Pathological Evidence Research Articles

A Case of Post Viral Acute Longitudinal Extensive Transverse Myelitis (LETM): MOGAD- A New Horizon

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently identified autoimmune disorder that presents in both adults and children. It is a group of central nervous system demyelinating diseases caused by auto antibodies against myelin oligosaccharide protein, a myelin sheath component protein, and present with a variety of symptoms, including optic neuritis, longitudinal extensive transverse myelitis (LETM), acute disseminated encephalomyelitis (ADEM), brainstem encephalitis, and corticobasal encephalitis. Although there are clinical phenotypic overlaps between MOGAD, multiple sclerosis, and aquaporin-4 antibody-associated neuromyelitis optica spectrum disorder (NMOSD) cumulative biological, clinical, and pathological evidence discriminates between these conditions. Here, we present a case of a young male with acute onset of spastic paraplegia with sphincters involvement and patchy loss of pinprick sensation with positive Anti-MOG Antibody shortly after viral febrile illness. Bangladesh Crit Care J March 2024; 12 (1): 62-67

Determinants and Biomarkers of Progression Independent of Relapses in Multiple Sclerosis.

Clinical, pathological, and imaging evidence in multiple sclerosis (MS) suggests that a smoldering inflammatory activity is present from the earliest stages of the disease and underlies the progression of disability, which proceeds relentlessly and independently of clinical and radiological relapses (PIRA). The complex system of pathological events driving "chronic" worsening is likely linked with the early accumulation of compartmentalized inflammation within the central nervous system as well as insufficient repair phenomena and mitochondrial failure. These mechanisms are partially lesion-independent and differ from those causing clinical relapses and the formation of new focal demyelinating lesions; they lead to neuroaxonal dysfunction and death, myelin loss, glia alterations, and finally, a neuronal network dysfunction outweighing central nervous system (CNS) compensatory mechanisms. This review aims to provide an overview of the state of the art of neuropathological, immunological, and imaging knowledge about the mechanisms underlying the smoldering disease activity, focusing on possible early biomarkers and their translation into clinical practice. ANN NEUROL 2024;96:1-20.

Anatomical Structures at Risk in Percutaneous Distal Bunionette Correction

Introduction/Purpose: Bunionette deformity affects 23% of the population and has numerous surgical options, including a minimally invasive approach (MIA) to decrease complications. Percutaneous surgery is favored by patients as it decreases pain, inflammation, and noticeable incision sites. Three possible osteotomy sites have been identified: proximal, diaphyseal, and distal. The study investigates the anatomic structures at risk during distal osteotomy of bunionette deformity using a Shannon burr. The distal osteotomy site was on average greater than 8mm from the extensor digitorum longus and adductor digiti minimi while it was 1.64mm from the lateral dorsal cutaneous nerve. The study highlighted the challenges posed by minimally invasive approaches to treating bunionette deformity and the need for cautious consideration when utilizing percutaneous methods. Methods: Eleven fresh frozen below-knee amputated foot and ankle cadavers were used for this study. Cadavers were allowed to thaw for 12 hours at room temperature before performing any tissue handling. All cadavers were visually inspected for evidence of gross pathology. Fluoroscopic radiographs were used to inspect for evidence of preexisting pathology of the fifth metatarsal. All cadavers with gross pathology or radiographic fifth metatarsal pathology were excluded from the study. All procedures were performed by a fellowship trained orthopaedic foot and ankle surgeon. Results: All eleven cadavers met the inclusion criteria for this study. The average age of the patients was 66.6 +/- 20.1 years. There were five female feet and six male feet. There were seven right feet and four left feet. Distance from the percutaneous access site was measured to structures at potential risk. The closest structure at risk was the lateral dorsal cutaneous nerve (LDCN) (1.64 mm), which was contacted 2/11 times and transected both times. The extensor digitorum longus (EDL) and abductor digiti minimi (ADM) had no instances of contact during the procedure. Dissection allowed for the identification of structures at risk and the assessment of osteotomy. All procedures resulted in a complete osteotomy. Conclusion: Overall, distal percutaneous bunionette osteotomy is largely safe. Structures pertinent to the surgery were identified with ease and were intact after osteotomy with a Shannon burr. Anatomic variations of LDCN can present challenges to the procedure. Meticulous dissection and judicious use of fluoroscopy can help prevent further damage. Surgeons should be aware of anatomic variations in order to proceed safely.

