Viral Infections, Are They a Trigger and Risk Factor of Alzheimer's Disease?

Alzheimer's Disease (AD), a progressive and debilitating condition, is reported to be the most common type of dementia, with at least 55 million people believed to be currently affected. Many causation hypotheses of AD exist, yet the intriguing link between viral infection and its possible contribution to the known etiology of AD has become an attractive focal point of research for the field and a challenging study task. In this review, we will explore the historical perspective and milestones that led the field to investigate the viral connection to AD. Specifically, several viruses such as Herpes Simplex Virus 1 (HSV-1), Zika virus (ZIKV), and severe cute respiratory syndrome coronavirus 2 (SARS-CoV-2), along with several others mentioned, include the various viruses presently considered within the field. We delve into the strong evidence implicating these viruses in the development of AD such as the lytic replication and axonal transport of HSV-1, the various mechanisms of ZIKV neurotropism through the human protein Musashi-1 (MSI1), and the spread of SARS-CoV-2 through the transfer of the virus through the BBB endothelial cells to glial cells and then to neurons via transsynaptic transfer. We will also explore beyond these mere associations by carefully analyzing the potential mechanisms by which these viruses may contribute to AD pathology. This includes but is not limited to direct neuronal infections, the dysregulation of immune responses, and the impact on protein processing (Aß42 and hyperphosphorylated tau). Controversies and challenges of the virus-AD relationship emerge as we tease out these potential mechanisms. Looking forward, we emphasize future directions, such as distinct questions and proposed experimentations to explore, that the field should take to tackle the remaining unanswered questions and the glaring research gaps that persist. Overall, this review aims to provide a comprehensive survey of the past, present, and future of the potential link between viral infections and their association with AD development while encouraging further discussion.

Virtual reality exergames for improving physical function, cognition and depression among older nursing home residents: A systematic review and meta-analysis.

OBJECTIVE: To explore the effectiveness of virtual reality (VR) exergames on physical function, cognition and depression among older nursing home residents. METHODS: A systematic review and meta-analysis were conducted. The PubMed, Ovid, Embase, Cochrane, CINAHL, and Web of Science databases were searched for relevant studies from inception until June 1, 2023. The reviewers independently completed the study selection, data extraction and quality assessment. Subgroup analyses were conducted to explore the sources of between-study heterogeneity and to determine whether participant or intervention characteristics influenced effect sizes. RESULTS: Eighteen studies met the inclusion criteria and were selected for qualitative and quantitative synthesis. The overall methodological quality was relatively high, and the overall evidence grade was moderate. VR exergames had a large effect on physical function, including mobility [SMD=-0.66, P < 0.001], balance [SMD=0.95, P < 0.001], and lower limb strength [SMD=0.53, P = 0.0009]; and a moderate effect on cognition [SMD=0.48, P = 0.02] and depression [SMD=-0.72, P = 0.03]. Subgroup analyses revealed that a training frequency of 2 sessions per week and coordinating with physiotherapists yielded greater improvements in mobility (P = 0.009; P = 0.0001). VR exergames had especially beneficial effects on balance for physically fit participants (P = 0.03) and on cognition for participants with cognitive impairment (P = 0.01). Additionally, regarding the improvement of depression, commercial VR exergames were superior to self-made systems (P = 0.03). CONCLUSION: VR exergames can provide a positive impact on physical function, cognition and depression among older nursing home residents. The study also demonstrated the different benefits of exergames between participants who were physically fit and those with cognitive impairment, which is considered as an innovative, cost-efficient and sustainable approach. Specifically, commercial VR exergame programs with a frequency of 2 sessions per week and coordinating with physiotherapists may be the most appropriate and effective option.

DNA variants detected in primary and metastatic lung adenocarcinoma: a case report and review of the literature.

Non-small cell lung cancer (NSCLC) has been found to have recurrent genetic abnormalities, and novel therapies targeting these aberrations have improved patient survival. In this study, specimens from benign tissue, primary tumors, and brain metastases were obtained at autopsy from a 55-year-old White female patient diagnosed with NSCLC and were examined using next-generation sequencing (NGS) and chromosomal microarray assay (CMA). No genetic aberrations were noted in the benign tissue; however, NGS identified a mutation in the KRAS proto-oncogene, GTPase (KRAS): KRAS exon 2 p.G12D in primary and metastatic tumor specimens. We observed 7 DNA copy number aberrations (CNAs) in primary and metastatic tumor specimens; an additional 7 CNAs were exclusively detected in the metastatic tumor specimens. These DNA alterations may be genetic drivers in the pathogenesis of the tumor specimen from our patient and may serve as biomarkers for the classification and prognosis of NSCLC.

