Predictive value of inflammatory markers for the spontaneous passage of Ureteral stones: a comprehensive systematic review with meta analysis.

Urolithiasis is a common disease that affects approximately one-fifth of the global population. This systematic review explores the predictive role of inflammatory markers for the spontaneous passage of ureteral stones. The literature was systematically searched via Google Scholar, PubMed/MEDLINE, the Cochrane Library, Science Direct, CINAHL, Web of Science, and EMBASE databases to identify papers published until 2023. Overall, 26 articles were identified, of which 10 were excluded. The remaining 16 papers reported 2,695 patients (1,723 males and 972 females), with 1,654 (61.37%) experiencing spontaneous stone passage (SSP) and 1,041 (38.63%) not experiencing it (non-SSP). Stones located in the upper part of the ureter were less likely to pass spontaneously (152/959, 15.94% in the SSP group vs. 180/546, 32.48% in the non-SSP group; p < 0.001). Mid-ureteral stones were present in 180/959 (18.75%) of the SSP group compared to 84/546 (14.52%) of the non-SSP group (p = 0.0974). Lower ureteral stones were more likely to pass spontaneously, with 627/959 (63.31%) in the SSP group compared to 282/546 (49.36%) in the non-SSP group (p < 0.001). No significant correlation was found between most inflammatory markers and SSP (p > 0.05). However, procalcitonin levels were lower in the SSP group compared to the non-SSP group (132.7 ± 28.1 vs. 207 ± 145.1, respectively) (p < 0.001). This systematic review has revealed that except procalcitonin, most inflammatory markers do not offer significant predictive capability for ureteral SSP.

Cutaneous Crohn disease presenting as "knife-edged" ulcers: a case report.

BACKGROUND: CCD presents as non-caseating granulomas within the skin at a site distant from the GI tract. CCD is a debilitating extraintestinal sequela of CD that can sometimes precede its GI manifestations. In the absence of GI symptoms, the histopathologic and clinical features of CCD can present as a variety of inflammatory skin conditions that can range from ruptured follicle-associated granulomas to cutaneous ulcerations. While a variety of therapeutic options for patients with CCD and concurrent luminal CD have been described in the literature, there is no standard treatment algorithm for the management of refractory CCD with limited or covert GI involvement. CASE REPORT: The authors discuss the case of a 33-year-old female who presented to the wound care clinic with multiple "knife-edged" cutaneous ulcerations involving the intertriginous spaces, found to be consistent with CCD. Her original cutaneous symptoms and diagnosis manifested with minimal GI involvement and responded to IVIG treatment. CONCLUSIONS: This case supports the inclusion of CCD in the differential diagnosis in patients with knife-edged granulomatous skin lesions in intertriginous locations. This clinical condition may present in the setting of no or limited GI symptoms. The management of CCD and a proposed treatment algorithm are also presented.

KRAS and MT-CO1 genes in colorectal cancer: a molecular investigation.

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide. The tumor suppressor gene MT-CO1, and Kristen Rat Sarcoma Virus (KRAS), an oncogene are primarily responsible for controlling cell apoptosis, cell cycle arrest, and cell proliferation, and any irregularities in these genes could lead to cancer. This study aims to examine the expression of KRAS and MT-CO1 in CRC biopsy specimens and investigate their relationship with one another in CRC patients residing in the Erbil city of Kurdistan Region, Iraq. The study involved categorizing 42 sets of colorectal cancer tissues and their corresponding controls based on their types and patients' clinical characteristics. The expression of KRAS and MT-CO1 in the samples was assessed using Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR), with statistical significance set at p<0.05. The expression of KRAS was found to be significantly higher in CRC compared to the control (n=42, p=0.0001). On the other hand, the expression of MT-CO1 did not exhibit significant differences compared to the control group with a p-value of 0.12. Furthermore, the Chi-square and correlation analysis results depicted that MT-CO1 expression negatively correlates with KRAS expression (p= 0.0001, r= -0.047) in CRC tissues. In conclusion, the variation in the expression of KRAS and MT-CO1, and their correlations could potentially serve as a good indicator in the detection and prognosis of CRC, which might lead to better translational research on the same. However, for a better understanding of the underlying mechanisms, further analysis is required.

Spermatocytic tumor of the testis: A case report and mini­review of the literature.

