Rev Esp Patol. 2024 Jan-Mar;57(1):53-58. doi: 10.1016/j.patol.2023.04.003. Epub 2023 Jul 5.

ABSTRACT

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare disease with a poor prognosis. It frequently affects the skin; indeed, dermal lesions may be the first clinical manifestation. We report three cases of BPDCN where the patients presented with skin lesions and describe the clinical, histopathological and immunohistochemical findings, its molecular characteristics and metastatic work-up. One of the patients remains in a clinical trial with IMGN632, a molecule directed against CD123, while the other two patients died after different therapeutic regimens. BPDCN is a complex diagnostic challenge which, together with its poor prognosis, requires close clinical-pathological cooperation in order to accelerate its diagnosis and offer early therapeutic alternatives with drugs directed against specific molecular targets.

PMID:38246711 | DOI:10.1016/j.patol.2023.04.003

Medicine (Baltimore). 2024 Jan 19;103(3):e37005. doi: 10.1097/MD.0000000000037005.

ABSTRACT

RATIONALE: A huge hypertrophic scar formation secondary to chronic ingrown toe nail mimicking tumor is a rare disease. It is not only causing concerns cosmetically, but also hindering normal daily activities physically and socially. In this paper, we present an unusual case of bilateral ingrown nails with different phases. One resulted in a large hypertrophic scar caused by stimulation from secondary to chronic ingrown nail.

PATIENT CONCERNS AND DIAGNOSIS: A 44-year-old man with a huge mass (7 × 4 × 8.5 cm) in his right great toe and inflamed ingrown nail in his left great toe visited the clinic. The mass in the right toe showed an irregular and bizarre shape with a stellate ulcer (2 × 2 cm) at the distal end. After removing an ingrown nail 3 years ago with minor repetitive trauma, self-managed wound has grown into a tumor-like mass, resulting in intolerable discomfort. In gross appearance, a stalk appeared to originate from the lateral side of the nail bed with the ingrown nail in the great toe showing inflamed medial and lateral gutter and causing redness and tenderness. Huge hypertrophic scar formation secondary to chronic ingrown toe nail mimicking tumor is a rare disease that is not only causing a cosmetic concern, but also hindering normal daily activities physically and socially.

INTERVENTION AND OUTCOMES: Excisional biopsy was performed for both great toes. Biopsy confirmed chronic ulcerative inflammation with a hypertrophic scar. The resection site healed and persisted well at 12 months after surgery.

CONCLUSION: Our unusual case suggests that the natural course of an untreated ingrown toe nail may result in hypertrophic scar extending far to mimic tumorous conditions.

PMID:38241575 | PMC:PMC10798770 | DOI:10.1097/MD.0000000000037005

Medicine (Baltimore). 2024 Jan 19;103(3):e36920. doi: 10.1097/MD.0000000000036920.

ABSTRACT

RATIONALE: Pure white cell aplasia (PWCA) is a rare paraneoplastic syndrome that occurs in patients with thymomas. Currently, the pathogenesis and treatment of this disease remain in the exploratory stage.

PATIENT CONCERNS: We report a 68-year-old woman with thymoma experienced PWCA involvement as her first presentation. The patient had high fever and agranulocytosis at the onset of the disease. The white blood cell count in the complete blood count was 1.9 × 109/L with a neutrophil of 0.1 × 109/L. The bone marrow aspirates showed decreased granulocyte proliferation. Computed tomography showed a large mass in the anterior mediastinum.

DIAGNOSES: The final diagnosis of our patient was PWCA and thymoma.

INTERVENTIONS: She underwent a thymectomy and cyclosporine A administration during first remission.

OUTCOMES: Long-term remission was achieved following the readministration of cyclosporine A after the disease recurrence.

LESSONS: PWCA or agranulocytosis with thymoma has been confirmed to be an extremely rare disease. Thymomas with PWCA correlate with autoimmunity. From this case study and the literature review, we concluded that the pathogenesis of thymomas in PWCA is mainly related to the activation of autoreactive T cells. Thymectomy and the immunosuppressive drug, cyclosporine A, were chosen for treatment. The patient's granulocyte levels were unable to recover after surgery because of the inability to promptly clear activated T cells. After surgery, cyclosporine A continued to take for a long time. Thymectomy combined with prolonged cyclosporine A administration may be an effective method for treating this rare disease.