Hippocampal Subregions Volume and Texture for the Diagnosis of Mild Cognitive Impairment.

The aim was to examine the diagnostic efficacy of hippocampal subregions volume and texture in differentiating amnestic mild cognitive impairment (MCI) from normal aging changes. Ninety MCI subjects and eighty-eight well-matched healthy controls (HCs) were selected. Twelve hippocampal subregions volume and texture features were extracted using Freesurfer and MaZda based on T1 weighted MRI. Then, two-sample t-test and Least Absolute Shrinkage and Selection Operator (LASSO) regression were developed to select a subset of the original features. Support vector machine (SVM) was used to perform the classification task and the area under the curve (AUC), sensitivity, specificity and accuracy were calculated to evaluate the diagnostic efficacy of the model. The volume features with high discriminative power were mainly located in the bilateral CA1 and CA4, while texture feature were gray-level non-uniformity, run length non-uniformity and fraction. Our model based on hippocampal subregions volume and texture features achieved better classification performance with an AUC of 0.90. The volume and texture of hippocampal subregions can be utilized for the diagnosis of MCI. Moreover, we found that the features that contributed most to the model were mainly textural features, followed by volume. These results may guide future studies using structural scans to classify patients with MCI.

Digynic monoandric triploidy in the setting of recurrent pregnancy loss: a case report and literature review.

Triploidy is a genetic occurrence in which the chromosome count is 3n = 69 with a double (2n) chromosomal contribution to the conceptus from one parent. Such pregnancies are usually nonviable and are estimated to account for approximately 1% of recognized conceptions and 10% of recognized miscarriages. Majority opinion is that fetal losses due to triploidies are caused by the presence of 2 copies of paternal chromosomes. In this study, we present a digynic monoandric triploid miscarriage from a 32-year-old G7P1051 at approximately 13 weeks gestation, in which 2 copies of the maternal chromosomes are present in the fetus. This unusual phenomenon is supported by nonmolar placental histology, chromosomal microarray, and short tandem repeat assays, with the latter 2 being discussed in detail. Furthermore, this study includes discussion of recurrent miscarriage, recurrent triploidy, and long-term clinical follow-up of the patient.

Combined bisalbuminemia and Bisalbuminuria: A rare finding on serum and urine electrophoresis.

BACKGROUND: Bisalbuminemia and bisalbuminuria are rarely encountered serum and urine albumin anomalies characterized by the presence of a bifid albumin band on serum/urine protein electrophoresis (SPE/UPE) and serum/urine immunofixation electrophoresis (SIFE/UIFE). They are usually detected incidentally while screening for monoclonal gammopathy with a cumulative frequency of 1:1,000---1:10,000. CASE REPORT: We report two cases of bisalbuminemia in two adult male diabetic patients. The first patient had a history of rheumatoid arthritis and strong clinical suspicion for Sjogren syndrome. The SPEP/UPEP and SIFE/UIFE in this patient showed combined bisalbuminemia and bisalbuminuria. While the second patient had chronic kidney disease due to nephrotic syndrome but showed bisalbuminemia alone. CONCLUSION: Bisalbuminemia and bisalbuminuria are rare findings with few case reports available in the English literature. These findings may occur secondary to inherited albumin variants or may be acquired. Diabetes mellitus is the medical condition most associated with acquired bisalbuminemia and bisalbuminuria. Although most cases of bisalbuminemia and bisalbuminuria are clinically insignificant, some albumin variants may have altered affinity for steroid hormones (e.g., thyroxine) and/or drugs which potentially could be clinically significant.

Impacts of obesity on global subclinical left cardiac function represented by CMR-derived myocardial strain, TyG index may be a predictor.