Prevalence of Aortic Root Pathologies in Platypnea-Orthodeoxia Syndrome Secondary to Intra-Cardiac Shunts.

Atrial septal defects can allow right to left shunting of venous blood which presents clinically as platypnea-orthodeoxia syndrome. It is believed that concomitant presence of aortic root pathologies increases the likelihood of shunting. The study included a review of 510 articles listed in PubMed of patients with platypnea-orthodeoxia syndrome. Case reports of patients with extra-cardiac etiologies of platypnea-orthodeoxia were excluded. We reviewed 191 case reports, and 98 cases (51.3%) had evidence of concomitant aortic root pathology. Furthermore, of the remaining 93 case reports, 69 ones excluded any mention of the nature of the aortic root altogether, further suggesting that this is an underreported number. There is a high prevalence of aortic root pathologies in patients with platypnea-orthodeoxia syndrome secondary to intra-cardiac shunts. In patients with unexplained hypoxemia and incidental finding of aortic root pathology, it may be worthwhile to obtain postural oxygen saturation measurements to exclude intra-cardiac shunts as the potential cause.

Review of Phenotypic Heterogeneity of Neuronal Intranuclear Inclusion Disease and NOTCH2NLC-Related GGC Repeat Expansion Disorders.

Neuronal intranuclear inclusion disease (NIID) is an underdiagnosed neurodegenerative disorder caused by pathogenic GGC expansions in NOTCH2NLC. However, an increasing number of reports of NOTCH2NLC GGC expansions in patients with Alzheimer disease, essential tremor, Parkinson disease, amyotrophic lateral sclerosis, and oculopharyngodistal myopathy have led to the proposal of a new concept known as NOTCH2NLC-related GGC repeat expansion disorders (NREDs). The majority of studies have mainly focused on screening for NOTCH2NLC GGC repeat variation in populations previously diagnosed with the associated disease, subsequently presenting it as a novel causative gene for the condition. These studies appear to be clinically relevant but do have their limitations because they may incorrectly regard the lack of MRI abnormalities as an exclusion criterion for NIID or overlook concomitant clinical presentations not typically observed in the associated diseases. Besides, in many instances within these reports, patients lack pathologic evidence or undergo long-term follow-up to conclusively rule out NIID. In this review, we will systematically review the research on NOTCH2NLC 5' untranslated region GGC repeat expansions and their association with related neurologic disorders, explaining the limitations of the relevant reports. Furthermore, we will integrate subsequent studies to further demonstrate that these patients actually experienced distinct clinical phenotypes of NIID.

Zoonotic potential of brucellosis in marine mammals

Brucellosis in marine mammals (cetacean and pinnipeds) has emerged in a very significant way during the last two decades. Currently Brucella ceti and Brucella pinnipedialis are the two recognized species in marine mammals, but available information is still limited. Several genotypes have been identified, and studies on the relationship between sequence type (ST) and organ pathogenicity or tropism have indicated differences in pathogenesis between B. ceti sequences in cetaceans. The zoonotic potential of this disease is based on the identification of the main sources of introduction and spread of Brucella spp. in the marine environment as well as on the factors of exposure of marine mammals and humans to the bacteria. This article is a bibliographical review on marine mammal brucellosis, including the features, sources and transmission modes of each Brucella species, as well as their potential pathogenicity in animals and humans. Different genotypes of marine Brucella spp have been isolated from marine mammal species but without any evidence of pathology induced by these bacteria. Associated lesions are variable and include subcutaneous abscesses, meningo-encephalomyelitis, pneumonia, myocarditis, osteoarthritis, orchitis, endometritis, placentitis and abortion. The isolation of marine B. spp from marine mammal respiratory parasites associated to lung injury has raised the intriguing possibility that they may serve as a vector for the transmission of this bacterium.The severity of marine B. spp remains unknown due to the lack of an estimate of the prevalence of this disease in marine mammals. The number of suspected human cases is still very limited. However, by analogy with other germs of the genus Brucella responsible for abortion in ruminants and for a febrile and painful state in human beings, prevention measures are essential. The significant increase in the number of strandings coupled with a high seroprevalence in certain species of marine mammals must be considered for people in direct or indirect contact with these animals. Ongoing epidemiological monitoring combined with extensive post-mortem examinations (necropsy, bacteriology and sequencing) of all species of stranded marine mammals would deepen knowledge on the zoonotic potential of marine Brucella species.