PMID:38241556 | PMC:PMC10798751 | DOI:10.1097/MD.0000000000036920

Orphanet J Rare Dis. 2024 Jan 18;19(1):18. doi: 10.1186/s13023-024-03018-y.

ABSTRACT

BACKGROUND: Vascular anomalies (VAs) are rare congenital disorders that can cause pain, disfigurement, coagulopathy, asymmetric growth, and disability. Patients with complex VAs experience multiple barriers to accessing expert care. It is imperative to understand which factors support these patients' ability to navigate the healthcare system.

RESULTS: We surveyed adult patients with VAs using previously validated measures, recruiting participants from five patient advocacy groups and multidisciplinary VA clinics. The primary outcome was self-reported ability to access needed medical care, using the "Navigating the Healthcare System" subscale of the Health Literacy Questionnaire. We evaluated factors associated with the ability to navigate the healthcare system using multivariate linear regression (n = 136). We also performed an exploratory model that included the primary care doctor's knowledge of VAs for the subset of participants with a primary care doctor (n = 114). Participants were predominantly women (n = 90, 66%), White and non-Hispanic (n = 109, 73%), and college-educated (n = 101, 73%). Most participants had PIK3CA-Related Overgrowth Spectrum (n = 107, 78%). Most participants reported that navigating the healthcare system was "sometimes" or "usually difficult" (mean score 16.4/30, standard deviation 5.6). In multivariate linear regression, ability to navigate the healthcare system was associated positively with quality of information exchange (β = 0.38, 95% Confidence Interval (CI) 0.22 to 0.55, p <.001) and whether patients had VA specialists (β = 2.31, 95% CI 0.35 to 4.28, p =.021), but not associated with patient self-advocacy, anxiety, education, age, race and ethnicity, gender, or having a primary care doctor. In exploratory analysis of participants with primary care doctors, ability to navigate the healthcare system was positively associated with quality of information exchange (β = 0.27, 95% CI 0.09 to 0.45, p =.004), having a VA specialist (β = 2.31, 95% CI 0.22 to 4.39, p =.031), and primary care doctors' VA knowledge (β = 0.27, 95% CI 0.04 to 0.50, p =.023).

CONCLUSION: Patients with VAs struggle to navigate the healthcare system. High-quality information from clinicians and more knowledgeable primary care doctors might help patients to access needed care. Relying on patient self-advocacy is insufficient. Future efforts should focus on patient-directed and clinician-directed educational interventions. Additionally, future work should assess the structural barriers that impede healthcare access for these patients.

PMID:38238812 | PMC:PMC10797881 | DOI:10.1186/s13023-024-03018-y

medRxiv. 2023 Dec 27:2023.12.22.23300468. doi: 10.1101/2023.12.22.23300468. Preprint.

ABSTRACT

Unsolved Mendelian cases often lack obvious pathogenic coding variants, suggesting potential non-coding etiologies. Here, we present a single cell multi-omic framework integrating embryonic mouse chromatin accessibility, histone modification, and gene expression assays to discover cranial motor neuron (cMN) cis-regulatory elements and subsequently nominate candidate non-coding variants in the congenital cranial dysinnervation disorders (CCDDs), a set of Mendelian disorders altering cMN development. We generated single cell epigenomic profiles for ~86,000 cMNs and related cell types, identifying ~250,000 accessible regulatory elements with cognate gene predictions for ~145,000 putative enhancers. Seventy-five percent of elements (44 of 59) validated in an in vivo transgenic reporter assay, demonstrating that single cell accessibility is a strong predictor of enhancer activity. Applying our cMN atlas to 899 whole genome sequences from 270 genetically unsolved CCDD pedigrees, we achieved significant reduction in our variant search space and nominated candidate variants predicted to regulate known CCDD disease genes MAFB, PHOX2A, CHN1, and EBF3 - as well as new candidates in recurrently mutated enhancers through peak- and gene-centric allelic aggregation. This work provides novel non-coding variant discoveries of relevance to CCDDs and a generalizable framework for nominating non-coding variants of potentially high functional impact in other Mendelian disorders.