Obesity is a recognized risk factor for heart failure. People with similar weights may have different metabolic health. Notably, insulin resistance is a hallmark of obesity and a feature of heart failure. We aimed to evaluate the effects of obesity and metabolic health status on subclinical left cardiac function. We also investigated whether insulin resistance (TyG index) plays a role in BMI-linked subclinical left cardiac dysfunction. The study involved 403 volunteers. Hierarchical multiple regression models were used to assess associations between obesity, metabolic health, and overall subclinical left cardiac function. Mediating analysis was used to explore the role of the TyG index in the association between BMI and left cardiac function. Finally, ROC analysis was performed to explore the predictive value of the TyG index in subclinical left cardiac dysfunction. The correlation analysis showed that metabolic unhealth increased the risk of subclinical left ventricular (LV) dysfunction; obesity was associated with an increased risk of global left cardiac dysfunction regardless of metabolic health status. The TyG index mediated 25% of the associations between BMI and Left atrial (LA) functional parameters. ROC analysis exhibited that the TyG index can be used as a predictor of LA dysfunction (AUC = 0.63), and the optimal cut-off point for the TyG index is 9.33. Even a "non-obese metabolically unhealthy" is a detrimental state of early LV function; obesity remains a major risk factor for global subclinical left cardiac dysfunction. Using the TyG index could allow early identification of individuals at high risk of subclinical left cardiac dysfunction.Registration number: ChiCTR2200057991; Date of registration: 2022-03-25. URL: http://www.chictr.org.cn/showproj.aspx?proj=162316 .

Investigation of lacrimal sac space-occupying lesions using color doppler ultrasound, computed tomography, and computed tomography dacryocystography.

AIM: To observe the imaging features of color Doppler ultrasound (CDU) and computed tomography (CT) or computed tomography dacryocystography (CT-DCG) in different types of lacrimal sac space-occupying lesions (SOLs). METHODS: This retrospective case series study included 21 patients with lacrimal sac SOLs who underwent lacrimal sac surgery between January 2018 and March 2022. The imaging features of CDU and CT or CT-DCG in these patients were extracted from the examination cloud system. The images were observed and analyzed. RESULTS: The detection rate of lacrimal SOLs between CDU (21/21, 100%) and CT or CT-DCG (20/21, 95.2%) had no statistically significant difference (P=1.0). CDU could detect the blood flow signals in all SOLs except mucocele and mucopeptide concretion. Among them, polyps had characteristic imaging changes on CDU and CT-DCG. The mucoceles and mucopeptide concretions had characteristic imaging changes on CDU, which could provide more information for differential diagnosis. CONCLUSION: The morphology and internal blood flow signals of lacrimal sac SOLs can be observed using CDU. CT or CT-DCG has advantages in observing structural damage around the lacrimal sac mass. Therefore, CDU may be used as a routine examination to exclude lacrimal sac SOLs before dacryocystorhinostomy in the absence of preoperative CT or CT-DCG.

Variability of Clinical Presentation in Patients Heterozygous for the F508del Cystic Fibrosis Variant: A Series of Three Cases and a Review of the Literature.

Cystic fibrosis (CF) is a genetic disease that affects the lung, pancreas, and other organs caused by the presence of biallelic CF-causing variants in the cystic fibrosis conductance regular gene (CFTR). CFTR variants can also be found in CFTR-related disorders (CFTR-RD), which present milder symptoms. Increasing access to next-generation sequencing has demonstrated that both CF and CFTR-RD have a broader array of genotypes than formerly thought. Here we present three patients who carry the most common CFTR pathogenic variant - F508del - but express a wide array of phenotypes. These cases open discussion on the role of concurrent variants in CFTR, the importance of early diagnosis and treatment, and the contribution of lifestyle factors in CF and CFTR-RD presentation.

Necrotizing plasma cell-rich aortitis and sudden cardiac death: Late sequelae of COVID-19?