Abstract 7564: DNA methylation profiling identifies two distinct groups of oligosarcoma, IDH-mutant with distinct genetic alterations and clinical outcomes

Abstract DNA methylation has been extensively adopted for the classification of brain tumors and is endorsed by current neuropathology guidelines. Recently, oligosarcoma, IDH-mutant has been characterized as a distinct group of IDH mutant gliomas by DNA methylation classification. However, emerging studies revealed the variety in this group. Here, we employed DNA methylation-based t-SNE analysis to characterize oligosarcomas identified by the dkfz brain tumor classifier (v12.5). Thereby, we uncovered that oligosarcomas were segregated into two distinct groups, namely, subgroup A and subgroup B, which were further validated by genetic alterations and clinical outcomes. Next-generation Sequencing revealed subtype A tumors enriched with chr 1p/19q co-deletion, chr 6q loss, CDKN2A/B homogeneous deletion, TERT promoter mutation, and NF1 mutation, while subtype B tumors showed chr7 gaining and TP53 mutation. RNA sequencing and gene set enrichment analysis (GSEA) revealed that neuronal-tumor interaction and muscular progression pathways were more enriched in subtype A tumors. In contrast, subtype B tumors showed enrichment for angiogenesis and mTOR pathways. Additionally, inter-chromosomal fusion genes were more frequently found in subtype A tumors. Clinically, patients with subgroup A oligosarcomas manifested poorer survival and distinct imaging features in magnetic resonance imaging (MRI) compared to those with subgroup B. Collectively, we provided more cases of oligosarcoma, IDH-mutant, confirming the existence of this newly identified group, and revealed the subgroups harboring different genetic alterations and suffering different prognoses, providing new evidence for the molecular pathology in diffuse glioma. Citation Format: Kenan Zhang, Lingyu Liu, Xing Liu, Tao Jiang. DNA methylation profiling identifies two distinct groups of oligosarcoma, IDH-mutant with distinct genetic alterations and clinical outcomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7564.

Abstract 2586: Heterogeneous enhancement pattern of Gd-EOB-DTPA-enhanced MRI predicts vessels encapsulating tumor clusters (VETC)-positive hepatocellular carcinoma

Abstract Background: Vessels encapsulating tumor clusters (VETC) pattern is known as a distinct hepatocellular carcinoma (HCC) vascularization that correlates with angiogenic status, lower lymphocytic infiltration, and higher recurrence rates. Despite the molecular and clinical significance of VETC+ HCC, its characteristics on radiological imaging have not been clearly elucidated. We aimed to characterize VETC+ HCC on gadolinium-ethoxybenzyl-diethylene-triamine-pentaacetic acid-enhanced MR imaging (EOB-MRI) and provide pathological evidence. Method: We studied 204 surgically resected HCCs with preoperative EOB-MRI. VETC+ HCC was defined as ≥1% VETC occupied area evaluated by CD34 immunostaining. The visual pattern classification of the arterial and hepatobiliary phase images is shown in Table 1. To investigate the relationships between imaging patterns and VETC+ HCC, we evaluated immunohistochemical expression of h-caldesmon+ arterial vessel density (AVD) and OATP1B3. Result: In the arterial phase, VETC+ HCCs showed heterogeneous hypervascular pattern and homogeneous hypovascular pattern. Accordingly, VETC+ HCCs had lower AVD than VETC− HCCs, as well, VETC regions had lower AVD than other regions within the same tumor. In the hepatobiliary phase, VETC+ HCCs were observed more frequently in heterogeneous hyperintense pattern (36%) compared to homogeneous hyperintense pattern (5%). Hyperintensity in the hepatobiliary phase was correlated with high expression of OATP1B3. Among tumors with high OATP1B3 expression, VETC regions showed decreased expression of OATP1B3. Conclusion: VETC+ HCC showed reduced vascularity and heterogeneous hyperintensity in the hepatobiliary phase of EOB-MRI. These findings were explained by locally reduced AVD and downregulated OATP1B3 expression in the VETC regions. The potency to predict VETC+ HCCs by radiological findings could improve HCC treatment strategy. Relationship between enhancement patterns and VETC+ HCC in arterial and hepatobiliary phase Arterial phase Hypervascular/Homogeneous Hypervascular/Heterogeneous Hypovascular/Homogeneous Hypovascular/Heterogeneous Rim-like Number of tumors 68 103 8 15 11 VETC+ HCC (%) 6 (9%) 32 (31%) 3 (37%) 3 (20%) 1 (9%) Hepatobiliary phase Hyperintense/Homogeneous Hyperintense/Heterogeneous Hypointense/Homogeneous Hypointense/Heterogeneous Number of tumors 21 39 115 31 VETC+ HCC (%) 1 (5%) 14 (36%) 23 (20%) 8 (26%) Citation Format: Kosuke Matsuda, Akihisa Ueno, Junya Tsuzaki, Yutaka Kurebayashi, Ken Yamazaki, Masashi Tamura, Masahiro Jinzaki, Yuta Abe, Yasushi Hasegawa, Minoru Kitago, Michiie Sakamoto. Heterogeneous enhancement pattern of Gd-EOB-DTPA-enhanced MRI predicts vessels encapsulating tumor clusters (VETC)-positive hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2586.