Spermatocytic tumors are a rare type of testicular cancer, comprising <1% of all testicular malignancies. This type of cancer typically affects males in their 60s and 70s and rarely metastasizes; however, it poses a threat to the health of affected individuals if left untreated. The present study describes the case of a 68-year-old male patient with this type of tumor, including a presentation of his initial symptoms, treatment and subsequent monitoring. A male patient, aged 68 years, visited the authors' clinic with an asymptomatic mass in the right testicle. The mass had been progressively increasing in size for a duration of 5 years following a history of blunt injury. During the examination, a noticeable, painless enlargement was detected in the right testis, whereas the left testis appeared to be in a normal state. Tumor markers were within normal limits. Imaging revealed a complex mass (11x8x7 cm) almost replacing the right testis, with no detectable lymph nodes. A right radical orchidectomy was performed under spinal anesthesia. A histopathological examination revealed a spermatocytic tumor. The post-operative period was uneventful, with no metastasis detected in the CT scans. The patient was discharged with instructions for regular follow-up appointments. The case presented herein highlights a rare spermatocytic tumor in a 68-year-old male. The early detection and treatment of testicular tumors, regardless of age, are crucial for a good prognosis.

Prognostic factors in renal cell carcinoma: A single­center study.

Renal cell carcinoma (RCC) is a heterogeneous and complex disease with numerous pathophysiologic variants. ~40% of patients succumb due to the progression of the disease, making RCC the most fatal of the common urologic malignancies. Prognostic factors are indicators of the progression of the disease, and the precise determination of these factors is important for evaluating and managing RCC. In the present study, it was aimed to determine and find associations among the histopathological features of RCCs and their impact on survival and metastasis. This is a cross-sectional study of RCC cases who have undergone partial or radical nephrectomy from March 2008 to October 2021 and have been pathologically reviewed at Shorsh General Teaching Hospital in Sulaimani, Iraq. The data in the pathology studies were supplemented by follow-up of the patients to obtain information about survival, recurrence and metastasis. In total, 228 cases of RCC were identified, among whom 60.5% were men and 39.5% were women, with a median age of 51 years. The main tumor types were clear cell RCC (71.1%), papillary RCC (13.6%), and chromophobe RCC (11%). Various measures of aggressiveness, including tumor necrosis, sarcomatoid change, microvascular invasion, and parameters of invasiveness (invasion of the renal sinus and other structures), were significantly correlated with each other, and they were also associated with reduced overall survival and an increased risk of metastasis on univariate analysis. However, on multivariate analysis, only tumor size and grade, and microvascular invasion retained statistical significance and were associated with a lower survival rate. In conclusion, pathological parameters have an impact on prognosis in RCC. The most consistent prognostic factors can be tumor size and grade, and microvascular invasion.

Non-operative management of pilonidal sinus disease; classification and outcome.

The characteristics of the pilonidal sinus that are associated with recurrence have scarcely been investigated in the literature. This study aims to evaluate the outcomes of patients with sacrococcygeal pilonidal sinus disease who were managed by a non-operative technique using Salih's preparation. This study also tries to classify the patients according to the features that determine the outcome of the intervention. This is a single-group cohort study that enrolled consecutive patients that had pilonidal sinus. All the patients were managed using Salih's preparation. The patients were seen at the clinic 6 weeks after the intervention to record data of recurrence. The Statistical Package for the Social Sciences (SPSS) Version 25 was used for coding and analysing the data. Test of significance and odds ratio were calculated for all of the features. The total number of patients receiving Salih's preparation was 12 123 cases, of which only 3529 patients were included in this study. The mean age of the participants was 26.95 years, ranging from 14 to 55 years. The most significant factor related to the recurrence was the presence of an abscess. After summation of all odd ratios, the percentage of each one from the total was calculated, and accordingly, the patients were divided into three classes. Non-operative methods using a preparation with antimicrobial and sclerosing properties can be an alternative for surgical intervention with a lower risk of recurrence. Classification of patients based on specific criteria can give clinicians and even patients themselves a vision of the chance of recurrence and treatment success.

Secondary renal amyloidosis due to primary Sjogren's syndrome: a case report.