The ongoing epidemic caused by the coronavirus SARS-CoV-2 is characterized by a variety of pathologic processes within the syndrome of COVID-19. Usually beginning as an upper respiratory infection with potential progression to a pneumonitis, many cases of COVID-19 that show minimal signs or symptoms initially may develop adverse systemic sequelae later, such as widespread thrombo-embolic phenomena, systemic inflammatory disorders (especially in children), or vasculitis. Here, we present a patient who suffered a sudden cardiac death following persistent SARS-CoV-2 viral positivity for four-and-one-half months after a mild clinical viral course. At routine autopsy, a remarkable plasma cell-rich necrotizing aortitis was uncovered. The aortic intima displayed diffuse, circumferential ongoing chronic intimal edema, inflammation, and neo-vascularization. The plasma cell-rich inflammatory process also involved the origin of the left main coronary artery (LM) causing a coronary arteritis accompanied by subacute, stenosing intimal vascular smooth muscle cell (VSMC) proliferation resulting in acute myocardial necrosis as a cause of death. A similar vasculitis and plaque were noted during the routine autopsy at the ostium of the celiac artery; vasculitis was not found systemically or in smaller caliber vessels. Through a variety of techniques including extensive histopathologic and immunohistochemical characterization, immunostaining localization of viral antigen, and transmission electron microscopy we present highly suggestive evidence that this unique necrotizing, plasma cell-rich aortitis is a rare sequela of COVID-19.

The first reported case of double trisomy 10 and 20 in a product of conception.

BACKGROUND: Double trisomies are rare findings among products of conception and are often lethal to the developing embryo or fetus. METHODS: Here we describe a double trisomy case with symptoms of threatened miscarriage at 9 weeks gestation. Ultrasound revealed an anembryonic pregnancy. Pregnancy was terminated by dilation and curettage at gestational age 11 weeks and 6 days. Histologic examination and chromosome microarray were performed on a formalin-fixed product of conception (POC) sample to identify the cause of the anembryonic pregnancy. RESULTS: Chromosome microarray analysis revealed a female chromosome complement with double trisomies 10 and 20, arr(10,20)x3, consistent with a karyotype of 48,XX,+10,+20. CONCLUSION: To the best of our knowledge, this is the first reported case of double trisomy 10 and 20 in a POC. Due to nonspecific histopathological findings, chromosomal microarray is a powerful tool in identifying and differentiating chromosomal aneuploidies.

Homozygous Carriers of F2 c.20210G>A Variant: A Report of Two Cases and Literature Review.

Thromboembolism is known to be a multifactorial event that is impacted by various genetic and environmental factors. The genetics society's recommended name for this variant is c.*97G>A (this is the nomenclature we need to use in the patient report). However, people have been using legacy names c.20210G>A or G20210A (so these are common names). One of the most common genetic variants associated with inherited thrombophilias, F2 c.20210G>A is acknowledged to be a weak but significant risk factor for thromboembolism. However, its clinical presentation has been described as phenotypically heterogeneous. We present two rare cases with homozygous F2 c.20210G>A variant, one of which also carries a heterozygous variant in coagulation factor V gene F5, c.1601G>A (p.Arg534Gln; commonly known as factor V Leiden). We described the clinical courses of these two cases and discussed F2 c.20210G>A and factor V Leiden as genetic risk factors in thromboembolism, the role of provoking factors, such as surgery and malignancy, and the management of such patients.

Circulating Proteins and Metabolite Biomarkers in Gastric Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: Gastric cancer (GC) is often diagnosed at an advanced stage and thus patients have a poor prognosis. This implies that early detection of this cancer will improve patient prognosis and survival. This systematic review explored the association of circulating protein and metabolite biomarkers with GC development. METHODS: A literature search was conducted until November 2021 on Medline, Embase, Cochrane library, and Web of Science databases. Studies were included if they assessed circulating proteins and metabolites in blood, urine, or saliva and determined their association with GC risk. Quality of identified studies was determined using the Newcastle-Ottawa scale for cohort studies. Random and fixed effects meta-analyses were performed to calculate pooled odds ratio. RESULTS: A total of 53 studies were included. High levels of anti-Helicobacter pylORi IgG levels, pepsinogen I (PGI) <30 µg/L and serum pepsinogen I/ pepsinogen II (PGI/II) ratio<3 were positively associated with risk of developing GC (pooled odds ratio (OR): 2.70; 95% CI: 1.44-5.04, 5.96, 95% CI: 2.65-13.42 and 4.43; 95% CI: 3.04-6.47). In addition, an inverse relationship was found between ferritin, iron and transferrin levels and risk of developing GC (OR: 0.62; 95% CI: 0.38-1,0.97; 95% CI: 0.94-1 and 0.85; 95% CI: 0.76-0.94). However, there was no association between levels of glucose, cholesterol, vitamin C, vitamin B12, vitamin A, α-Carotene, ß-Carotene, α-Tocopherol, γ-Tocopherol, and GC risk. CONCLUSION: The pooled analysis demonstrated that high levels of anti-Helicobacter pylORi IgG, PGI<30µg/L and serum PGI/II ratio <3 and low levels of ferritin, iron and transferrin were associated with risk of GC.