PMID:38234731 | PMC:PMC10793524 | DOI:10.1101/2023.12.22.23300468

J Med Chem. 2024 Feb 8;67(3):1690-1700. doi: 10.1021/acs.jmedchem.3c02165. Epub 2024 Jan 17.

ABSTRACT

Expedited development and approval pathways at the Food and Drug Administration (FDA) such as Priority review, Fast Track Designation, Breakthrough Designation, and Accelerated Approval are programs available to drug sponsors that aim to incentivize and expedite the delivery of drugs to patients in need. In addition, other incentive programs such as Orphan Drug Designation (ODD), Qualified Infectious Disease Product Designation (QIDP), and Rare Pediatric Disease Designation (RPDD) are available to drug sponsors to help motivate development of drugs that may have lower economic incentive for commercialization. These programs have been largely effective, and many new innovative drugs since 2010 have accessed these programs. This Perspective highlights how these programs have been used in recent FDA drug approvals and discusses future ways sponsors and regulatory agencies may further enable development of these innovative drugs in the most expeditious fashion.

PMID:38233132 | DOI:10.1021/acs.jmedchem.3c02165

Pediatr Neurol. 2023 Nov 23;152:63-72. doi: 10.1016/j.pediatrneurol.2023.11.005. Online ahead of print.

ABSTRACT

BACKGROUND: Trofinetide was approved by the US Food and Drug Administration for the treatment of Rett syndrome (RTT) in March 2023. Benefiting the ability to communicate in RTT is often identified as the most important caregiver goal for new therapies. This analysis reports the communication-related end points from the phase 3 LAVENDER study of trofinetide in RTT.

METHODS: Females with RTT, aged five to 20 years, were randomized 1:1 to trofinetide or placebo for 12 weeks. Secondary efficacy end points related to communication were based on change from baseline to week 12 and included the caregiver-rated Communication and Symbolic Behavior Scales Developmental Profile™ Infant-Toddler Checklist (CSBS-DP-IT) Social Composite score (key secondary end point; scores ranged from 0 to 26 [higher scores indicated better communication]) and novel clinician rating scales (0 [normal] to 7 [severe impairment]) measuring the ability to communicate choices nonverbally (RTT-COMC) and verbally (RTT-VCOM).

RESULTS: Trofinetide demonstrated a statistically significant difference versus placebo for the CSBS-DP-IT Social Composite score (least squares mean [LSM] difference = 1.0; 95% confidence interval [CI], 0.3 to 1.7; P = 0.0064; Cohen's d effect size = 0.43) and a nominally significant difference for the RTT-COMC (LSM difference: -0.3; 95% CI, -0.6 to -0.0; P = 0.0257; Cohen's d effect size = 0.36). As expected, there was no difference for the RTT-VCOM.

CONCLUSIONS: Significant treatment benefit for trofinetide versus placebo was observed in scales measuring the ability to communicate. These scales may be appropriate for future clinical studies in RTT and other neurodevelopmental disorders.

PMID:38232652 | DOI:10.1016/j.pediatrneurol.2023.11.005

J Clin Immunol. 2024 Jan 17;44(2):47. doi: 10.1007/s10875-023-01644-y.

ABSTRACT

PURPOSE: Inborn errors of immunity (IEI) represent a heterogeneous group of rare genetically determined diseases. In some cases, patients present with complex or atypical phenotypes, not fulfilling the accepted diagnostic criteria for IEI and, thus, at high risk of misdiagnosis or diagnostic delay. This study aimed to validate a platform that, through the opinion of immunologist experts, improves the diagnostic process and the level of care of patients with atypical/complex IEI.

METHODS: Here, we describe the functioning of the IEI-Virtual Consultation System (VCS), an innovative platform created by the Italian Immunodeficiency Network (IPINet).