Amyloidosis is a rare disorder characterized by the deposition of abnormal proteins in extracellular tissues, resulting in the dysfunction of vital organs and, eventually, death. The occurrence of amyloidosis due to primary Sjogren's syndrome (pSS) is a rare finding. This study describes a rare case of pSS complicated by amyloid-associated amyloidosis. Case presentation: A 35-year-old male was diagnosed with nephrotic syndrome and secondary amyloidosis caused by pSS. He had microscopic hematuria, a creatinine level of 6.59 mg/dl, and an elevated erythrocyte sedimentation rate of 107 mm/hrs. Furthermore, investigations of antinuclear antibodies, antimitochondrial antibodies, SSA, SSA native, and Ro-52 recombinant as well as rheumatoid factor showed positive results. After establishing the diagnosis of pSS through clinical, physical, and laboratory assessments, a renal biopsy was performed, which revealed the occurrence of secondary amyloidosis. Clinical discussion: The risk of developing secondary amyloidosis depends on the extent of elevated serum amyloid levels as well as persistent subclinical inflammation. The definitive diagnosis of amyloidosis requires histological confirmation of amyloid fibril deposition in tissue. Conclusion: Secondary renal amyloidosis is an unusual condition in patients with pSS. Still, it should be regarded in the differential diagnosis of patients with proteinuria and/or renal failure, and a renal biopsy should be performed.

Renal cell carcinoma T staging: Diagnostic accuracy of preoperative contrast-enhanced computed tomography.

Renal cell carcinoma (RCC) accounts for 1-2% of all malignancies and is the most common renal tumor in adults. Imaging studies are used for diagnosis and staging. Tumor-Node-Metastasis staging strongly affects prognosis and management, while contrast-enhanced computed tomography (CECT) is regarded as a standard imaging technique for local and distant staging. The present study aimed to evaluate the accuracy of CECT for the preoperative staging of RCC by using surgical and pathological staging as the reference methods. This single-center prospective study was conducted between October 2019 and November 2021. The preoperative abdominal CT scans of patients suspected of having RCC were reviewed. Imaging data were collected, including tumor side and size, and perinephric fat invasion. Intraoperative notes were recorded, including the operation type, perinephric fat invasion, renal vein (RV) or inferior vena cava (IVC) tumor extension, and surrounding organ invasion. pathological data were collected on tumor size, RCC type, presence of clear margins, presence of renal capsule or perinephric fat invasion, renal sinus or pelvicalyceal system (PCS) invasion, segmental or main RV extension, and the involvement of Gerota's fascia and nearby organs. Preoperative CECT revealed that 42 out of 59 tumors had a greater maximum diameter than the pathological specimen, with an overall disparity of 0.25 cm. The specificity of CT for the detection of tumor invasion of the perinephric and renal sinus fat and PCS was 95%, and the sensitivity ranged from 80 to 88%. CT had an 83% sensitivity and a 95 specificity in detecting T4 stage cancer, with a 100% specificity for adrenal invasion. The concordance between radiographic and histological results for RV and IVC involvement was high, with specificities of 94 and 98%, and sensitivities of 80 and 100%, respectively. Overall accuracy for correct T staging was 80%. In conclusion, CECT is accurate in the local T staging of RCC, with high sensitivity and specificity for estimating tumor size and detecting extension to nearby structures and venous invasion.

Multifocal demyelinating leukoencephalopathy and oligodendroglial lineage cell loss with immune effector cell-associated neurotoxicity syndrome (ICANS) following CD19 CAR T-cell therapy for mantle cell lymphoma.

Immune effector cell-associated neurotoxicity syndrome (ICANS) is a prevalent condition seen after treatment with chimeric antigen receptor T-cell (CAR T) therapy and other cancer cell therapies. The underlying pathophysiology and neuropathology of the clinical syndrome are incompletely understood due to the limited availability of brain tissue evaluation from patient cases, and a lack of high-fidelity preclinical animal models for translational research. Here, we present the cellular and tissue neuropathologic analysis of a patient who experienced grade 4 ICANS after treatment with anti-CD19 CAR T therapy for mantle cell lymphoma. Our pathologic evaluation reveals a pattern of multifocal demyelinating leukoencephalopathy associated with a clinical course of severe ICANS. A focused analysis of glial subtypes further suggests region-specific oligodendrocyte lineage cell loss as a potential cellular and pathophysiologic correlate in severe ICANS. We propose a framework for the continuum of neuropathologic changes thus far reported across ICANS cases. Future elucidation of the mechanistic processes underlying ICANS will be critical in minimizing neurotoxicity following CAR T-cell and related immunotherapy treatments across oncologic and autoimmune diseases.