Primary splenic diffuse large B-cell lymphoma presenting as a splenic abscess.

Diffuse large B-cell lymphoma (DLBCL) arising in the spleen, also known as primary splenic DLBCL (PS-DLBCL), is a rare form of malignant lymphoma. It is defined as a lymphoma confined to the spleen or involving splenic hilar lymph nodes. Here we report a case of PS-DLBCL with CD30. The patient was a 62-year-old who presented with 2 weeks of left flank pain, chills, and abdominal distension. Computed tomography identified an 8-cm splenic mass with central necrosis interpreted as an abscess. A drain was placed, yielding purulent necrotic material; cytologically, only neutrophils were identified. However, purulent drainage continued for 28 days without resolution, prompting splenectomy. Pathological dissection revealed a multinodular mass with central necrosis. Microscopic examination revealed extensive karyorrhexis, abundant ghosts of large cells, and scattered large cells with pleomorphic, multilobated, and vesicular nuclei with moderately abundant cytoplasm. Immunohistochemical staining revealed large, atypical cells positive for CD20, CD30, CD45, PAX5, MYC (>40%), MUM1 (>30%), and p53 (focally). The large cells were negative for CD3 (polyclonal), CD4, CD5, CD8, CD10, CD15, CD34, BCL2, BCL6, AE1/AE3, S100, HHV8, and ALK. The Ki-67 proliferation rate was approximately 80% in large cells. Notably, this PS-DLBCL was positive for CD30, an unusual finding among non-Hodgkin B-cell lymphomas, which, coupled with the Reed-Sternberg-like morphology, raised the possibility of classic Hodgkin lymphoma. Therefore, we reviewed the literature to confirm the unique features of this large B-cell lymphoma, its abscess-like appearance, and its expression of CD30.

Pediatric combined hepatocellular-cholangiocarcinoma (cHCC-CC) with neuroendocrine features: distinguishing genetic alterations detected by chromosomal microarray.

BACKGROUND: Liver tumors exhibiting hepatocellular, cholangiocarcinoma, and neuroendocrine features are extremely rare, with only five cases reported in the literature. CASE PRESENTATION: We present an unusual case of a combined hepatocellular-cholangiocarcinoma (cHCC-CC) with neuroendocrine features in a pediatric patient. A 16-year-old presented with abdominal pain and a 21.0 cm mass in the right hepatic lobe with extension into the left lobe. Histology showed a poorly differentiated tumor with a solid, tubuloglandular, and microcystic architecture. Immunohistochemistry results were negative for hepatic markers, positive for markers of biliary differentiation, and positive for neuroendocrine differentiation. The neoplasm was reviewed at several institutions with differing diagnoses. Single nucleotide polymorphism (SNP) chromosomal microarray (CMA) showed large deletions within chromosomes 6q and 13q in both the hepatocellular-like areas and the cholangiocarcinoma-like areas, with additional large deletions in the cholangiocarcinoma-like areas, supporting origin from hepatocellular carcinoma. The final diagnosis was a cHCC-CC with neuroendocrine features. CONCLUSIONS: Diagnosis of cHCC-CCs relies predominately on histomorphology, as per the 2018 International Consensus Group on the nomenclature of cHCC-CC. These findings in this case support that the pathological classification of these lesions be based on molecular data, which could better direct treatment. Further classification of cHCC-CCs and determination of their clinicopathological relevance will require more interobserver consistency and continued molecular profiling of these lesions.

Association of sodium intake with adverse left atrial function and left atrioventricular coupling in Chinese.