RESULTS: In the validation phase, from January 2020 to June 2021, 68 cases were entered on the IEI-VCS platform. A final diagnosis was achieved in 35/68 cases (51%, 95% CI 38.7 to 64.2). In 22 out of 35 solved cases, the diagnosis was confirmed by genetic analysis. In 3/35 cases, a diagnosis of secondary immunodeficiency was made. In the remaining 10 cases, an unequivocal clinical and immunological diagnosis was obtained, even though not substantiated by genetic analysis.

CONCLUSION: From our preliminary study, the VCS represents an innovative and useful system to improve the diagnostic process of patients with complex unsolved IEI disorders, with benefits both in terms of reduction of time of diagnosis and access to the required therapies. These results may help the functioning of other international platforms for the management of complex cases.

PMID:38231401 | PMC:PMC10794402 | DOI:10.1007/s10875-023-01644-y

BMC Pediatr. 2024 Jan 8;24(1):28. doi: 10.1186/s12887-023-04492-2.

ABSTRACT

BACKGROUND: Pediatric myelodysplastic syndromes (MDS) are rare disorders with an unrevealed pathogenesis. Our aim is to explore the role of genetic factors in the pathogenesis of MDS in children with different outcomes and to discover the correlation between genetic features and clinical outcomes as well as disease characteristics.

METHODS: We conducted an analysis of archived genetic data from 26 patients diagnosed with pediatric MDS at our institution between 2015 and 2021, examining the association between different genetic characteristics and clinical manifestations as well as prognosis. Additionally, We presented three cases with distinct genetic background and outcomes as examples to elaborate the role of genetic factors in pediatric MDS with different prognoses.

RESULTS: Genetic variations were detected in 13 out of the 26 patients, including 8 patients with co-occurrence of somatic and germline mutations (CSGMs) and 5 patients with somatic mutations alone. Our analysis revealed that advanced MDS (4/8, 50% vs. 1/5, 20% and 4/11, 36.4%), PD (3/8, 37.5% vs. 1/5, 20% and 1/11 9.1%), and TD (6/8, 75% vs. 2/5, 40% and 2/11, 18.2%) were more common in patients with CSGMs than those with somatic mutations alone or without any mutations. We also found out in our study that 8 patients with CSGMs had evidently different clinical outcomes, and we presented 3 of them as examples for elaboration. Case 1 with germline and somatic mutations of unknown significance had a relatively slow disease course and a good prognosis. Case 2 with compound heterozygous germline SBDS variants and somatic mutations like del20q had a stable disease course and a reversed outcome. Case 3 with a germline GATA2 variant and somatic mutations including - 7 had a rapidly progressive disease course and a worst prognosis.

CONCLUSION: Our findings indicate that genetic background of pediatric MDS is closely linked with disease characteristics as well as outcomes and that CSGMs may lead to disease progression. It should be emphasized that the interaction between certain germline variants and somatic mutations, such as SBDS and del20q, may result in hematopoietic stem cell adaptation (improved hematopoiesis) and reversed clinical outcomes, which can facilitate the development of targeted therapy.

PMID:38191334 | DOI:10.1186/s12887-023-04492-2

BMJ Case Rep. 2024 Jan 8;17(1):e258045. doi: 10.1136/bcr-2023-258045.

ABSTRACT

Extramammary Paget disease is a rare dermatological condition resembling Paget disease that occurs most commonly in the anogenital area and axilla. We present the case of an elderly male who had come with complaints of an itchy, erythematous and raised lesion in the perianal region for 3 months that did not respond to antifungals. A biopsy was taken from the lesion site and the diagnosis was confirmed by histopathological examination. It is important to be aware of conditions like extramammary Paget disease when an elderly individual presents with a non-specific pruritic lesion in the perianal area that is non-responsive to treatment; the diagnosis of which can be made only by doing a biopsy from the concerned site. This highlights the importance of histopathological examination in such ambiguous cases.

PMID:38191219 | DOI:10.1136/bcr-2023-258045

Health Aff (Millwood). 2024 Jan;43(1):18-26. doi: 10.1377/hlthaff.2023.00219.