Dynamin-2 deficiency causes age- and sex-dependent neutropenia and myelodysplasia in mice.

The dynamins are a family of ubiquitously expressed GTPase proteins, best known for their role in membrane remodeling. Their contribution to hematopoiesis is incompletely recognized. Individuals with Charcot-Marie-Tooth disease with dynamin-2 (DNM2) mutations often develop neutropenia. We previously reported that dynamin (DNM) inhibition impairs SDF1a-mediated migration in megakaryocytes. Here, we report on conditionally Dnm2 deleted mice in hematopoietic tissues using the Vav-Cre murine strain. Homozygous Dnm2 deletion in blood tissues is embryonic lethal. Dnm2het male mice only developed a slightly decreased hemoglobin level. Dnm2het female mice developed leukopenia by 40 weeks of age and neutropenia by 65 weeks of age. Flow cytometry revealed decreased lineage-negative cells and granulocyte-monocyte progenitors in Dnm2het female mice. Immunohistochemical staining of bone marrow (BM) for mature neutrophils with Ly6G was decreased and myelodysplastic features were present in the BM of Dnm2het female mice. A linear distribution of Ly6G+ BM cells along blood vessels was observed in fewer Dnm2het mice than in controls, suggesting that the migration pattern in the marrow is altered. Marrow neutrophils treated with dynamin inhibitor, dynasore, showed increased cell surface CXCR4, suggesting that abnormal migration results in marrow neutrophil retention. Dnm2het female mice also developed splenomegaly secondary to germinal center hyperplasia at younger ages, suggesting perturbed immunity. In summary, female mice with BM Dnm2 haploinsufficiency developed neutropenia as they aged with decreased granulocyte progenitor production and migration defects. Our studies indicate a potential mechanism for the development of chronic idiopathic neutropenia, a disease that predominantly presents in middle-aged women.

Preferentially Expressed Antigen in Melanoma Immunohistochemistry Labeling in Uveal Melanomas.

Introduction: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, and despite treatment of the primary tumor, approximately 15%-50% of patients will develop metastatic disease. Based on gene expression profiling (GEPs), UM can be categorized as Class 1A (low metastatic risk), Class 1B (intermediate metastatic risk), or Class 2 (high metastatic risk). PReferentially expressed Antigen in MElanoma (PRAME) status is an independent prognostic UM biomarker and a potential target for immunotherapy in metastatic UM. PRAME expression status can be detected in tumors using reverse-transcription polymerase chain reaction (RT-PCR). More recently, immunohistochemistry (IHC) has been developed to detect PRAME protein expression. Here, we employed both techniques to evaluate PRAME expression in 18 UM enucleations. Methods: Tumor material from the 18 UM patients who underwent enucleation was collected by fine-needle aspiration before or during enucleation and sent for GEP and PRAME analysis by RT-PCR. Histologic sections from these patients were stained with an anti-PRAME monoclonal antibody. We collected patient demographics and tumor characteristics and included this with our analysis of GEP class, PRAME status by RT-PCR, and PRAME status by IHC. PRAME IHC and RT-PCR results were compared. Results: Twelve males (12/18) and 6 females (6/18) with an average age of 60.6 years underwent enucleation for UM. TNM staging of the UM diagnosed Stage I in 2 patients (2/18), Stage II in 7 patients (7/18), Stage III in 8 patients (8/18), and Stage IV in 1 (1/18). GEP was Class 1A in 6 tumors (6/18), Class 1B in 6 tumors (6/18), and Class 2 in 6 tumors (6/18). PRAME IHC showed diffusely positive labeling of all UM cells in 2/18 enucleations; negative IHC labeling of UM cells in 9/18 enucleations; and IHC labeling of subsets of UM cells in 7/18 enucleations. Eleven of the 17 UMs tested for PRAME by both RT-PCR and IHC had consistent PRAME results. In the remaining 6/17 cases tested by both modalities, PRAME results were discordant between RT-PCR and IHC. Conclusions: We find that PRAME IHC distinguishes PRAME-positive and PRAME-negative UM tumor cells. Interestingly, IHC reveals focal PRAME expression in subsets of tumor cells consistent with tumor heterogeneity. PRAME RT-PCR and IHC provide concordant results in most of our cases. We suggest that discordance in PRAME results could arise from spatial or temporal variation in PRAME expression between tumor cells. Further studies are required to determine the prognostic implications of PRAME IHC in UM.