Significance of Spread Through Air Spaces and Vascular Invasion in Early-stage Adenocarcinoma Survival: A Comprehensive Clinicopathologic Study of 427 Patients for Precision Management.

Spread through air spaces (STAS) is a novel invasive pattern of lung cancer associated with poor prognosis in non-small cell cancer (NSCLC). We aimed to investigate the incidence of STAS in a surgical series of adenocarcinomas (ADCs) resected in our thoracic surgery unit and to identify the association of STAS with other clinicopathological characteristics. We retrospectively enrolled patients with stage cT1a-cT2b who underwent resection between 2016 and 2022. For each case, a comprehensive pathologic report was accessible which included histotype, mitoses, pleural invasion, fibrosis, tumor infiltrating lymphocytes, necrosis, inflammation, vascular and perineural invasion, as well as STAS. PD-L1 expression was also investigated. A total of 427 patients with ADCs underwent surgery. Regarding overall survival (OS), no significant difference was observed between the STAS positive (STAS+) and STAS negative (STAS-) groups ( P =0.44). However, vascular invasion (VI) was associated with a poorer survival probability ( P =0.018). STAS+/VI+ patients had tendentially worse survival compared with STAS+/VI- ( P =0.089). ADCs with pathologic evidence of immune system (IS) activation (TILs>10% and PD-L1≥1) demonstrated significantly increased OS compared with ADCs with no IS and VI. In terms of recurrence rate, no statistical differences were found between the STAS+ and STAS- samples ( P =0.2). VI was also linked to a significantly elevated risk of recurrence ( P =0.0048). Our study suggests that in resected early-stage ADCs, STAS+ does not seem to influence recurrence or mortality. VI was instead an adverse pathologic prognostic factor for both survival and recurrence, whereas IS seemed to be protective.

Utility of MR Neurography for the Evaluation of Peripheral Trigeminal Neuropathies in the Postoperative Period.

Peripheral trigeminal neuropathies are assessed by MR neurography for presurgical mapping. In this clinical report, we aimed to understand the utility of MR neurography following nerve-repair procedures. We hypothesized that postoperative MR neurography assists in determining nerve integrity, and worsening MR neurography findings will corroborate poor patient outcomes. Ten patients with peripheral trigeminal neuropathy were retrospectively identified after nerve-repair procedures, with postsurgical MR neurography performed from July 2015 to September 2023. Postsurgical MR neurography findings were graded as per postintervention category and subcategories of the Neuropathy Score Reporting and Data System (NS-RADS). Descriptive statistics of demographics, inciting injury, injury severity, NS-RADS scoring, and clinical outcomes were obtained. There were 6 women and 4 men (age range, 25-73 years). Most injuries resulted from third molar removals (8/10), with an average time from the inciting event to nerve-repair surgery of 6.1 (SD, 4.6) months. In Neuropathy Score Reporting and Data System-Injury (NS-RADS I), NS-RADS I-4 injuries (neuroma in continuity) were found in 8/10 patients, and NS-RADS I-5 injuries were found in the remaining patients, all confirmed at surgery. Surgeries performed included microdissection with neurolysis, neuroma excision, and nerve allograft with Axoguard protection. Three patients with expected postsurgical MR neurography findings experienced either partial improvement or complete symptom resolution, while among 7 patient with persistent or recurrent neuropathy on postsurgical MR neurography, one demonstrated partial improvement of sensation, pain, and taste and one experienced only pain improvement; the remaining 5 patients demonstrated no improvement. Postsurgical MR neurography consistently coincided with clinical outcomes related to pain, sensation, and lip biting and speech challenges. Lip biting and speech challenges were most amenable to recovery, even with evidence of persistent nerve pathology on postsurgical MR neurography.