OBJECTIVES: High sodium intake is strongly associated with hypertension and obesity. This study aims to investigate the relationship between 24-h urinary sodium (a surrogate measure of sodium intake), ambulatory blood pressure parameters, left atrial function, and left atrioventricular coupling. Further, we intend to examine whether blood pressure and BMI might be mediators of the relationship between 24-h urinary sodium and subclinical cardiac function. METHODS: Our study had 398 participants, all of whom were subjected to 24-h urine collection, 24-h ambulatory blood pressure measurement, and cardiac magnetic resonance imaging. RESULTS: The average age of the participants was 55.70 ±â€Š11.30 years old. The mean urinary sodium of the participants was 172.01 ±â€Š80.24 mmol/24 h. After adjusting for age, sex, history of diabetes, smoking status, alcohol consumption, and use of diuretics, 24-h urinary sodium was correlated with multiple ambulatory blood pressure parameters, BMI, left atrial function, and the left atrioventricular coupling index (LACI) (P < 0.05). Mediation analysis showed that BMI explained 16% of the indirect effect of 24-h urinary sodium and left atrial function and 30% of the indirect effect of LACI. Independent of the mediator, 24-h urinary sodium had a significant direct effect on left atrial function and left atrioventricular coupling. CONCLUSIONS: Higher 24-h urinary sodium was associated with a greater BMI as well as poor left atrial function and left atrioventricular coupling, and the BMI mediated the relationship between 24-h urinary sodium and subclinical left cardiac function. Furthermore, and more importantly, 24-h urinary sodium may have directly affected the left atrial function and left atrioventricular coupling independent of intermediary factors.

Risk Factors for Arteriovenous Fistula Thrombus Development: A Systematic Review and Meta-Analysis.

BACKGROUND: Risk factors like female sex, fistula location, hypertension, albumin, diabetes, arteriovenous graft (AVG), age, and other factors are related to arteriovenous fistula thrombus (AVFT), but the consistency and magnitude of their associations have not been confirmed by meta-analysis. OBJECTIVES: The purpose of this study was to provide a comprehensive and up-to-date synthesis of evidence on the association between potential risk factors and AVFT. METHODS: In this systematic review and meta-analysis, PubMed, Embase, Cochrane Library, and Web of Science databases were searched for articles published up to April 20th, 2022, and cohort, cross-sectional, and case-control studies examining the association (odds ratio [OR]) between potential risk factors and AVFT were identified. The other inclusion criteria were sufficient data for analysis and nonoverlapping datasets, excluding reviews, meta-analyses, and articles with overlapping datasets. Extracted variables included first author, publication year, study type, sample size, percentage of women, vascular access type, risk or protective factors, and measure of association (adjusted estimates of effect of all risk factors). The study protocol is registered at PROSPERO (CRD42020201884) and followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Among the 27 identified studies, data from 24 cohort, 2 case-control, and 1 cross-sectional study were included in this review. When compared to non-AVFT, our data showed that the significant risk factors were AVG (pooled OR = 6.28, 95% CI = 1.79-22.02, p = 0.004, I2 = 87%), age (pooled OR = 1.06, 95% CI = 1.00-1.13, p = 0.05, I2 = 98%), female sex (pooled OR = 2.62, 95% CI = 2.56-2.69, p < 0.00001, I2 = 0%), C-reactive protein (pooled OR = 1.18, 95% CI = 1.08-1.30, p = 0.0005, I2 = 90%), fistula site (distal) (pooled OR = 3.64, 95% CI = 1.74-7.62, p = 0.0006, I2 = 47%), hypertension (pooled OR = 1.21, 95% CI = 1.00-1.47, p = 0.05, I2 = 46%), CD34+KDR+ cell (pooled OR = 1.85, 95% CI = 1.33-2.57, p = 0.0002, I2 = 0%), and eprex use (pooled OR = 5.36, 95% CI = 1.82-15.77, p = 0.002, I2 = 0%). CONCLUSIONS: The meta-analysis suggests that AVG, age, female sex, CRP level, fistula site (distal), hypertension, CD34+KDR+ cell, and the use of eprex are independent risk factors for AVFT. Therefore, clinical medical staff should treat these risk factors carefully, identify them early, and prevent them early to reduce the occurrence of AVFT.

