Additional Etiological Factors Research Articles

Linking the reversal of gestational insulin resistance to postpartum depression.

Postpartum depression (PPD) constitutes a significant mental health disorder affecting almost one fifth of pregnancies globally. Despite extensive research, the precise etiological mechanisms underlying PPD remain elusive. However, several risk factors like genetic predisposition, hormonal fluctuations, and stress-related environmental and psychosocial triggers have been found to be implicated in its development. MAIN: Recently, an increased risk of PPD has been reported to be associated with gestational diabetes mellitus (GDM), which is characterized by the disruption of glucose metabolism, primarily attributed to the emergence of insulin resistance (IR). While IR during pregnancy seems to be an evolutionary adaptative mechanism to handle the profound metabolic alterations during pregnancy, its subsequent resolution following delivery necessitates a reconfiguration of the metabolic landscape in both peripheral tissues and the central nervous system (CNS). Considering the pivotal roles of energy metabolism, particularly glucose metabolism, in CNS functions, we propose a novel model that such pronounced changes in IR and the associated glucose metabolism seen postpartum might account for PPD development. This concept is based on the profound influences from insulin and glucose metabolism on brain functions, potentially via modulating neurotransmitter actions of dopamine and serotonin. Their sudden postpartum disruption is likely to be linked to mood changes, as observed in PPD. The detailed pathogenesis of PPD might be multifactorial and still remains to be fully elucidated. Nevertheless, our hypothesis might account in part for an additional etiological factor to PPD development. If our concept is validated, it can provide guidance for future PPD prevention, diagnosis, and intervention.

The Young: Early-Onset Colon Cancer

AbstractEarly-onset colorectal cancer (EO-CRC), characterized by diagnosis before the age of 50 years, has emerged as a significant healthcare challenge with increasing global incidence. While traditional risk factors such as family history and inherited syndromes contribute to EO-CRC, a substantial proportion of cases remain sporadic, necessitating further investigation into additional etiological factors. Molecular studies reveal heterogeneity in EO-CRC, with distinct mutational profiles compared to late-onset CRC. Clinical management presents unique considerations, including challenges in early detection and treatment strategies tailored to younger patients. Addressing EO-CRC requires a multidisciplinary approach integrating epidemiological, molecular, and clinical insights to improve prevention, diagnosis, and therapeutic outcomes. Emerging research avenues explore novel biomarkers and therapeutic targets, offering promise for advancing understanding and management of this disease in contemporary oncology practice.

Sex differences in trigeminal neuralgia: a focus on radiological and clinical characteristics

BackgroundIt is well established that trigeminal neuralgia is more prevalent in females than in males. Neurovascular compression with morphological changes of the trigeminal root represents the most recognized etiological factor. However, other factors may play a role in the framework of a multi-hit model. The primary aim of this study was to investigate sex differences in radiological and clinical characteristics of trigeminal neuralgia to better understand the multifactorial origin of this peculiar neuropathic pain condition.MethodsIn this cross-sectional study patients with a definite diagnosis of primary trigeminal neuralgia were consecutively enrolled. Each patient underwent 3T MRI with sequences dedicated to the study of neurovascular compression. Major morphological changes of the trigeminal root were quantitatively assessed. Clinical characteristics were systematically collected through a dedicated questionnaire. A logistic regression model was implemented to predict radiological and clinical characteristics based on sex.ResultsA total of 114 patients with classical (87) or idiopathic trigeminal neuralgia (27) were enrolled. Female sex was predictive for idiopathic trigeminal neuralgia. Male sex was predictive, among the comorbidities and clinical characteristics, for hypertension, the involvement of the left side and the second trigeminal division, alone or with the ophthalmic division.DiscussionThe preponderance of TN in the female sex and the association between idiopathic TN and the female sex suggest the role of additional etiological factors in the framework of a multi-hit model. The identification of clinical variables predicted by sex suggests the possibility that distinct phenotypes, with peculiar pathophysiological and therapeutic aspects, may occur in females and males.

Differential risk of 23 site-specific incident cancers and cancer-related mortality among patients with metabolic dysfunction-associated fatty liver disease: a population-based cohort study with 9.7 million Korean subjects.

