. Relatedly, the latent structure of personality pathology as assessed by the Semi-Structured Interview for Personality Functioning DSM-5 (STiP-5.1) has not yet been comprehensively examined in adolescents. Therefore, this study aimed to examine the latent structure of the STiP-5.1, and, based on those findings, to describe any unique clinical profiles that might emerge.MethodsThe final sample comprised 502 participants aged 11–18 years consecutively recruited from a specialised personality disorder outpatient service, as well as general day clinic and inpatient wards at the University Hospital University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University Hospital Bern, Switzerland. Participants were assessed using the STiP-5.1, as well as a battery of other psychological measures by clinical psychologists or trained doctoral students. Variations of Factor Analysis, Latent Class Analysis and Factor Mixture Models (FMM) were applied to the STiP-5.1 to determine the most appropriate structure.ResultsThe best fitting model was an FMM comprising four-classes and two factors (corresponding to self- and interpersonal-functioning). The classes differed in both overall severity of personality functioning impairment, and in their scores and clinical relevance on each element of the STiP-5.1. When compared to the overall sample, classes differed in their unique clinical presentation: class 1 had low impairment, class 2 had impairments primarily in self-functioning with high depressivity, class 3 had mixed levels of impairment with emerging problems in identity and empathy, and class 4 had severe overall personality functioning impairment.ConclusionsA complex model incorporating both dimensional and categorical components most adequately describes the latent structure of the STiP-5.1 in our adolescent sample. We conclude that Criterion A provides clinically useful information beyond severity (as a dimensional continuum) alone, and that the hybrid model found for personality functioning in our sample warrants further attention. Findings can help to parse out clinical heterogeneity in personality pathology in adolescents, and help to inform early identification and intervention efforts.

West Nile Virus Meningoencephalitis—A Consideration for Earlier Investigation

West Nile Virus (WNV) is an arbovirus endemic to many countries and has caused over 56,000 cases, with 2776 deaths in the U.S. from 1999 to 2022. WNV occurs most often in the fall, typically affecting elderly populations in states like Nebraska and Arizona. Currently, supportive care is the only management for WNV. Our case is a female patient in her mid-70s in an intermountain state who presented in the fall with WNV meningoencephalitis and experienced a delay in care due to the unique clinical presentation. This demonstrates the importance of early inclusion of WNV in the differential for altered mental status, especially with WNV risk factors, and expedition of supportive care. Doing so could potentially reduce antibiotic duration and hospital costs.

CLINICAL PROFILE OF PERIPHERAL NEUROPATHY IN GERIATRIC POPULATION

Objectives: The objective of this study was to describe the clinical profile of peripheral neuropathy (PN) in the geriatric population. Methods: This prospective observational study was done among patients >65 years, found to have PN by Neuropathy Symptom Score, who were undergone history and clinical examination at the Department of Medicine and Gandhi Medical College and associated Hamidia Hospital Bhopal. Nerve conduction study was done in all subjects to observe the pattern and type of various peripheral neuropathies. Special investigations such as Serum Vitamin B-12, toxin screening of lead and arsenic, viral serology using the ELISA method, serum and urine electrophoresis, rheumatoid factor, antinuclear antibodies (ANA), and antinuclear cytoplasmic antibodies (c-ANCA and p-ANCA), and CSF examination were done as and when needed. Results: Most of the patients were in the 60–65 years [93 (46.5%)] of age followed by 66–70 years [54 (27%)]. Most common clinical feature was Tingling [120 (60%)] followed by Tingling and Numbness [36 (18%)]. In most of the subjects, deep tendon reflexes were normal [132 (66%)] whereas in 42 (21%) subjects deep tendon reflexes were impaired and in 26 (13%) subjects deep tendon reflexes were absent. Most of the patients had sensory motor axonal demyelinating neuropathy [8 (4%)]. Conclusion: PN is a heterogeneous disease with diverse pathology. Recognition of the clinical homolog of these pathological processes is the first step in achieving the appropriate form of intervention. Treatment should be individualized such that the particular manifestation and underlying pathogenesis of each patient’s unique clinical presentation are considered.

Differential Diagnosis of "Foot Drop": Implications for Peripheral Nerve Surgery.

At least 128,000 patients in the United States each year suffer from foot drop. This is a debilitating condition, marked by the inability to dorsiflex and/or evert the affected ankle. Such patients are rendered to a lifetime of relying on an ankle-foot orthosis (AFO) for walking and nighttime to prevent an equinovarus contracture. This narrative review explores the differential diagnosis of foot drop, with a particular focus on clinical presentation and recovery, whether spontaneously or through surgery. Contrary to popular belief, foot drop can be caused by more than just insult to the common peroneal nerve at the fibular head (fibular tunnel). It is a common endpoint for a diverse spectrum of nerve injuries, which may explain its relatively high prevalence. From proximal to distal, these conditions include lumbar spine nerve root damage, sciatic nerve palsy at the sciatic notch, and common peroneal nerve injury at the fibular head. Each nerve condition is marked by a unique clinical presentation, frequency, likelihood for spontaneous recovery, and cadre of peripheral nerve techniques. The ideal surgical technique for treating foot drop, other than neurolysis for compression, remains elusive as traditional peripheral nerve procedures have been marred by a wide spectrum of functional results. Based on a careful understanding of why past techniques have achieved limited success, we can formulate a working set of principles to help guide surgical innovation moving forward, such as fascicular nerve transfer.