A rare case of complex variant translocation of t(9;22;16)(q34;q11.2;q24) in a newly diagnosed patient with chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm associated with the dysregulated production of myeloid cells. The Philadelphia chromosome (Ph), t(9;22)(q34;q11), is a hallmark of the disease and found in 90-95% of diagnosed CML patients. The balanced, reciprocal translocation places the genes BCR and ABL1, next to each other, resulting in an increase of kinase activity. Additional cases involve complex variants, including translocation events involving an additional chromosome with the creation of the Ph chromosome. A rare three-way Ph chromosome complex variant, t(9;22;16)(q34;q11.2;q24), was identified in a 40-year-old female who presented with visual changes and leukocytosis. Cytogenetic analysis by G-banding revealed the presence of a three-way translocation involving the long arms of chromosomes 9, 22, and 16. Fluorescence in situ hybridization with a dual-color fusion probe confirmed the presence of the BCR::ABL1 fusion.

Relationship between Proton Pump Inhibitors and Adverse Effects in Hemodialysis Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Currently, the interaction between proton pump inhibitors (PPIs) and their effects on hemodialysis (HD) patients has not been clarified. OBJECTIVES: Here, we aimed to explore the association between PPIs and adverse outcomes in HD patients. METHODS: A search was performed on the PubMed, Embase, Cochrane Library, and Web of Science databases for relevant articles published up to April 10, 2022. Studies examining the association (odds ratio [OR]) between PPIs and side effects were identified. The study followed guidelines prescribed in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), and was registered with PROSPERO (CRD42021291177). RESULTS: A total of 12 studies comprising 4,227,497 HD patients with PPIs were identified. Results showed that PPI use was associated with an increased risk of bone fracture and hip fracture in the HD patients (pooled OR = 1.29, 95% CI = 1.21-1.37, p < 0.00001, I2 = 0%; pooled OR = 1.37, 95% CI = 1.12-1.67, p = 0.002, I2 = 82%). Besides, HD patients who received PPIs were more likely to develop hypomagnesemia compared with those who did not receive PPIs (pooled OR = 2.79, 95% CI = 1.95-4.00, p < 0.00001, I2 = 0%). In addition, PPIs use was linked to abdominal aortic calcification and all-cause mortality (pooled OR = 2.03, 95% CI = 1.28-3.24, p = 0.003, I2 = 0%) (pooled OR = 1.44, 95% CI = 1.17-1.78, p = 0.0006, I2 = 0%). CONCLUSIONS: Taken together, the present results demonstrate that PPIs use in HD patients is independently associated with adverse reactions such as hip fracture, hypomagnesemia, abdominal aortic calcification, and all-cause mortality. Thus, the use of PPIs in HD patients should be carefully evaluated and optimized.

Proposal of Diagnostic Approach of Periodontal Primary Non Hodgkin Lymphoma of Bone with Flow Cytometry as an Essential Diagnostic Component.

BACKGROUND: Primary bone lymphoma is a rare type of lymphoid neoplasm with favorable prognosis, where Primary Non Hodgkin Lymphoma of bone (PB-NHL) is most common with the subtype. Amongst PB-NHL, diffuse large Bcell lymphoma represents the majority of cases. The mandible is a very uncommon site of involvement, presenting as a painful bone mass with high suspicion of osteomyelitis. METHODS: We report the case of a 45-year-old male with no significant past medical history who was admitted to the hospital with a large right jaw mass and pain after recent tooth removal. The original tissue biopsy was not diagnostic, and cultures were found to be negative for microorganisms. Due to enlargement of the mass, a fine needle aspiration (FNA) was done. At the time of rapid onsite evaluation of the FNA, atypical lymphoid cells were seen, and material was obtained for flow cytometry (FC) evaluation. This revealed an aberrant clonal B-cell population. The consequent immunohistochemical evaluation of original material supported the diagnosis of PB-NHL. After chemotherapy patient improved. RESULTS: After an extensive English language literature review, we identified and summarized the clinical presentations, diagnostic procedures, histopathologic features, treatment methods, and outcomes of forty-two cases of periodontal PB-NHL. Based on our findings, we propose a set of clinical features at initial presentation to increase the clinical suspicion of periodontal PB-NHL for practitioners. CONCLUSION: Based on our institution's experience and the literature review conclusions, we propose the University of Texas Medical Branch diagnostic approach for PB-NHL and suggest that FNA and FC should be utilized as the essential diagnostic component. The fast and efficient diagnosis of PB-NHL can facilitate the correct treatment and sufficiently improve patient care.