Although an association between metabolic dysfunction-associated fatty liver disease (MAFLD) and cardiovascular disease or overall mortality has been reported, it is unclear whether there is an association between MAFLD and cancer incidence or mortality. We aimed to investigate the differential risk of all- and site-specific cancer incidence and mortality according to MAFLD subgroups categorized by additional etiologies of liver disease. Using the Korean National Health Insurance Service database, we stratified the participants into three groups: (1) single-etiology MAFLD (S-MAFLD) or MAFLD of pure metabolic origin; (2) mixed-etiology MAFLD (M-MAFLD) or MAFLD with additional etiological factor(s) (i.e., concomitant liver diseases and/or heavy alcohol consumption); and (3) non-MAFLD. Hepatic steatosis and fibrosis were defined using the fatty liver index and the BARD score, respectively. Cox proportional hazards regression was performed to estimate the risk of cancer events. Among the 9,718,182 participants, the prevalence of S-MAFLD and M-MAFLD was 29.2% and 6.7%, respectively. During the median 8.3 years of follow-up, 510,330 (5.3%) individuals were newly diagnosed with cancer, and 122,774 (1.3%) cancer-related deaths occurred among the entire cohort. Compared with the non-MAFLD group, the risk of all-cancer incidence and mortality was slightly higher among patients in the S-MAFLD group (incidence, adjusted hazard ratio [aHR] = 1.03; 95% confidence interval [CI]: 1.02-1.04; mortality, aHR = 1.06; 95% CI: 1.04-1.08) and highest among patients with M-MAFLD group (incidence, aHR = 1.31; 95% CI: 1.29-1.32; mortality, aHR = 1.45; 95% CI: 1.42-1.48, respectively). The M-MAFLD with fibrosis group (BARD score ≥ 2) showed the highest relative risk of all-cancer incidence (aHR = 1.38, 95% CI = 1.36-1.39), followed by the M-MAFLD without fibrosis group (aHR = 1.09, 95% CI = 1.06-1.11). Similar trends were observed for cancer-related mortality. MAFLD classification, by applying additional etiologies other than pure metabolic origin, can be used to identify a subgroup of patients with poor cancer-related outcomes.

Evaluation of the Increase in Serum Calcium Levels After Unilateral Adrenalectomy.

IntroductionThis study aims to investigate the prevalence and characteristics of patients with elevated serum calcium due to adrenal insufficiency after unilateral adrenalectomy.MethodsThe study included 76 patients who underwent unilateral adrenalectomy from January 2012 to November 2021 and did not have an additional etiologic factor for hypercalcemia, During the postoperative period, the highest calcium value in six months was taken into account as the postoperative value. Calcium values were corrected according to the albumin value.ResultsOf the 76 patients included in the study, serum calcium levels were higher in six patients (7.9%) after adrenalectomy. Unlike the others, a decrease in glomerular filtration rate (GFR) and an increase in serum creatinine values were detected in the postoperative period in this patient group. In this patient group, the corrected calcium level detected an average increase of 1.3 mg/dL.ConclusionAfter unilateral adrenalectomy, hypercalcemia may occur due to adrenal insufficiency. It should also be considered that there may be a decrease in GFR and increased creatinine in these patients.

Post-infantile Giant Cell Hepatitis: A Literature Review and Meta-analysis.

Post-infantile giant cell hepatitis (PIGCH) is a rare disease entity in adults with a multifactorial etiology and widely variable clinical courses and outcomes. The factors associated with the worse outcomes of this disease entity are still unclear. We identified 68 PIGCH patients by searching PubMed and performed meta-analysis. Among the 68 patients, 32% of the cases were associated with autoimmune disorders, followed by 21% associated with viral infections, 10% with medication, and 7% with malignancy. Twenty-four percent of the patients had more than one etiological factor, and 6% had other uncommon etiologies or an etiology that could not be identified. At the time of this report, 17 patients had died of the disease (poor outcome), and 51 patients remained alive with the disease (good outcome). Compared to the patients with a good outcome, the patients with a poor outcome were characterized by older age, lower levels of platelets and albumin, higher level of total bilirubin, and a diffuse distribution pattern of giant cells in the liver. There were no differences in gender distribution, aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, etiological distribution, or other histological features, including interface hepatitis, necrosis, lobular inflammation, portal inflammation, cholestasis, or fibrosis. Further studies would be needed to better understand the disease mechanisms and unmask any additional etiological factors and targeted therapies.