MVA-based vaccines are protective against lethal eastern equine encephalitis virus aerosol challenge in cynomolgus macaques.

MVA-based monovalent eastern equine encephalitis virus (MVA-BN-EEEV) and multivalent western, eastern, and Venezuelan equine encephalitis virus (MVA-BN-WEV) vaccines were evaluated in the cynomolgus macaque aerosol model of EEEV infection. Macaques vaccinated with two doses of 5 × 108 infectious units of the MVA-BN-EEEV or MVA-BN-WEV vaccine by the intramuscular route rapidly developed robust levels of neutralizing antibodies to EEEV that persisted at high levels until challenge at day 84 via small particle aerosol delivery with a target inhaled dose of 107 PFU of EEEV FL93-939. Robust protection was observed, with 7/8 animals receiving MVA-BN-EEEV and 100% (8/8) animals receiving MVA-BN-WEV surviving while only 2/8 mock vaccinated controls survived lethal challenge. Complete protection from viremia was afforded by both vaccines, with near complete protection from vRNA loads in tissues and any pathologic evidence of central nervous system damage. Overall, the results indicate both vaccines are effective in eliciting an immune response that is consistent with protection from aerosolized EEEV-induced disease.

Preliminary study on implementation of modified tubular gastric side-overlap anastomosis in laparoscopic proximal gastrectomy

Objective: To investigate the feasibility and safety of implementing modified tubular gastric side-overlap anastomosis in laparoscopic proximal gastrectomy. Methods: In this retrospective, descriptive case series, we analyzed clinical data of seven patients who had undergone laparoscopic proximal gastrectomy and gastrointestinal reconstruction with modified tubular gastric side-overlap anastomosis from October 2022 to March 2023 in the Second Affiliated Hospital of Fujian Medical University. The study patients comprised five men and two women aged 57-72 years and of body mass index 18.5-25.7 kg/m2. All seven patients had preoperative gastroscopic and pathological evidence of esophagogastric junction cancer and all were found by preoperative enhanced computed tomography and/or endoscopic ultrasonography to have stage CT1-2N0M0 tumors. The main steps in the reconstruction of a modified tubular gastric side-overlap anastomosis are as follows: (1) mobilizing the lower esophagus and opening the left pleura to expand the space; (2) severing the esophagus with a linear cutter stapler; (3) creating a 3-cm-wide tubular stomach along the greater curvature; (4) creating a 5-cm guide line on the lesser curvature of the anterior wall of the tubular stomach and a small opening below the guide line; (5) rotating the esophageal stump 90° counterclockwise and making a small opening on the right posterior wall of the esophageal stump, along with using a 45-mm linear cutter stapler for esophagogastric side-to-side anastomosis under the guidance of the gastric tube and guide line ; (6) closing the common opening using barbed sutures; (7) embedding the cut edge of the esophageal stump such as to closely oppose it to the esophagus; (8) using barbed sutures to continuously suture the lower esophagus bilaterally to the anterior wall of the tubular stomach; and (9) closing the opened esophageal hiatus and pleura. The main outcome measures were intraoperative (operation time, digestive tract reconstruction time, closing the common opening time, intraoperative blood loss, and number of dissected lymph nodes), postoperative (time to passage of flatus , time to liquid diet, time to ambulation, length of postoperative hospital stay, and postoperative complications), pathological (maximum diameter of the tumor and pathological stage) and findings on follow-up. Results: Laparoscopic proximal gastrectomy with reconstruction of a modified tubular gastric side-overlap anastomosis was successfully completed in all seven patients; no conversion to laparotomy was required and there were no postoperative complications. The operation time, digestive tract reconstruction time, and closing of common opening time were 187-229, 61-79, and 7-9 minutes, respectively. Intraoperative blood loss was 15-23 ml and the number of dissected lymph nodes was 14-46 per case. Time to passage of flatus, time to liquid diet, time to ambulation, and postoperative hospital stay were 1-2, 2-3, 3-4, and 6-7 days, respectively. Postoperative pathological examination showed that the maximum tumor diameters were 1.6-3.3 cm in four patients with stage IA disease and three patients with stage IB. The seven patients were followed up for 6-11 months, during which none required routine use of proton pump inhibitors or gastric mucosal protective agents and there were no deaths or tumor recurrence/metastasis. No patients had anemia or hypoproteinemia 3 and 6 months after surgery. Six months after surgery, NRS2002 and GERDQ scores were 1-2 and 2-3, respectively. Gastroscopy showed narrow anastomoses in 6 patients with Los Angeles grade A and one patient with grade B disease. No evidence of significant bile reflux was found and no anastomotic stenosis or reflux was detected on upper gastrointestinal angiography. Conclusion: It is safe and feasible to implement modified tubular gastric side-overlap anastomosis for digestive tract reconstruction in laparoscopic proximal gastrectomy.

