Glomerular Elasticity and Gene Expression Patterns Define Two Phases of Alport Nephropathy.

Rationale: We take a unique approach to understanding the causes of podocyte injury in collagen IV nephropathies, a crucial step in developing targeted therapies for conditions like Alport Syndrome. Objectives: We characterize the structural, functional, and biophysical properties of glomerular capillaries and podocytes in Col4α3 -/- mice and analyze kidney cortex transcriptional profiles at various disease stages. We investigate the effects of the ER stress mitigator TUDCA on these parameters. Furthermore, we used human FSGS associated podocyte enriched genes to identify molecular pathways rescued by TUDCA thereby offering potential therapeutic targets for Alport Syndrome. Findings: We find a clear disease progression timeline in Col4α3 -/- mice. Podocyte injury develops by 3 months, with glomeruli reaching maximum deformability at 4 months, associated with a 40% loss of podocytes. This is followed by progressive stiffening of glomerular capillaries, increasing proteinuria, reduced renal function, inflammatory infiltrates, and fibrosis from months 4 to 8. Bulk RNA sequencing at 2, 4, and 7 months reveals a progressive increase in expression of genes related to cytokine and chemokine signaling, matrix and cell injury, and activation of the TNF pathway, similar to observations in a NEPTUNE FSGS cohort. Podocyte-enriched genes from FSGS patients mapped to mice found that TUDCA, which mitigated glomerular and renal injury suppressed molecular pathways associated with extracellular matrix and basement membrane synthesis, podocyte stress and hypertrophy. Conclusions: We uncover two distinct phases of Col4α3 -/- nephropathy progression. The first is characterized by podocytopathy, increased glomerular capillary deformability and accelerated podocyte loss, and the second by increased capillary wall stiffening and renal inflammatory and profibrotic pathway activation. The response of podocytes to TUDCA treatment provides novel insights into downstream signaling pathways, offering potential therapeutic targets for treating Alport and related nephropathies.

Synergizing structure and function: Cinnamoyl hydroxamic acids as potent urease inhibitors.

The current investigation encompasses the structural planning, synthesis, and evaluation of the urease inhibitory activity of a series of molecular hybrids of hydroxamic acids and Michael acceptors, delineated from the structure of cinnamic acids. The synthesized compounds exhibited potent urease inhibitory effects, with IC50 values ranging from 3.8 to 12.8 µM. Kinetic experiments unveiled that the majority of the synthesized hybrids display characteristics of mixed inhibitors. Generally, derivatives containing electron-withdrawing groups on the aromatic ring demonstrate heightened activity, indicating that the increased electrophilicity of the beta carbon in the Michael Acceptor moiety positively influences the antiureolytic properties of this compounds class. Biophysical and theoretical investigations further corroborated the findings obtained from kinetic assays. These studies suggest that the hydroxamic acid core interacts with the urease active site, while the Michael acceptor moiety binds to one or more allosteric sites adjacent to the active site.

Demystifying Breast Disease Markers.

Breast imaging radiologists regularly perform image-guided biopsies of suspicious breast lesions based on features that are associated with a likelihood of malignancy ranging from 2% to greater than 95% (Breast Imaging Reporting and Data System categories 4 and 5). As diagnostic partners, pathologists perform histopathologic assessment of these tissue samples to confirm a diagnosis. Correlating the imaging findings with the histopathologic results is an integral aspect of multidisciplinary breast care. Assessment of radiologic-pathologic concordance is vital in guiding appropriate management, as it enables identification of discordant results, minimizing the chance of misdiagnosis. Undersampling can lead to false-negative results, with the frequencies of false-negative diagnoses varying on the basis of multiple factors, including biopsy type (eg, core needle, vacuum-assisted needle), needle gauge, and type of lesion sampled at biopsy (ie, mass, calcifications, asymmetry, architectural distortion). Improving a radiologist's knowledge of macroscopic and microscopic breast anatomy and more common breast diseases and their expected imaging findings ensures more accurate radiologic-pathologic correlation and management recommendations. The histopathologic and molecular characteristics of biopsy-sampled breast lesions aid in making an accurate diagnosis. Hematoxylin-eosin staining provides critical morphologic details, whereas immunohistochemical staining enables molecular characterization of many benign and malignant lesions, which is critical for tailored treatment. The authors review commonly encountered benign and malignant breast diseases, their corresponding histopathologic phenotypes, and the histopathologic markers that are essential to clinching the diagnosis of these entities. As part of a multidisciplinary team that provides optimal patient care, radiologists should be knowledgeable of the foundations of histopathologic diagnosis and the implications for patient management to ensure appropriate radiologic-pathologic concordance. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Implementation of an HIV RNA Qualitative PCR Assay in an HIV Diagnostic Algorithm: A Single-Institution Experience.