Prospective intraoperative and histologic evaluation of cavernous sinus medial wall invasion by pituitary adenomas and its implications for acromegaly remission outcomes.

Recurrence and biochemical remission rates vary widely among different histological subtypes of pituitary adenoma. In this prospective study, we evaluated 107 consecutive primary pituitary adenomas operated on by a single neurosurgeon including 28 corticotroph, 27 gonadotroph, 24 somatotroph, 17 lactotroph, 5 null-cell and 6 plurihormonal. In each case, we performed direct endoscopic intraoperative inspection of the medial wall of the cavernous sinus, which was surgically removed when invasion was visualized. This was performed irrespective of tumor functional status. Medial wall resection was performed in 47% of pituitary adenomas, and 39/50 walls confirmed pathologic evidence of invasion, rendering a positive predictive value of intraoperative evaluation of medial wall invasion of 78%. We show for the first-time dramatic disparities in the frequency of medial wall invasion among pathological subtypes. Somatotroph tumors invaded the medial wall much more often than other adenoma subtypes, 81% intraoperatively and 69% histologically, followed by plurihormonal tumors (40%) and gonadotroph cell tumors (33%), both with intraoperative positive predictive value of 100%. The least likely to invade were corticotroph adenomas, at a rate of 32% intraoperatively and 21% histologically, and null-cell adenomas at 0%. Removal of the cavernous sinus medial wall was not associated with permanent cranial nerve morbidity nor carotid artery injury, although 4 patients (all Knosp 3-4) experienced transient diplopia. Medial wall resection in acromegaly resulted in the highest potential for biochemical remission ever reported, with an average postoperative day 1 GH levels of 0.96 ug/L and surgical remission rates of 92% based on normalization of IGF-1 levels after surgery (mean = 15.56 months; range 3-30 months). Our findings suggest that tumor invasion of the medial wall of the cavernous sinus may explain the relatively low biochemical remission rates currently seen for acromegaly and illustrate the relevance of advanced intradural surgical approaches for successful and durable outcomes in endonasal pituitary surgery for functional adenomas.

HectoSTAR µLED Optoelectrodes for Large-Scale, High-Precision In Vivo Opto-Electrophysiology.

Dynamic interactions within and across brain areas underlie behavioral and cognitive functions. To understand the basis of these processes, the activities of distributed local circuits inside the brain of a behaving animal must be synchronously recorded while the inputs to these circuits are precisely manipulated. Even though recent technological advances have enabled such large-scale recording capabilities, the development of the high-spatiotemporal-resolution and large-scale modulation techniques to accompany those recordings has lagged. A novel neural probe is presented in this work that enables simultaneous electrical monitoring and optogenetic manipulation of deep neuronal circuits at large scales with a high spatiotemporal resolution. The "hectoSTAR" micro-light-emitting-diode (µLED) optoelectrode features 256 recording electrodes and 128 stimulation µLEDs monolithically integrated on the surface of its four 30-µm thick silicon micro-needle shanks, covering a large volume with 1.3-mm × 0.9-mm cross-sectional area located as deep as 6 mm inside the brain. The use of this device in behaving mice for dissecting long-distance network interactions across cortical layers and hippocampal regions is demonstrated. The recording-and-stimulation capabilities hectoSTAR µLED optoelectrodes enables will open up new possibilities for the cellular and circuit-based investigation of brain functions in behaving animals.

MRI Radiogenomics of Pediatric Medulloblastoma: A Multicenter Study.