ABSTRACT

The Orphan Drug Act of 1983 was enacted to provide financial incentives to stimulate drug development for rare diseases. In recent years, concerns have been raised regarding these orphan drugs, including how many are being approved for both rare and common diseases and the number of subsequent indication approvals. Policy makers have suggested modifications to the Orphan Drug Act's incentives to address these concerns. In this study we investigated the approval "family trees" of orphan drugs. We found that 491 novel orphan drugs were approved between 1990 and 2022. To date, 65 percent have been approved for a single rare disease, 15 percent have been approved for multiple rare diseases, and 20 percent have been approved for both rare and common diseases. Ten percent of orphan drugs received a subsequent indication approval for a pediatric population of an orphan disease. Revenue estimates from 2021 show that one-third of the drugs approved for both rare and common indications and 6 percent of rare-only drugs were among the 200 top-selling drugs worldwide. The results have implications for the possible externalities of modifying the incentives of the Orphan Drug Act, such as a potential decrease in the initiation of programs to develop pediatric rare disease drugs.

PMID:38190603 | DOI:10.1377/hlthaff.2023.00219

Indian J Anaesth. 2023 Nov;67(Suppl 4):S300-S301. doi: 10.4103/ija.ija_406_23. Epub 2023 Nov 21.

NO ABSTRACT

PMID:38187970 | PMC:PMC10768896 | DOI:10.4103/ija.ija_406_23

JIMD Rep. 2023 Nov 27;65(1):17-24. doi: 10.1002/jmd2.12401. eCollection 2024 Jan.

ABSTRACT

Mucopolysaccharidosis II (MPS II) is a rare, life-limiting lysosomal storage disease caused by reduced iduronate-2-sulfatase activity. Patients experience broad ranging signs and symptoms, including bone and joint manifestations. This study reported on orthopedic involvement and management in patients with MPS II using 15 years of data from the Hunter Outcome Survey (HOS). Of the 245 patients in the study population, 90.2% had skeletal deformity (median onset, 2.8 years), 76.7% had upper body stiffness (onset, 4.2 years), and 61.2% had lower body stiffness (onset, 5.3 years); 63.7% of patients had at least three joint manifestations. Orthopedic manifestations were common in adults and children with MPS II, and in patients with and without cognitive impairment. Joint range of motion (JROM) was restricted in all joints assessed (shoulder, elbow, hip, wrist, knee, and ankle). Little correlation was observed between JROM measurements, subjective reports of joint stiffness and limited function, and 6-minute walk test results. Patients with joint stiffness and limited function were generally more likely to have central and peripheral nervous system, pulmonary, and cardiovascular manifestations than those without these symptoms. Carpal tunnel decompression was the most common orthopedic surgery (recorded in 49/245 patients [20.0%]), but orthopedic surgeries were uncommon overall. Our findings highlight the need for routine monitoring of orthopedic manifestations using multiple assessment types in patients with MPS II to help inform clinical decision-making and improve patient quality of life. They also underline the contribution of factors other than orthopedic manifestations to the walking ability of patients with MPS II.

PMID:38186847 | PMC:PMC10764199 | DOI:10.1002/jmd2.12401

BMC Med Res Methodol. 2024 Jan 6;24(1):5. doi: 10.1186/s12874-023-02125-x.

ABSTRACT

BACKGROUND: In the last decades, medical research fields studying rare conditions such as spinal cord injury (SCI) have made extensive efforts to collect large-scale data. However, most analysis methods rely on complete data. This is particularly troublesome when studying clinical data as they are prone to missingness. Often, researchers mitigate this problem by removing patients with missing data from the analyses. Less commonly, imputation methods to infer likely values are applied.

OBJECTIVE: Our objective was to study how handling missing data influences the results reported, taking the example of SCI registries. We aimed to raise awareness on the effects of missing data and provide guidelines to be applied for future research projects, in SCI research and beyond.

METHODS: Using the Sygen clinical trial data (n = 797), we analyzed the impact of the type of variable in which data is missing, the pattern according to which data is missing, and the imputation strategy (e.g. mean imputation, last observation carried forward, multiple imputation).