OBJECTIVES: Boston Medical Center (BMC) is a private, not-for-profit 514-bed academic medical center and legacy safety net hospital serving a diverse global patient population. BMC recently implemented a new HIV-1/HIV-2 Qualitative RNA PCR (HIV RNA QUAL) cleared by the US Food and Drug Administration to (1) replace antibody discrimination follow-up testing after a reactive fourth-generation (4G) serology screen and (2) use as a stand-alone diagnostic for suspected seronegative acute HIV infection. METHODS: This report summarizes the results of a production monitor for the first 3 months postimplementation. RESULTS: The monitor characterized test utilization, diagnostic turnaround time, impact on send-out testing, results reflexed to HIV RNA discrimination follow-up, and discrepancies between screening and HIV RNA results that necessitated additional investigation. Another element was the novelty of using HIV RNA QUAL while awaiting the existing Centers for Disease Control and Prevention HIV testing algorithm update. The 4G screening components and the HIV RNA QUAL were also used to create an algorithm specific to and compliant with current guidelines for screening patients on HIV preexposure prophylaxis. CONCLUSIONS: Based on our findings, this new test algorithm may be reproducible and instructive at other institutions.

Combined Heart and Kidney Transplantation: Initial Clinical Experience.

INTRODUCTION: Combined solid organ transplantation is infrequently performed in Brazil. The objective of this article is to present our initial experience with combined heart and kidney transplantation. METHODS: From January 2007 to December 2019, four patients were submitted to combined heart and kidney transplantation. Their mean age was 55.7±4.4 years, and three (75%) patients were males. All patients had Chagas cardiomyopathy, two were hospitalized and inotrope dependent, and all patients were on preoperative dialysis (median of 12 months prior to transplant). RESULTS: All patients survived and were in New York Heart Association functional class I at the latest follow-up (mean 34.7±17.5 months). Mean retarded kidney graft function was 22.9±9.7 days. One patient lost the kidney graft two years after the transplant due to Polyomavirus infection. CONCLUSION: Our initial experience of combined heart and kidney transplantation was favorable in selected patients with advanced heart failure and end-stage kidney disease. It requires involvement of a dedicated multispecialty team throughout all the diagnostics and treatment steps.

Combined Heart and Kidney Transplantation: Initial Clinical Experience

ABSTRACT Introduction: Combined solid organ transplantation is infrequently performed in Brazil. The objective of this article is to present our initial experience with combined heart and kidney transplantation. Methods: From January 2007 to December 2019, four patients were submitted to combined heart and kidney transplantation. Their mean age was 55.7±4.4 years, and three (75%) patients were males. All patients had Chagas cardiomyopathy, two were hospitalized and inotrope dependent, and all patients were on preoperative dialysis (median of 12 months prior to transplant). Results: All patients survived and were in New York Heart Association functional class I at the latest follow-up (mean 34.7±17.5 months). Mean retarded kidney graft function was 22.9±9.7 days. One patient lost the kidney graft two years after the transplant due to Polyomavirus infection. Conclusion: Our initial experience of combined heart and kidney transplantation was favorable in selected patients with advanced heart failure and end-stage kidney disease. It requires involvement of a dedicated multispecialty team throughout all the diagnostics and treatment steps.