CHANGES IN QUALITY OF LIFE AND EXPRESSION OF ANXIETY AND DEPRESSION IN PATIENTS WITH DIVERTICULAR COLON DISEASE

The constant increase in the incidence of diverticular disease (DD), especially in middle-aged and elderly people, the establishment of new additional etiological factors of development and pathogenetic mechanisms of progression make the problem of this nosology extremely relevant. The presence of persistent symptoms such as abdominal pain, stool disorders, which constantly bother 20% of patients and frequent recurrences of diverticulitis and their complications, which occur in 25% of such patients, lead to high levels of stress. Diverticular disease has a negative impact on the quality of life of patients, which worsens with increasing duration of the disease. Most studies on quality of life and the development of anxiety and depression concern patients with complicated diverticular disease and patients after surgery for their complications. At the same time, there is limited information and statistics on the relationship between uncomplicated diverticular disease and anxiety, depression and reduced quality of life.
 The aim of the study: to assess the severity of anxiety and depression and reduced quality of life in patients with diverticular disease of the colon.
 Materials and methods. The study included 48 patients with diverticular disease, 32 - with irritable bowel syndrome and 15 healthy individuals. Depending on the severity of clinical manifestations, the nature of the course, the results of laboratory, radiological, sonographic results and computed tomography used classification of DD according to B. Lembske, and among patients such types as 0, 3a, 3b prevailed, which was 87.5 %. Taylor scales, the Hospital Anxiety and Depression Scale (HADS), and the Spielberg-Hanin situational anxiety level were used to assess the severity of anxiety and depression. The quality of life of patients and patients in the control group was assessed using the GIQLI questionnaire and the WSAS questionnaire (appendices A and D).
 Research results. According to the Taylor scale, a high level of anxiety (35.8 ± 0.8 points) occurred in 58.3%, and average (23.9 ± 0.7 points) in 22.9% of respondents, while in healthy people the indicator was low (12.0 ± 1.1 points). In 20.8% of patients with diverticular disease, symptoms of depression prevailed with an index of 12.2 ± 1.1 points. According to the results of the Spielberg-Hanin questionnaire, 72.9% of patients with DD had moderate anxiety (39.7 ± 1.2 points), and 20.1% had depression (6.7 ± 1.0 points). There is a direct correlation between anxiety indicators according to the Taylor, Spielberg - Khanin scale (r = 0.71 p <0.05).
 The quality of life of patients with DH decreased by 30.2% due to intestinal symptoms and slightly less due to the emotional component. Diverticular disease decreased physical status (by 18.7 points) and social activity (by 9.3 points). Appendix D of the WSAS also confirmed a decline in employment and social activity and a quality of life (Appendix A).
 Conclusions. Thus, uncomplicated diverticular disease causes anxiety in 81.2%, and depression - in 20.8%, and according to Spielberg - Khanin - in 72.9% and 20.1%, respectively. Diverticular disease also reduces the quality of life according to the GIQLI questionnaire by 37.64%. Assessment of manifestations of anxiety and depression and reduced quality of life will allow to choose further tactics of treatment of patients with diverticular disease.

(Post) Covid-19 Panniculitis

In its essence, panniculitis is the presence of an inflammatory infiltrate in the subcutaneous adipose tissue. Paniculitis as a clinical diagnosis encompasses a group of diseases that creates difficulties for both clinicians - dermatologists and histopathologists, mainly due to the many known forms of the disease, but also due to the various etiological reasons for their occurrence. Therefore, the clinical-pathological correlation plays an important role in the diagnosis. The development of various forms of panniculitis, in particular eosinophilic and generalized lymphocytic, have been described after Covid-19 infection.In the case of our patient, the development of panniculitis was observed after Covid-19 pneumonia. However, as additional etiological factors should be considered 1) the accompanying chronic diseases of the patient - congestive heart failure, hypertension and type 2 diabetes mellitus, which may also be etiological factors for the appearance of a certain form of panniculitis - stasis dermatitis / lipodermatosclerosis, 2) as well as the presence of probable bladder cancer - possible paraneoplastic genesis, 3) and the intake of enoxaparine - drug-induced panniculitis. Given the multifactorial genesis of panniculitis, the past infection with Covid-19, in our case, can be considered as a major trigger of the disease, which developed in the background of several etiological factors. For these reasons, our patient can also be diagnosed with post-Covid-19 panniculitis. Keywords: Lobular Panniculitis; Septal Panniculitis; Covid-19; Stasis Dermatitis; Corticosteroids; Paraneoplastic Reaction; Drug Induced Panniculitis