Background Radiogenomics of pediatric medulloblastoma (MB) offers an opportunity for MB risk stratification, which may aid therapeutic decision making, family counseling, and selection of patient groups suitable for targeted genetic analysis. Purpose To develop machine learning strategies that identify the four clinically significant MB molecular subgroups. Materials and Methods In this retrospective study, consecutive pediatric patients with newly diagnosed MB at MRI at 12 international pediatric sites between July 1997 and May 2020 were identified. There were 1800 features extracted from T2- and contrast-enhanced T1-weighted preoperative MRI scans. A two-stage sequential classifier was designed-one that first identifies non-wingless (WNT) and non-sonic hedgehog (SHH) MB and then differentiates therapeutically relevant WNT from SHH. Further, a classifier that distinguishes high-risk group 3 from group 4 MB was developed. An independent, binary subgroup analysis was conducted to uncover radiomics features unique to infantile versus childhood SHH subgroups. The best-performing models from six candidate classifiers were selected, and performance was measured on holdout test sets. CIs were obtained by bootstrapping the test sets for 2000 random samples. Model accuracy score was compared with the no-information rate using the Wald test. Results The study cohort comprised 263 patients (mean age ± SD at diagnosis, 87 months ± 60; 166 boys). A two-stage classifier outperformed a single-stage multiclass classifier. The combined, sequential classifier achieved a microaveraged F1 score of 88% and a binary F1 score of 95% specifically for WNT. A group 3 versus group 4 classifier achieved an area under the receiver operating characteristic curve of 98%. Of the Image Biomarker Standardization Initiative features, texture and first-order intensity features were most contributory across the molecular subgroups. Conclusion An MRI-based machine learning decision path allowed identification of the four clinically relevant molecular pediatric medulloblastoma subgroups. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Chaudhary and Bapuraj in this issue.

Risk of malignancy associated with the diagnostic categories proposed by the Papanicolaou Society of Cytopathology for pancreaticobiliary specimens: An institutional experience.

BACKGROUND: The guidelines published by the Papanicolaou Society of Cytopathology (PSC) intend to unify the reporting language in pancreaticobiliary specimens and improve communication between cytopathologists and clinicians. The six categories in the system will determine the best management for patients. However, there is limited evidence regarding the risk of malignancy (ROM) associated with each category. METHODS: A retrospective search was performed for pancreaticobiliary fine-needle aspiration (FNA) reports with corresponding surgical follow-up. Cases were reclassified according to the PSC. The ROM, sensitivity, specificity, positive predictive value, and negative predictive value were calculated for each category. RESULTS: A total of 297 cases were identified and reclassified as: 30 nondiagnostic (category I), 45 negative for malignancy (II), 20 atypical (III), 42 neoplastic: other (IVB), 19 suspicious for malignancy (V), and 141 malignant (VI). The absolute ROM was 10% for category I, 8.9% for category II, 60% for category III, 4.8% for category IV when the neoplasms were not characterized as malignant, and 100% when categorized as malignant; 100% for category V, and 95.7% for category VI. Sensitivity, specificity, positive predictive value, and negative predictive value for neoplasia and malignancy, including categories IV to VI, were 96.6%, 88.4%, 97.5%, and 84.4%, respectively. CONCLUSIONS: The categories developed by the PSC stratify the ROM. Aspirates designated as categories V and VI had the highest ROM. Our rate of atypical category complies with the recommended rate of <10%. This scheme provides valuable information to clinicians treating patients with pancreatic lesions.

Intraplacental Hepatic Heterotopia.

Background: Placental hepatic heterotopia is a benign lesion with unclear histogenesis hypothesized to be of hepatocytic differentiation of yolk sac elements. Of the 14 hepatic heterotopia cases previously reported, 12 cases occurred in preterm labor.Case report: A case of intraplacental hepatic heterotopia in a 27-year-old female with pre-term delivery at 31 + 5 weeks gestational age is described. Histopathological examination revealed a well-demarcated lesion with cohesive, monotonous cells and pale to clear cytoplasm. The differential diagnoses of this lesion included benign, primary and metastatic malignant entities. The lesional cells expressed HepPar-1, CAM 5.2, Glypican-3, and AFP, consistent with cells of hepatic origin.Conclusion: Intraplacental hepatic heterotopia is associated with premature labor. Distinguishing this lesion from maternal and fetal malignancies with similar histopathological presentation has important clinical implications in patient care.

Knowledge and Attitude of People With or Without a Medical Education Regarding Organ Donation and Transplant: A Sample From the City of Baghdad.