Donor-derived TB after kidney transplantation: a case report / TB derivada do doador após transplante renal: um relato de caso

Abstract Introduction: Tuberculosis (TB) is a possible serious complication of solid organ transplantation, associated with high mortality and morbidity. Post-transplant TB has varied pathogenesis with many approaches to its prevention, which is the most important way to reduce its incidence. Treatment of TB in organ recipients is challenging because of drug toxicity and interaction with immunosuppressants. Case report: an 18-year-old woman that underwent kidney transplantation from a deceased donor and was discharged with fair renal function was readmitted at 37th postoperative day with fever. CT showed signs of miliary TB and fluid collection besides graft fistulization through the skin. The patient presented positive BAAR in the drained fluid and Koch's bacillus in the urine. She was treated with a four-drug regimen (rifampicin, isoniazid, pyrazinamide, and etambutol), with great response and preserved graft function. We were informed that the recipient of the contralateral kidney also presented post-transplant TB, implying in a donor-derived origin. Conclusion: TB is an important differential diagnosis for infectious complications in patients after solid-organ transplantation, especially in endemic regions. Its initial clinical presentation can be unspecific and it should be suspected in the presence of fever or formation of fluid collections. The suspicion of TB is the key to early diagnosis and satisfactory outcomes in post-transplant TB.

Resumo Introdução: A tuberculose (TB) é uma possível complicação grave do transplante de órgãos sólidos, associada à alta mortalidade e morbidade. A TB pós-transplante tem patogênese variada com muitas abordagens para sua prevenção, que é a forma mais importante de reduzir sua incidência. O tratamento da TB em receptores de órgãos é um desafio devido à toxicidade dos medicamentos e à interação com imunossupressores. Relato de caso: uma mulher de 18 anos que foi submetida a transplante renal de um doador falecido e recebeu alta com função renal adequada foi readmitida no 37º dia de pós-operatório com febre. A TC mostrou sinais de TB miliar e coleção de fluidos além de fistulização do enxerto através da pele. A paciente apresentou BAAR positivo no fluido drenado e bacilo de Koch na urina. Ela foi tratada com um esquema de quatro medicamentos (rifampicina, isoniazida, pirazinamida e etambutol), com ótima resposta e função de enxerto preservada. Fomos informados de que o receptor do rim contralateral também apresentou TB pós-transplante, implicando em uma origem derivada do doador. Conclusão: A TB é um importante diagnóstico diferencial para complicações infecciosas em pacientes após transplante de órgãos sólidos, especialmente em regiões endêmicas. Sua apresentação clínica inicial pode não ser específica e deve ser suspeitada na presença de febre ou formação de coleções de fluidos. A suspeita de TB é a chave para o diagnóstico precoce e desfechos satisfatórios na TB pós-transplante.

Donor-derived TB after kidney transplantation: a case report.

INTRODUCTION: Tuberculosis (TB) is a possible serious complication of solid organ transplantation, associated with high mortality and morbidity. Post-transplant TB has varied pathogenesis with many approaches to its prevention, which is the most important way to reduce its incidence. Treatment of TB in organ recipients is challenging because of drug toxicity and interaction with immunosuppressants. CASE REPORT: an 18-year-old woman that underwent kidney transplantation from a deceased donor and was discharged with fair renal function was readmitted at 37th postoperative day with fever. CT showed signs of miliary TB and fluid collection besides graft fistulization through the skin. The patient presented positive BAAR in the drained fluid and Koch's bacillus in the urine. She was treated with a four-drug regimen (rifampicin, isoniazid, pyrazinamide, and etambutol), with great response and preserved graft function. We were informed that the recipient of the contralateral kidney also presented post-transplant TB, implying in a donor-derived origin. CONCLUSION: TB is an important differential diagnosis for infectious complications in patients after solid-organ transplantation, especially in endemic regions. Its initial clinical presentation can be unspecific and it should be suspected in the presence of fever or formation of fluid collections. The suspicion of TB is the key to early diagnosis and satisfactory outcomes in post-transplant TB.

Intracranial Malignant Peripheral Nerve Sheath Tumors Not Associated with a Cranial Nerve: Systematic Review and Illustrative Case.