A Case of Abducens Nerve Palsy Caused by Sinusitis Indistinguishable from Diabetic Ophthalmoplegia

[Introduction] Cranial nerve palsies can occur as a complication of several diseases, such as diabetes mellitus, aneurysm, and sinusitis. We have encountered many cases in which we successfully identified the cause of the cranial nerve palsy, but later also found an additional etiologic factor. Thus, even in a patient with sinusitis developing a cranial nerve palsy, the palsy could be caused by a disease other than sinusitis.

Eradication of Helicobacter pylori and Gastric Cancer: A Controversial Relationship.

Worldwide, gastric cancer (GC) represents the fifth cancer for incidence, and the third as cause of death in developed countries. Indeed, it resulted in more than 780,000 deaths in 2018. Helicobacter pylori appears to be responsible for the majority of these cancers. On the basis of recent studies, and either alone or combined with additional etiological factors, H. pylori is considered a “type I carcinogen.” Over recent decades, new insights have been obtained into the strategies that have been adopted by H. pylori to survive the acidic conditions of the gastric environment, and to result in persistent infection, and dysregulation of host functions. The multistep processes involved in the development of GC are initiated by transition of the mucosa into chronic non-atrophic gastritis, which is primarily triggered by infection with H. pylori. This gastritis then progresses into atrophic gastritis and intestinal metaplasia, and then to dysplasia, and following Correa’s cascade, to adenocarcinoma. The use of antibiotics for eradication of H. pylori can reduce the incidence of precancerous lesions only in the early stages of gastric carcinogenesis. Here, we first survey the etiology and risk factors of GC, and then we analyze the mechanisms underlying tumorigenesis induced by H. pylori, focusing attention on virulence factor CagA, inflammation, oxidative stress, and ErbB2 receptor tyrosine kinase. Moreover, we investigate the relationships between H. pylori eradication therapy and other diseases, considering not only cardia (upper stomach) cancers and Barrett’s esophagus, but also asthma and allergies, through discussion of the “hygiene hypothesis. ” This hypothesis suggests that improved hygiene and antibiotic use in early life reduces microbial exposure, such that the immune response does not become primed, and individuals are not protected against atopic disorders, asthma, and autoimmune diseases. Finally, we overview recent advances to uncover the complex interplay between H. pylori and the gut microbiota during gastric carcinogenesis, as characterized by reduced bacterial diversity and increased microbial dysbiosis. Indeed, it is of particular importance to identify the bacterial taxa of the stomach that might predict the outcome of gastric disease through the stages of Correa’s cascade, to improve prevention and therapy of gastric carcinoma.

The histopathology of SPINK1-associated chronic pancreatitis

BackgroundThe identification of genetic risk factors for chronic pancreatitis, such as PRSS1, CFTR and SPINK1, provides the opportunity to define key pathologic hallmarks and etiologic-specific changes. For example, pancreata from PRSS1 and CFTR patients exhibit progressive lipomatous atrophy without significant fibrosis. Considering the pathology of SPINK1-associated pancreatitis is ill-defined, we examined the pancreata of SPINK1 patients with chronic pancreatitis. MethodsHistologic sections after total pancreatectomy with islet autotransplantation and associated clinicopathologic data were collected from 28 patients with SPINK1 germline alterations. Clinical findings, germline data, anatomic anomalies and pathologic findings were descriptively evaluated. ResultsPatients ranged in age from 5 to 48 years (median, 21.6 years) with abdominal pain between 2 and 25 years (median, 5.8 years). Most patients were SPINK1 heterozygous and 14 (50%) had co-occurring CFTR (n = 12) and CTRC (n = 2) mutations. Other pancreatitis risk factors included anatomic anomalies (n = 9) and tobacco use (n = 1). Overall, 24 (86%) patients had additional pancreatitis-associated germline alterations, SPINK1 homozygosity, anatomic anomalies or environmental factors. Examination of pancreata revealed a sequential pattern of exocrine parenchymal loss and replacement by prominent fibrosis, dependent on the duration of abdominal pain. No malignancies were identified, but low-grade pancreatic intraepithelial neoplasia was present for 2 cases. ConclusionsWithin this descriptive study, SPINK1-associated pancreatitis is characterized by parenchymal fibrosis and suggests divergent pathophysiologic mechanisms from PRSS1 and CFTR-associated pancreatitis. Moreover, SPINK1 patients frequently had additional etiologic factors that did not impact the development of pancreatic fibrosis and may implicate SPINK1 as a disease modifier gene.