Identifying clinical phenotypes of frontotemporal dementia in post-9/11 era veterans using natural language processing.

Frontotemporal dementia (FTD) encompasses a clinically and pathologically diverse group of neurodegenerative disorders, yet little work has quantified the unique phenotypic clinical presentations of FTD among post-9/11 era veterans. To identify phenotypes of FTD using natural language processing (NLP) aided medical chart reviews of post-9/11 era U.S. military Veterans diagnosed with FTD in Veterans Health Administration care. A medical record chart review of clinician/provider notes was conducted using a Natural Language Processing (NLP) tool, which extracted features related to cognitive dysfunction. NLP features were further organized into seven Research Domain Criteria Initiative (RDoC) domains, which were clustered to identify distinct phenotypes. Veterans with FTD were more likely to have notes that reflected the RDoC domains, with cognitive and positive valence domains showing the greatest difference across groups. Clustering of domains identified three symptom phenotypes agnostic to time of an individual having FTD, categorized as Low (16.4%), Moderate (69.2%), and High (14.5%) distress. Comparison across distress groups showed significant differences in physical and psychological characteristics, particularly prior history of head injury, insomnia, cardiac issues, anxiety, and alcohol misuse. The clustering result within the FTD group demonstrated a phenotype variant that exhibited a combination of language and behavioral symptoms. This phenotype presented with manifestations indicative of both language-related impairments and behavioral changes, showcasing the coexistence of features from both domains within the same individual. This study suggests FTD also presents across a continuum of severity and symptom distress, both within and across variants. The intensity of distress evident in clinical notes tends to cluster with more co-occurring conditions. This examination of phenotypic heterogeneity in clinical notes indicates that sensitivity to FTD diagnosis may be correlated to overall symptom distress, and future work incorporating NLP and phenotyping may help promote strategies for early detection of FTD.

Review of Leishmaniasis Treatment: Can We See the Forest through the Trees?

There are three known clinical syndromes of leishmaniasis: cutaneous (CL), mucocutaneous (MCL), and visceral disease (VL). In MCL and VL, treatment must be systemic (either oral or intravenous), while CL treatment options vary and include observation-only localized/topical treatment, oral medications, or parenteral drugs. Leishmaniasis treatment is difficult, with several factors to be considered. First, the efficacy of treatments varies among different species of parasites prevalent in different areas on the globe, with each species having a unique clinical presentation and resistance profile. Furthermore, leishmaniasis is a neglected tropical disease (NTD), resulting in a lack of evidence-based knowledge regarding treatment. Therefore, physicians often rely on case reports or case series studies, in the absence of randomized controlled trials (RCT), to assess treatment efficacy. Second, defining cure, especially in CL and MCL, may be difficult, as death of the parasite can be achieved in most cases, while the aesthetic result (e.g., scars) is hard to predict. This is a result of the biological nature of the disease, often diagnosed late in the course of disease (with possible keloid formation, etc.). Third, physicians must consider treatment ease of use and the safety profile of possible treatments. Thus, topical or oral treatments (for CL) are desirable and promote adherence. Fourth, the cost of the treatment is an important consideration. In this review, we aim to describe the diverse treatment options for different clinical manifestations of leishmaniasis. For each currently available treatment, we will discuss the various considerations mentioned above (efficacy, ease of use, safety, and cost).

Hemolytic Disease in Newborn Due to Jka Antibody: A Unique Clinical Presentation

Hemolytic disease in newborn results from alloimmune-mediated destruction of fetal or neonatal red blood cells caused by maternal alloantibodies. While ABO and Rh (D) incompatibilities are common causes, other minor antigenic mismatches such as Kidd are relatively infrequent. Here, we report a case of a female infant displaying conjugated hyperbilirubinemia and hepato-splenomegaly. Lab tests revealed both mother’s and baby’s blood groups as A positive, along with elevated reticulocyte count and a positive direct antiglobulin test. An abdominal ultrasound unveiled inspissated bile syndrome, likely due to calcium bilirubin sludge, leading to the conjugated hyperbilirubinemia. Further assessment revealed the infant and the father had a JKa-positive RBC phenotype, while the mother had a JKa-negative phenotype. This case highlights the significance of blood group antigen beyond the Rh system as a potential cause of hemolytic disease in newborn.