RESULTS: Our simulations show that mean imputation may lead to results strongly deviating from the underlying expected results. For repeated measures missing at late stages (> = 6 months after injury in this simulation study), carrying the last observation forward seems the preferable option for the imputation. This simulation study could show that a one-size-fit-all imputation strategy falls short in SCI data sets.

CONCLUSIONS: Data-tailored imputation strategies are required (e.g., characterisation of the missingness pattern, last observation carried forward for repeated measures evolving to a plateau over time). Therefore, systematically reporting the extent, kind and decisions made regarding missing data will be essential to improve the interpretation, transparency, and reproducibility of the research presented.

PMID:38184529 | DOI:10.1186/s12874-023-02125-x

Pediatr Rheumatol Online J. 2024 Jan 5;22(1):12. doi: 10.1186/s12969-023-00947-z.

ABSTRACT

Haploinsufficiency of A20 (HA20) is a rare monogenic disease caused by heterozygous loss-of-function mutations in the tumor necrosis factor alpha-induced protein 3 (TNFAIP3) gene located on chromosome 6q23.3. The majority of disease-causing mutations in most cases of HA20 comprise single nucleotide variations, small insertions, or deletions in TNFAIP3, which result in a premature termination codon and subsequent disruption of its anti-inflammatory role. Large deletions have been reported sporadically. HA20 patients may present with a variety of autoinflammatory and autoimmune features during early childhood; however, cases with neonatal onset are rare. Here, we describe a Chinese neonate presenting with concomitant inflammatory and other syndromic manifestations caused by a 5.15 Mb interstitial deletion in chromosome 6; these deletions affect TNFAIP3. Taken together, the data extend the clinical and genetic spectra of HA20.

PMID:38183052 | PMC:PMC10770963 | DOI:10.1186/s12969-023-00947-z

J Mol Neurosci. 2024 Jan 5;74(1):2. doi: 10.1007/s12031-023-02184-1.

ABSTRACT

Primary familial brain calcification (PFBC) is a rare disorder that can manifest with a wide spectrum of motor, cognitive, and psychiatric symptoms or even remain asymptomatic. Alzheimer disease (AD) is a common condition that typically starts as a progressive amnestic disorder and progresses to major cognitive impairment. Accurately attributing an etiology to cognitive impairment can sometimes be challenging, especially when multiple pathologies with potentially overlapping symptomatology contribute to the clinical phenotype. Here, we present the case of two patients with autosomal dominant PFBC and non-monogenic AD. Cerebrospinal fluid (CSF) biomarker analysis combined with genetic testing permitted the dual diagnosis. We emphasize the importance of thoroughly characterizing the patient's phenotype at onset and during the follow-up. Particular attention is placed on psychiatric symptoms given that both patients had a history of mood disorder, a frequent condition in the general population and in neurological diseases. We also discuss and challenge the paradigm of seeking a single diagnosis explaining all symptoms, remembering the possibility of a rare disease co-occurring with a common one.

PMID:38180527 | DOI:10.1007/s12031-023-02184-1

Genome Med. 2024 Jan 4;16(1):4. doi: 10.1186/s13073-023-01276-2.

ABSTRACT

BACKGROUND: Next-generation sequencing (NGS) has significantly transformed the landscape of identifying disease-causing genes associated with genetic disorders. However, a substantial portion of sequenced patients remains undiagnosed. This may be attributed not only to the challenges posed by harder-to-detect variants, such as non-coding and structural variations but also to the existence of variants in genes not previously associated with the patient's clinical phenotype. This study introduces EvORanker, an algorithm that integrates unbiased data from 1,028 eukaryotic genomes to link mutated genes to clinical phenotypes.

METHODS: EvORanker utilizes clinical data, multi-scale phylogenetic profiling, and other omics data to prioritize disease-associated genes. It was evaluated on solved exomes and simulated genomes, compared with existing methods, and applied to 6260 knockout genes with mouse phenotypes lacking human associations. Additionally, EvORanker was made accessible as a user-friendly web tool.