Characterization of the interactions between Codanin-1 and C15Orf41, two proteins implicated in congenital dyserythropoietic anemia type I disease

BackgroundCongenital dyserythropoietic anemia type I (CDA I), is an autosomal recessive disease with macrocytic anemia in which erythroid precursors in the bone marrow exhibit pathognomonic abnormalities including spongy heterochromatin and chromatin bridges. We have shown previously that the gene mutated in CDA I encodes Codanin-1, a ubiquitously expressed and evolutionarily conserved large protein. Recently, an additional etiologic factor for CDA I was reported, C15Orf41, a predicted nuclease. Mutations in both CDAN1 and C15Orf41 genes results in very similar erythroid phenotype. However, the possible relationships between these two etiologic factors is not clear.ResultsWe demonstrate here that Codanin-1 and C15Orf41 bind to each other, and that Codanin-1 stabilizes C15Orf41. C15Orf41 protein is mainly nuclear and Codanin-1 overexpression shifts it to the cytoplasm. Phylogenetic analyses demonstrated that even though Codanin-1 is an essential protein in mammals, it was lost from several diverse and unrelated animal taxa. Interestingly, C15Orf41 was eliminated in the exact same animal taxa. This is an extreme case of the Phylogenetic Profiling phenomenon, which strongly suggests common pathways for these two proteins. Lastly, as the 3D structure is more conserved through evolution than the protein sequence, we have used the Phyre2 alignment program to find structurally homologous proteins. We found that Codanin-1 is highly similar to CNOT1, a conserved protein which serves as a scaffold for proteins involved in mRNA stability and transcriptional control.ConclusionsThe physical interaction and the stabilization of C15Orf41 by Codanin-1, combined with the phylogenetic co-existence and co-loss of these two proteins during evolution, suggest that the major function of the presumptive scaffold protein, Codanin-1, is to regulate C15Orf41 activities. The similarity between Codanin-1 and CNOT1 suggest that Codanin-1 is involved in RNA metabolism and activity, and opens up a new avenue for the study of the molecular pathways affected in CDAI.

Human Papillomavirus and Factors Associated with Recurrence in Sinonasal Inverted Papillomas from Poland and Spain.

Sinonasal inverted papilloma (SNIP) is a benign but locally aggressive tumor that has a tendency for recurrence and malignant transformation. The role of human papillomavirus (HPV) in SNIP is controversial. To determine the HPV-DNA prevalence and type distribution in SNIP in two different geographic areas and assess the association between SNIP recurrence and HPV infection, as well as additional potential etiologic factors. Two retrospective cohorts of SNIP patients from Poland and Spain were evaluated. Demographic, tobacco/alcohol use, clinical, and follow-up data were collected. All samples were subject to histopathologic evaluation, DNA quality control, and HPV-DNA detection by PCR. HPV-DNA positive samples and a random sample of HPV-DNA negative cases were further subject to p16INK4a analysis. Proportional-hazards models were used to evaluate the risk of recurrence by selected variables. Seventy-nine SNIP patients (46 from Spain diagnosed between 1995 and 2014, and 33 from Poland diagnosed between 2012 and 2017) were included in the study. HPV-DNA was detected in four patients (5.1%), two from each region, and all four were positive for the HPV11 subtype. Seventeen patients (21.5%) experienced recurrence, with a median time to recurrence of 14months. No association was identified between lesional HPV-DNA positivity, toxic habits, Krouse stage, or malignant transformation and a higher risk of recurrence. The low prevalence of HPV-DNA in SNIPs suggests that HPV is not a main etiology for development of these lesions. With a lack of association between the evaluated factors and recurrence, further research with larger number of patients and additional biomarkers is warranted to further understand predisposing risk factors.