Cell type-specific functions of Alzheimer's disease endocytic risk genes.

Endocytosis is a key cellular pathway required for the internalization of cellular nutrients, lipids and receptor-bound cargoes. It is also critical for the recycling of cellular components, cellular trafficking and membrane dynamics. The endocytic pathway has been consistently implicated in Alzheimer's disease (AD) through repeated genome-wide association studies and the existence of rare coding mutations in endocytic genes. BIN1 and PICALM are two of the most significant late-onset AD risk genes after APOE and are both key to clathrin-mediated endocytic biology. Pathological studies also demonstrate that endocytic dysfunction is an early characteristic of late-onset AD, being seen in the prodromal phase of the disease. Different cell types of the brain have specific requirements of the endocytic pathway. Neurons require efficient recycling of synaptic vesicles and microglia use the specialized form of endocytosis-phagocytosis-for their normal function. Therefore, disease-associated changes in endocytic genes will have varied impacts across different cell types, which remains to be fully explored. Given the genetic and pathological evidence for endocytic dysfunction in AD, understanding how such changes and the related cell type-specific vulnerabilities impact normal cellular function and contribute to disease is vital and could present novel therapeutic opportunities. This article is part of a discussion meeting issue 'Understanding the endo-lysosomal network in neurodegeneration'.

Increasing variance of rich-club nodes distribution in early onset depression according to dynamic network.

Early onset depression (EOD) and late onset depression (LOD) are thought to have different pathogeneses, but lack of pathological evidence. In the current study we describe the dynamic rich-club properties of patients with EOD and LOD to address this question indirectly. We recruited 82 patients with late life depression (EOD 40, LOD 42) and 90 healthy controls. Memory, executive function and processing speed were measured, and resting-stage functional MRI was performed with all participants. We constructed a dynamic functional connectivity network and carried out rich-club and modularity analyses. Normalized mutual information (NMI) was applied to describe the variance in rich-club nodes distribution and partitioning. The NMI coefficient of rich club nodes distribution among the three groups was the lowest in the EOD patients (F = 4.298; P = 0.0151, FDR = 0.0231), which was positively correlated with rich-club connectivity (R = 0.886, P < 0.001) and negatively correlated with memory (R = -0.347, P = 0.038) in the EOD group. In the LOD patients, non-rich-club connectivity was positively correlated with memory (R = 0.353, P = 0.030 and R = 0.420, P = 0.009). Furthermore, local connectivity was positively correlated with processing speed in the LOD patients (R = 0.374, P = 0.021). The modular partition was different between the EOD patients and the HCs (P = 0.0013 < 0.05/3). The temporal instability of rich-club nodes was found in the EOD patients, but not the LOD patients, supporting the hypothesis that EOD and LOD result from different pathogenesis, and showing that the instability of the rich-club nodes across time might disrupt rich-club connectivity.

The expanding role of sonography for the diagnosis of deep infiltrating endometriosis: Results of a large case series.