OBJECTIVES: Organ donation is the driving force for transplant. Awareness about donation and transplant is invaluable for improved transplant services in any country. Our objective was to assess the knowledge and attitude toward organ donation and transplant among medically educated adult Iraqis versus adult Iraqis who were not medically educated, in Baghdad, Iraq. MATERIALS AND METHODS: For this study, we recruited 400 Iraqi residents of Baghdad city from December 1, 2018, to March 1, 2019. We used an interviewer-adm-inistered questionnaire to survey 200 health care professionals and 200 adults who lacked medical education, and then we analyzed the responses from the 2 groups. RESULTS: The study included 165 males and 235 females (mean age 33.73 ± 10.38 years). Most participants (60%) were aware of organ donation, and a health care provider was the main source of their knowledge. Only 11.25% were aware of Iraqi legislation that permits donation after brain death. Nearly 50% of the participants volunteered to be living donors, and 229/400 (57.25%%) volunteered to donate after death. About 50% accepted the idea of organ donation as an act to save life, whomever the donor. The most important barrier was the fear of future risks to health after living donation and body disfigurement after death. There was a statistically significant difference in the knowledge and attitude scores between the 2 groups. From the study sample, 46.5% accepted the concept of incenting living donors or families of deceased donors. CONCLUSIONS: Iraqi people are moderately informed about organ donation and transplant. Medically educated people demonstrated an attitude of greater acceptance. Religion and social beliefs were not barriers to organ donation in the study sample. Regulated governmental application of incentive programs may be a useful strategy at present.

A Novel Brain-Permeant Chemotherapeutic Agent for the Treatment of Brain Metastasis in Triple-Negative Breast Cancer.

Development of metastases to central nervous system (CNS) is an increasing clinical issue following the diagnosis of advanced breast cancer. The propensity to metastasize to CNS varies by breast cancer subtype. Of the four breast cancer subtypes, triple-negative breast cancers (TNBC) have the highest rates of both parenchymal brain metastasis and leptomeningeal metastasis (LM). LM is rapidly fatal due to poor detection and limited therapeutic options. Therapy of TNBC brain metastasis and LM is challenged by multifocal brain metastasis and diffuse spread of LM, and must balance brain penetration, tumor cytotoxicity, and the avoidance of neurotoxicity. Thus, there is an urgent need for novel therapeutic options in TNBCs CNS metastasis. QBS10072S is a novel chemotherapeutic that leverages TNBC-specific defects in DNA repair and LAT1 (L-amino acid transporter type 1)-dependent transport into the brain. In our study, activity of QBS10072S was investigated in vitro with various cell lines including the human TNBC cell line MDA-MB-231 and its brain-tropic derivative MDA-MB-231-BR3. QBS10072S was preferentially toxic to TNBC cells. The efficacy of QBS10072S against brain metastasis and LM was tested using a model of brain metastasis based on the internal carotid injection of luciferase-expressing tumor cells into NuNu mice. The compound was well tolerated, delayed tumor growth and reduced leptomeningeal dissemination, resulting in significant extension of survival. Given that current treatments for LM are palliative with only few studies reporting a survival benefit, QBS10072S is planned to be investigated in clinical trials as a therapeutic for TNBC LM. SIGNIFICANCE: TNBC brain metastasis often involves dissemination into leptomeninges. Treatment options for TNBC leptomeningeal metastasis are limited and are mostly palliative. Our study demonstrates significant efficacy of the brain-penetrating agent QBS10072S against TNBC brain metastasis and leptomeningeal spread.

Comparing Survival of Israeli Acute Paralysis Virus Infection among Stocks of U.S. Honey Bees.

Among numerous viruses that infect honey bees (Apis mellifera), Israeli acute paralysis virus (IAPV) can be linked to severe honey bee health problems. Breeding for virus resistance may improve honey bee health. To evaluate the potential for this approach, we compared the survival of IAPV infection among stocks from the U.S. We complemented the survival analysis with a survey of existing viruses in these stocks and assessing constitutive and induced expression of immune genes. Worker offspring from selected queens in a common apiary were inoculated with IAPV by topical applications after emergence to assess subsequent survival. Differences among stocks were small compared to variation within stocks, indicating the potential for improving honey bee survival of virus infections in all stocks. A positive relation between worker survival and virus load among stocks further suggested that honey bees may be able to adapt to better cope with viruses, while our molecular studies indicate that toll-6 may be related to survival differences among virus-infected worker bees. Together, these findings highlight the importance of viruses in queen breeding operations and provide a promising starting point for the quest to improve honey bee health by selectively breeding stock to be better able to survive virus infections.