Hormone receptor expression of colorectal cancer diagnosed during the peri-partum period.

BackgroundColorectal carcinoma (CRC) during the peri-partum period is challenging to diagnose due to the overlapping symptoms of CRC and pregnancy. This is the first case series to investigate clinicopathologic, hormonal and molecular features of CRC diagnosed during the peri-partum period. We hypothesized that advanced presentations of CRC could possibly be mitigated by pregnancy-related hormonal factors.MethodsWe conducted a retrospective review of five women diagnosed with CRC during the peri-partum period and studied the clinical and molecular features of their cancer.ResultsAll patients presented with stage IV CRC at diagnosis; three had primary tumors in the rectum and two had primary tumors in the sigmoid colon. The liver was the most common metastatic site (three of five women). Immunohistochemistry stains were negative for estrogen receptors alpha (ERα) and beta (ERβ), and one tumor demonstrated low-level positivity for PR (1%). Formalin-fixed and paraffin-embedded (FFPE) biopsies from each case were tested with next-generation sequencing and found that all tumors were mismatch repair (MMR) proficient, and three harbored a KRAS mutation. Germline testing showed no predisposition to CRC; however, several somatic variants of undetermined significance (VUS) were identified.DiscussionCRC in the peri-partum period poses significant risk factors for presentations with advanced disease due to diagnostic challenges. While our study provides no evidence that pathogenesis of CRC during pregnancy is driven by elevated estrogen and/or progesterone levels during pregnancy, additional putative etiologic factors, including placental growth factors, the immunosuppressive state of pregnancy and other physiologic processes during pregnancy, warrant future study.

Lack of association between denture trauma and loss of heterozygosity confronts the proposed pathologic role of chronic mucosal trauma in oral carcinogenesis.

Chronic mucosal trauma is suggested as an additional etiologic risk factor for oral squamous cell carcinoma (OSCC), but there is a lack of experimental-molecular data. If chronic trauma of the oral mucosa is carcinogenic, it should be associated with early genetic alterations seen during typical progression of OSCC, like loss of heterozygosity (LOH). We investigated LOH in the key chromosomal arms 3p, 9p and 17p in inflammatory fibrous hyperplasia associated with removable dental prosthesis and also in normal oral mucosa, by using the polymorphic microsatellite markers D3S1300 at 3p14.2, D9S1748 at 9p21, D17S1289 at 17p12 and D17S974 at 17p13 and capillary electrophoresis. LOH was detected in 2/15 (13%) fibrous hyperplasia samples similarly to other reactive and inflammatory lesions. None of the normal mucosa samples presented LOH. Our experimental-molecular results do not support the hypothesis that trauma associated with dental prosthesis has an important role in oral carcinogenesis.

Моlecular mechanisms of initiation of carcinogenesis in the testis.

In this review, literature data on the study of precancerous changes in testicular tissue and molecular changes, as well as the influence of environmental factors that can initiate carcinogenesis, were analyzed and summarized for the future determination of early diagnosis of germ cell tumors of the testis and the development of preventive measures. The review also discusses the significant new changes presented in the Fourth Edition of the World Health Organization Classification of Urogenital Tumors, published in2016, and modern concepts of the etiology and pathogenesis of these diseases. Among the environmental factors that can initiate carcinogenesis, the most noteworthy are the biological effects of low doses of ionizing radiation, such as the effect of radiation-induced genome instability, which increases the risk of carcinogenesis, the "bystander effect", and chronic oxidative stress. Disruption of ubiquitin-proteasomal proteolysis, impaired molecular-level components of the blood-testis barrier, and impaired regulatory action of TGF-β on the cell cycle can play a crucial role in the pathogenesis of male infertility and the initiation of carcinogenesis in the testis. The effect of low doses of ionizing radiation as an additional etiological factor leads to changes in the structural, as well as molecular, components of the testis, including epigenetic changes, which can be characterized as environmental pathomorphosis, which leads to impaired spermatogenesis and increased risk of malignancy. Summarizing the literature review data, we can state that patients with blocked spermatogenesis, in which atypical germ cell neoplasia in situ cells are detected in testicular tissue, constitute a group at increased risk of testicular carcinogenesis. The presence of additional etiological factors, such as chronic low doses of ionizing radiation, can initiate the progression of carcinogenesis in the testicle.