To investigate the value of the sonographic identification of deep infiltrating endometriosis (DIE) in women presenting with complaints suggestive of DIE. Sonography findings were correlated with subsequent surgical exploration, and histologic verification. A retrospective observational case series was investigated to document the ability of the use of sonography to accurately detect the presence of deep infiltrating endometriosis. The clinical observations were performed consistent with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) recommendations for observational studies. Recognizing the real-world office setting for this may introduce the importance of the practical clinical aspects of diagnostic procedures in general. Three-dimensional transvaginal sonography was able to accurately identify deep invasive endometriosis in 92% of the 100 women subjectively complaining of the associated symptoms of endometriosis, who underwent sonography, surgical exploration, and pathologic analysis. Additional sonographic evidence of pelvic pathology was found during the course of this investigation, perhaps complementing other means for diagnosing endometriosis. Three-dimensional transvaginal sonography is a diagnostic tool that can effectively identify deep infiltrating endometriosis, which may otherwise go undetected and untreated. These findings should encourage the use of sonography for the detection of this subtype of endometriosis.

Regional lymph node mapping in patients with penile cancer undergoing radical inguinal lymph node dissection - a retrospective cohort study.

Radical inguinal lymph node dissection (rILND) is the most available treatment to cure penile cancer (PC) with limited inguinal-confined disease. However, guidelines regarding acceptable boundaries of rILND are controversial, and consensus is lacking. The authors aimed to standardize the surgical boundaries of rILND with definite pathological evidence and explore the distribution pattern of inguinal lymph nodes (ILNs) in PC. A total of 414 PC patients from two centers who underwent rILND were enrolled. The ILN distribution was divided into seven zones anatomically for pathological examination. Student's t test and Kaplan-Meier survival analysis were used. ILNs displayed a funnel-shaped distribution with high density in superior regions. ILNs and metastatic nodes are present anywhere within the radical boundaries. Positive ILNs were mainly concentrated in zone I (51.7%) and zone II (41.3%), but there were 8.7% and 12.3% in inferior zones V and VI, respectively, and 7.1% in the deep ILNs. More importantly, a single positive ILN and first-station positive zone was detected in all seven regions. Single positive ILNs were located in zones I through VI in 40.4%, 23.6%, 6.7%, 18.0%, 4.5%, and 1.1%, respectively, and 5.6% presented deep ILN metastasis directly. The authors established a detailed ILN distribution map and displayed lymphatic drainage patterns with definite pathological evidence using a large cohort of PC patients. Single positive ILNs and first-station metastatic zones were observed in any region, even directly with deep ILN metastasis. Only rILND can ensure tumor-free resection without the omission of positive nodes.

IgLON5 deficiency produces behavioral alterations in a knockout mouse model.

Anti-IgLON5 disease is a neurological disorder characterized by autoantibodies against IgLON5 and pathological evidence of neurodegeneration. IgLON5 is a cell adhesion molecule of unknown function that is highly expressed in the brain. Our aim was to investigate the impact of IgLON5 loss-of-function in evaluating brain morphology, social behavior, and the development of symptoms observed in an IgLON5 knockout (IgLON5-KO) mouse model. The IgLON5-KO mice were generated using CRISPR-Cas9 technology. Immunohistochemistry on fixed sagittal brain sections and Western blotting brain lysates were used to confirm IgLON5 silencing and to evaluate the presence of other cell surface proteins. Two- month-old IgLON5-KO and wild-type (WT) mice underwent a comprehensive battery of behavioral tests to assess 1) locomotion, 2) memory, 3) anxiety, 4) social interaction, and 5) depressive-like behavior. Brain sections were examined for the presence of anatomical abnormalities and deposits of hyperphosphorylated tau in young adult (2-month-old) and aged (22-month-old) mice. Mice did not develop neurological symptoms reminiscent of those seen in patients with anti-IgLON5 disease. Behavioral testing revealed that 2-month-old IgLON5-KO mice showed subtle alterations in motor coordination and balance. IgLON5-KO females exhibited hyperactivity during night and day. Males were observed to have depressive-like behavior and excessive nest-building behavior. Neuropathological studies did not reveal brain morphological alterations or hyperphosphorylated tau deposits. IgLON5-KO mice showed subtle alterations in behavior and deficits in fine motor coordination but did not develop the clinical phenotype of anti-IgLON5 disease.

Use of Endodontic Procedures in Young Permanent Teeth.