RESULTS: In the analyzed exomic cohort, EvORanker accurately identified the "true" disease gene as the top candidate in 69% of cases and within the top 5 candidates in 95% of cases, consistent with results from the simulated dataset. Notably, EvORanker outperformed existing methods, particularly for poorly annotated genes. In the case of the 6260 knockout genes with mouse phenotypes, EvORanker linked 41% of these genes to observed human disease phenotypes. Furthermore, in two unsolved cases, EvORanker successfully identified DLGAP2 and LPCAT3 as disease candidates for previously uncharacterized genetic syndromes.

CONCLUSIONS: We highlight clade-based phylogenetic profiling as a powerful systematic approach for prioritizing potential disease genes. Our study showcases the efficacy of EvORanker in associating poorly annotated genes to disease phenotypes observed in patients. The EvORanker server is freely available at https://ccanavati.shinyapps.io/EvORanker/ .

PMID:38178268 | PMC:PMC10765705 | DOI:10.1186/s13073-023-01276-2

Ned Tijdschr Geneeskd. 2023 Nov 23;167:D7753.

ABSTRACT

When confronted with an unexpected clinical observation, such as a remarkable symptom in a patient with an unrelated rare disease, clinicians increasingly apply online literature search to support the observed correlation. Against a background of an exponential rise in medical publications and the well-documented problem of publication bias, the easy access to literature carries the risk of suggesting spurious correlations. The current paper expounds on this phenomenon. Queries in medical search engines often provide a number of hits, regardless of the plausibility of the correlation searched for. To quantify this, we recently performed a study involving 30.000 automated queries in PubMed using completely random search terms drawn from lists of diseases, symptoms and medications. This provided a background rate of PubMed hits. The data support that several hits by no means automatically indicate a relevant correlation, and underline need for judicious critical appraisal when searching for a correlation observed in daily practice.

PMID:38175564

Diagn Pathol. 2024 Jan 3;19(1):2. doi: 10.1186/s13000-023-01427-4.

ABSTRACT

BACKGROUND: Benign metastasizing leiomyoma (BML) is a rare disease with an unknown etiopathogenesis that mostly affects middle-aged women with uterine leiomyoma. Many metastatic nodules outside the uterus characterize the condition. The metastases are smooth muscle lesions without malignancy. Morphologically and immunohistochemically, they resemble uterine leiomyomas, indicating a shared clonal origin. The lungs are the most prevalent site for incidental metastasis detection. BML has a relatively slow progression and good prognosis, and historically, there has been a lack of established guidelines for its treatment.

CASE PRESENTATION: Herein, we report a case of BML in a patient with multiple metastases. Through extensive histological and immunohistochemical analyses, this complex case enabled not only the definitive diagnosis of BML, but also shed light on its complex etiopathogenesis.

CONCLUSION: This study presents novel histology evidence suggesting a potential causal relationship between metaplasia and the development of BML.

PMID:38172926 | PMC:PMC10765933 | DOI:10.1186/s13000-023-01427-4

BMC Ophthalmol. 2024 Jan 3;24(1):5. doi: 10.1186/s12886-023-03254-z.

ABSTRACT

BACKGROUND: Torpedo maculopathy (TM) is a rare, congenital condition characterized by an oval-shaped, chorioretinal lesion in the temporal macula of unknown etiology. To our knowledge, the longest reported follow-up of TM is 5 years. Herein we report 10 years of follow-up on two patients with TM to further characterize the long-term natural history of the condition.

CASE REPORTS: Two patients with torpedo maculopathy were examined at baseline and then again at 5 years and 10 years from baseline. Eyes were evaluated using color fundus photography, automated perimetry, fundus autofluorescence and spectral domain optical coherence tomography. Visual function of both patients remained stable throughout the observation period. In case 1, there was no evidence of change in lesion morphology over the 10 year observation period. Case 2 showed progression of cystic degeneration of the neurosensory retina within the torpedo lesion. Case 1 reported a history of supernumerary teeth and underwent gene sequence with deletion/duplication analyses of the APC gene but no clinically significant variants were detected.

CONCLUSIONS: Our findings support the position that TM is a nonprogressive condition with long-term stability of visual function. Genetic analysis of case 1 failed to detect any association with Gardner syndrome.

PMID:38172762 | DOI:10.1186/s12886-023-03254-z