Prevalence and Associations of Avascular Necrosis of the Hip in a Large Well-characterized Cohort of Patients With Inflammatory Bowel Disease.

Avascular necrosis (AVN) is associated with significant morbidity potentially causing severe pain and disability; patients with inflammatory bowel disease (IBD) have a higher prevalence of AVN compared with non-IBD populations. The purpose of our study was to determine the prevalence of AVN in our IBD population and to evaluate these subjects for the presence of clinical characteristics associated with AVN on computed tomography (CT) imaging. In 1313 IBD patients with abdomen/pelvis CT scans, we identified 27 patients (2.1%) with CT findings consistent with AVN. Through historical chart review, we confirmed that most patients had prior exposure to steroids, although 2 patients had no documented steroid exposure at all. We found that 59% of the concurrent radiology reports did not comment on the presence of AVN, suggesting that incidental CT findings of AVN among IBD patients are likely underreported. Notably, we found that 63% of these cases had documented complaints of low-back and/or hip pain. Using logistic regression, we found an association between anti-neutrophil cytoplasmic antibody-positive status across IBD (p = 0.007) and a smoking history in Crohn disease (p = 0.03) with the presence of AVN. We found that a significant proportion of IBD patients with AVN are reported in their records as having hip or low-back pain, and review of CT imaging under dedicated bone windows may identify AVN among this population. Our findings also suggest that additional etiological factors, beyond corticosteroids, contribute to the development of AVN in IBD. Further investigation is warranted regarding the mechanisms associated with AVN in IBD.

Psychosis Beyond the 22q11.2 Deletion: Do Additional Genetic Factors Play a Role?

Psychosis Beyond the 22q11.2 Deletion: Do Additional Genetic Factors Play a Role?

Infection with purified Piscine orthoreovirus demonstrates a causal relationship with heart and skeletal muscle inflammation in Atlantic salmon

Viral diseases pose a significant threat to the productivity in aquaculture. Heart- and skeletal muscle inflammation (HSMI) is an emerging disease in Atlantic salmon (Salmo salar) farming. HSMI is associated with Piscine orthoreovirus (PRV) infection, but PRV is ubiquitous in farmed Atlantic salmon and thus present also in apparently healthy individuals. This has brought speculations if additional etiological factors are required, and experiments focusing on the causal relationship between PRV and HSMI are highly warranted. A major bottleneck in PRV research has been the lack of cell lines that allow propagation of the virus. To bypass this, we propagated PRV in salmon, bled the fish at the peak of the infection, and purified virus particles from blood cells. Electron microscopy, western blot and high-throughput sequencing all verified the purity of the viral particles. Purified PRV particles were inoculated into naïve Atlantic salmon. The purified virus replicated in inoculated fish, spread to naïve cohabitants, and induced histopathological changes consistent with HSMI. PRV specific staining was demonstrated in the pathological lesions. A dose-dependent response was observed; a high dose of virus gave earlier peak of the viral load and development of histopathological changes compared to a lower dose, but no difference in the severity of the disease. The experiment demonstrated that PRV can be purified from blood cells, and that PRV is the etiological agent of HSMI in Atlantic salmon.

Large-Sized Bilateral Atherosclerotic Axillary Artery Aneurysms: A Case Report.

Axillary artery aneurysms are most commonly caused by trauma, while atraumatic cases are very rare. Atherosclerosis, collagen tissue diseases, and mycotic infections are additional etiological factors for this type of aneurysms. Once developed, an aneurysm poses risk for hand ischemia or neurologic complications due to embolic events and neural compression. Due to this, diagnosis and treatment of an aneurysm are crucial. We report a case of giant bilateral axillary artery aneurysms developed as a consequence of atherosclerosis.