Regenerative endodontic procedures (REPs) have emerged as a promising treatment option for young permanent teeth with pulp necrosis, offering the potential for tissue repair and preservation. A retrospective analysis was conducted on a cohort of 30 patients aged 8 to 16 years with pulp necrosis in young permanent teeth. The patients underwent REPs, including disinfection, triple antibiotic paste application, and a coronal barrier. Clinical and radiographic data were collected at baseline and follow-up appointments at 6, 12, and 24 months. Radiographs were analyzed for root lengthening, apical closure, and resolution of periapical lesions. The mean increase in root length after 24 months was 3.42 mm (SD ± 1.12 mm), and 90% of cases demonstrated complete apical closure. The overall success rate, defined as the absence of clinical symptoms and radiographic evidence of pathology, was 80. REPs show promising outcomes in young permanent teeth with pulp necrosis, promoting root development, and apical closure.

New information on paleopathologies in non-avian theropod dinosaurs: a case study on South American abelisaurids

Studies on pathological fossil bones have allowed improving the knowledge of physiology and ecology, and consequently the life history of extinct organisms. Among extinct vertebrates, non-avian dinosaurs have drawn attention in terms of pathological evidence, since a wide array of fossilized lesions and diseases were noticed in these ancient organisms. Here, we evaluate the pathological conditions observed in individuals of different brachyrostran (Theropoda, Abelisauridae) taxa, including Aucasaurus garridoi, Elemgasem nubilus, and Quilmesaurus curriei. For this, we use multiple methodological approaches such as histology and computed tomography, in addition to the macroscopic evaluation. The holotype of Aucasaurus shows several pathognomonic traits of a failure of the vertebral segmentation during development, causing the presence of two fused caudal vertebrae. The occurrence of this condition in Aucasaurus is the first case to be documented so far in non-tetanuran theropods. Regarding the holotype of Elemgasem, the histology of two fused vertebrae shows an intervertebral space between the centra, thus the fusion is limited to the distal rim of the articular surfaces. This pathology is here considered as spondyloarthropathy, the first evidence for a non-tetanuran theropod. The microstructural arrangement of the right tibia of Quilmesaurus shows a marked variation in a portion of the outer cortex, probably due to the presence of the radial fibrolamellar bone tissue. Although similar bone tissue is present in other extinct vertebrates and the cause of its formation is still debated, it could be a response to some kind of pathology. Among non-avian theropods, traumatic injuries are better represented than other maladies (e.g., infection, congenital or metabolic diseases, etc.). These pathologies are recovered mainly among large-sized theropods such as Abelisauridae, Allosauridae, Carcharodontosauridae, and Tyrannosauridae, and distributed principally among axial elements. Statistical tests on the distribution of injuries in these theropod clades show a strong association between taxa-pathologies, body regions-pathologies, and taxa-body regions, suggesting different life styles and behaviours may underlie the frequency of different injuries among theropod taxa.

Medically unexplained pain and suicidal ideation among US adults

BackgroundChronic pain is an established risk factor for suicide. Pain syndromes are complex to diagnose, particularly in cases with limited evidence of injury or pathology. The goal of this study is to assess whether pain of unknown origin (i.e., medically-unexplained pain, MUEP) is more strongly associated with suicide behaviors than pain with a diagnostic explanation. MethodsData comes from the National Comorbidity Survey-Replication, a nationally-representative sample of US adults. Analysis was limited to participants with a lifetime history of any type of chronic pain (n = 3421), which were categorized as having medically-explained pain (MEP, e.g., pain due to a specific health condition or resulting from an injury identified in an x-ray) or MUEP. Logistic regression, using survey procedures, was used to assess the relationship between lifetime MUEP and lifetime history of suicidal ideation and attempts. ResultsApproximately 1 in 10 (11.6 %) adults with chronic pain had MUEP. Those with MUEP reported earlier age of pain onset and more impairment due to health problems. Suicidal ideation was reported by 18.7 % of those with MEP and 28.4 % of those with MUEP. In fully-adjusted models, MUEP was associated with 1.60 times (95 % CI: 1.17–2.18) higher odds of suicidal ideation, and 1.89 (1.25–2.83) higher odds of suicide attempt, compared to MEP. LimitationsCross-sectional analysis; MUEP assessed by self-report. ConclusionsAmong adults with chronic pain, those with MUEP are more likely to report suicide behaviors. Findings illustrate a role for diagnostic and treatment processes in the relationship between pain and suicide.