OBJECTIVE: Primary intracranial malignant peripheral nerve sheath tumors (MPNSTs) not associated with cranial nerves are rare and aggressive neoplasms. The rarity of presentation has precluded rigorous analysis of diagnosis, risk factors, treatment, and survival. We analyzed every reported case through exhaustive literature review. In addition, we present our own experience managed with resection, radiotherapy, and first use of targeted therapy in a tumor of this type for a BRAF mutation identified during next-generation sequencing. METHODS: Two databases, PubMed and Embase, and crossed references were queried for intracranial MPNSTs not associated with a cranial nerve. Extracted variables included demographics, risk factors, tumor characteristics, interventions, and outcomes. Univariate and multivariate analysis was performed to identify factors with survival benefit. RESULTS: A total of 56 patients (including the present case) were included from 743 literature results. There was a male/female ratio of 1.5:1 and mean diagnosis age of 29.7 ± 21.8 years. Seventy-one percent of cases were sporadic and 23% neurofibromatosis type 1 related. Median survival was 29 ± 22.1 months with 1-year survival of 60%. Factors associated on univariate analysis with reduced survival were subtotal resection (P = 0.05), older age (P = 0.023), triton histology (P < 0.001), and early recurrence (≤6 months) (P = 0.018). On multivariate analysis, gross total resection reduced mortality risk (P = 0.011), whereas triton histology (P = 0.017) and infratentorial tumor location (P = 0.037) increased mortality. CONCLUSIONS: We present a systematic review of intracranial MPNSTs not associated with a cranial nerve. These tumors have poor prognosis and benefit from aggressive resection, multimodal treatment, and close follow-up. Next-generation sequencing can show molecular alterations for potential targeted therapy.

Combined Liver and Kidney Transplant in Acute Intermittent Porphyria: A Case Report.

BACKGROUND Acute intermittent porphyria is an inherited disease caused by a defect in heme biosynthesis, with accumulation of neurotoxic metabolites leading to acute neurovisceral symptoms. Some patients develop long-term neurological and renal damage after the acute episodes, many of them requiring hemodialysis. Since heme production in the human body occurs predominantly in the bone marrow and liver, liver transplantation has been shown to significantly reduce the production of neurotoxic metabolites, effectively controlling the disease. Patients with severe acute intermittent porphyria who have chronic kidney failure may benefit from combined kidney and liver transplant. Only 2 uses of this approach have been previously reported in the literature. CASE REPORT We report here the case of a 19-year-old male patient who received a combined liver and kidney transplant for the treatment of acute intermittent porphyria. He presented the first symptoms of the disease 4 years before the procedure, with abdominal pain and significant neurological impairment, with weakness requiring prolonged mechanical ventilation. He also had chronic kidney failure secondary to the porphyria. A combined liver and kidney transplant was performed, with no intraoperative complications. The explanted liver showed light siderosis, as well as portal and perisinusoidal fibrosis at microscopy. At 3.5 years of follow-up, he remains clinically well, with normal hepatic and renal function, had had no further acute porphyria episodes, and shows progressive neurological recovery. CONCLUSIONS This case demonstrates that combined liver and kidney transplant can be a curative treatment for patients with severe acute intermittent porphyria associated with end-stage renal failure. The patient shows satisfactory long-term function of both grafts, with no clinical or biochemical signs of porphyria recurrence.

Effects of Green Wheat (Triticum turgidum) and Common Wheat (Triticum aestivum) on the Metabolic Profile of Wistar Rats.

Studies have shown that the consumption of a diet containing whole grains may improve metabolic homeostasis and is related to the reduction of risk factors for the development of obesity, diabetes, cardiovascular diseases, and cancer. We aimed to investigate the effects of Triticum aestivum and Triticum turgidum on the metabolic profile of Wistar rats. Animals were divided into G1 (control group), G2 (T. turgidum), and G3 (T. aestivum). Anthropometric and biochemical parameters were evaluated after 45 days of treatment with both types of wheat. Our results showed that the use of the common or green wheat improved body weight percentage, visceral fat, glycemia, low-density lipoprotein cholesterol, triglycerides, and atherogenic indices such as atherogenic index, CCR1, and CCR2. Furthermore, wheat may also improve high-density lipoprotein cholesterol levels. The health-promoting properties of wheat occur probably due to the content of phytochemicals, antioxidants, and fibers. We suggest that the intake of T. aestivum and T. turgidum may be helpful in the prevention or treatment of obesity, diabetes and cardiovascular diseases.

Fatores de risco do diagnóstico de enfermagem: risco de infecção em pacientes com a Síndrome da Imunodeficiência Adquirida hospitalizados / Factores de riesgo del diagnóstico de enfermería: riesgo de infección en pacientes con el Síndrome de Inmunodeficiencia Adquirida hospitalizados / Risk factors of nursing diagnosis: risk of infection in patients with Acquired Immune Deficiency Syndrome hospitalized

Resumo O objetivo desta investigação é fue identificar na literatura os fatores de risco do diagnóstico de enfermagem Risco de Infecção presentes em pacientes com Síndrome da Imunodeficiência Adquirida hospitalizados. Trata-se de uma revisão integrativa, realizada nas bases de dados PubMed, SCOPUS, Cumulative Index to Nursing and Allied Health Literature, Literatura Latino-Americana em Ciências de Saúde, Scientific Electronic Library Online. Foram selecionados 10 artigos que atenderam aos critérios de inclusão. Identificaram-se estudos de casocontrole, ensaio clínico, transversal, coorte e descritivo. Os resultados evidenciaram cinco dos 19 fatores presentes no diagnóstico de enfermagem "Risco de infecção", indicados na North American Nursing Diagnosis Association, sendo eles: imunossupressão (considerado o mais prevalente, presente em 70% dos estudos), desnutrição, alteração do peristaltismo, procedimento invasivo e enfermidade crônica. Conclui-se que o conhecimento sobre os fatores de risco que uma população estudada está suscetível, oferece um norteamento para uma assistência direcionada e eficaz, uma série de riscos diferentes.

Resumen El objetivo de esta investigación fue identificar en la literatura los factores de riesgo del diagnóstico de enfermería Riesgo de Infección presentes en pacientes con Síndrome de Inmunodeficiencia Adquirida hospitalizados. Se trata de una revisión integrativa, realizada en las bases de datos PubMed, SCOPUS, Cumulative Index to Nursing and Allied Health Literature, Literatura Latinoamericana en Ciencias de la Salud, Scientific Electronic Library Online. Se seleccionaron 10 artículos que atendieron a los criterios de inclusión. Se identificaron estudios de caso-control, ensayo clínico, transversal, cohorte y descriptivo. Los resultados evidenciaron cinco de los 19 factores presentes en el diagnóstico de enfermería "Riesgo de infección", indicados en la North American Nursing Diagnosis Association, siendo ellos: inmunosupresión (considerado el más prevalente, presente en 70% de los estudios), desnutrición, alteración del peristaltismo, el procedimiento invasivo y la enfermedad crónica. Se concluye que el conocimiento sobre los factores de riesgo en la población estudiada es susceptible, por lo que se ofrece una guía para la asistencia dirigida y eficaz, a fin de reducir riesgos.

Abstract The aim of this research was to identify in the literature the risk factors of the Nursing Risk Assessment of Infection present in patients with Acquired Immune Deficiency Syndrome hospitalized. This is an integrative review, carried out in the PubMed, SCOPUS, Cumulative Index to Nursing and Allied Health Literature databases, Latin American Literature in Health Sciences, Scientific Electronic Library Online. We selected 10 articles that met the inclusion criteria. Case-control studies, clinical, transverse, cohort and descriptive studies were identified. Five of the 19 factors present in the nursing diagnosis "Risk of infection", indicated in the North American Nursing Diagnosis Association, were: immunosuppression (considered the most prevalent present in 70% of the studies), malnutrition, peristalsis, invasive procedure and chronic disease. It is concluded that the knowledge about the risk factors in the studied population is susceptible, so a guide is offered for targeted and effective assistance in order to reduce risks.

Espondilodiscite como complicação infecciosa de cateterismo cardíaco / Spondylodiscitis ss Infectious complication of cardiac catheterization

A espondilodiscite é a principal manifestação da osteomielite vertebral hematogênica em pacientes >50 anos, sendo o Staphylococcus aureus o agente envolvido na maioria dos casos. O diagnóstico clínico é dificultado pela inespecificidade dos sintomas e pela baixa incidência. Suas consequências podem ser desastrosas principalmente quando se compromete a coluna espinhal. Este relato apresenta caso de espondilodiscite por S. aureus após angioplastia coronariana percutânea.

Spondylodiscitis is the main manifestation of hematogenous vertebral osteomyelitis in patients over 50 years old, with Staphylococcus aureus the agent involved in most cases. Clinical diagnosis is complicated by nonspecific symptoms and low incidence. The consequences can be disastrous, especially when affecting the spine. This report presents a case of spondylodiscitis caused by S. aureus after percutaneous coronary angioplasty.