Prevalence of kidney health genetic variants in adults with sickle cell nephropathy.

The pathophysiology and genetic risk for sickle cell disease (SCD)-related chronic kidney disease (CKD) are not well understood. In 70 adults with SCD-related CKD and without APOL1 inherited in a high-risk pattern, 24 (34%) had pathogenic variants in candidate genes using KidneySeq™. A moderate impact INF2 variant was observed in 20 (29%) patients and those with 3 versus 0-2 pathogenic or moderate impact glomerular genetic variants had higher albuminuria and lower estimated glomerular filtration rate (adjusted p ≤ 0.015). Using a panel of preselected genes implicated in kidney health, we observed several variants in people with sickle cell nephropathy.

Soluble urokinase plasminogen activator receptor is associated with kidney disease and its progression in sickle cell anemia.

Not available.

Antibody-mediated rejection in pediatric kidney transplant recipients: A report from the Pediatric Nephrology Research Consortium.

BACKGROUND: Antibody-mediated rejection (AMR) is a major cause of kidney allograft loss. There is a paucity of large-scale pediatric-specific data regarding AMR treatment outcomes. METHODS: Data were obtained from 14 centers within the Pediatric Nephrology Research Consortium. Kidney transplant recipients aged 1-18 years at transplant with biopsy-proven AMR between 2009 and 2019 and at least 12 months of follow-up were included. The primary outcome was graft failure or an eGFR <20 mL/min/1.73 m2 at 12 months following AMR treatment. AMR treatment choice, histopathology, and DSA class were also examined. RESULTS: We reviewed 123 AMR episodes. Median age at diagnosis was 15 years at a median 22 months post-transplant. The primary outcome developed in 27.6%. eGFR <30 m/min/1.73 m2 at AMR diagnosis was associated with a 5.6-fold higher risk of reaching the composite outcome. There were no significant differences in outcome by treatment modality. Histopathology scores and DSA class at time of AMR diagnosis were not significantly associated with the primary outcome. CONCLUSIONS: In this large cohort of pediatric kidney transplant recipients with AMR, nearly one-third of patients experienced graft failure or significant graft dysfunction within 12 months of diagnosis. Poor graft function at time of diagnosis was associated with higher odds of graft failure.

Kidney failure outcomes in children and young adults with sickle cell disease in the United States Renal Data System.

BACKGROUND: Children and young adults with sickle cell disease (SCD) develop kidney disease early in childhood, with some patients progressing to require dialysis and kidney transplantation. The prevalence and outcomes of children with kidney failure (chronic kidney disease stage 5) due to SCD are not well described. This study aimed to assess the outcome of children and young adults with SCD with kidney failure compared to matched children and young adults without SCD with kidney failure in a large national database. METHODS: Utilizing the United States Renal Data System (USRDS), we retrospectively examined kidney failure outcomes in children and young adults with SCD from 1998 to 2019. RESULTS: We identified 97 patients with SCD who developed kidney failure and identified 96 matched controls with a median age of 19 years (IQR 17, 21) at the time of kidney failure diagnosis. SCD patients had significantly shorter survival (8.4 years vs. 14.0 years, p < 0.001) and had a longer waiting time for their first transplant when compared to matched non-SCD kidney failure patients (12.1 years vs. 7.3 years, p < 0.001). CONCLUSIONS: Children and young adults with SCD kidney failure have significantly higher mortality when matched to non-SCD kidney failure children and experience a longer mean time to kidney transplant.

Primary papillary epithelial tumor of the sella: a case report of an emerging tumor type.

Primary papillary epithelial tumor of the sella (PPETS) is a newly described tumor entity with prototypical location in the sella. Only two case series with ten cases have been described so far. These tumours have a typical papillary architecture with bland nuclear features, TTF-1 immunopositivity and low MIB-1-labelling index. Many of these tumours were previously assigned under the category of 'ectopic choroid plexus papilloma'. PPETS expands the group of TTF-1 positive tumours of the central nervous system. Histomorphology plays an essential role in making this diagnosis. We report a case of 44-year-old female with a sellar mass lesion, who presented with progressive loss of vision and diagnosed as primary papillary epithelial tumor.

Association of Cerebrovascular Injury and Secondary Vascular Insult With Poor Outcomes After Gunshot Wound to the Head in a Large Civilian Population.

BACKGROUND AND OBJECTIVES: Cerebrovascular injury (CVI) after civilian gunshot wound to the head (GSWH) likely contributes to poor outcomes, but little supporting evidence exists. The purpose of this study was to determine whether intracranial CVI from GSWH and secondary vascular insult (stroke or rehemorrhage) were associated with poor outcomes in a large civilian population. METHODS: This was a single-institution, retrospective cohort study on patients admitted between January 2014 and July 2022 at a large, metropolitan, level-1 trauma center. Multivariate regression models and propensity score matching were used. RESULTS: A total of 512 civilian patients presented with GSWH, and a cohort of 172 (33.5%) met inclusion criteria, with 143 (83.1%) males and a mean (SD) age of 34.3 (±14.2) years. The incidence of intracranial CVI was 50.6% (87/172 patients), and that of secondary vascular insult was 32.2% (28/172 patients). Bifrontal trajectories (adjusted odds ratio [aOR] 13.11; 95% CI 2.45-70.25; P = .003) and the number of lobes traversed by the projectile (aOR 3.18; CI 1.77-5.71; P < .001) were associated with increased odds of resultant CVI. Patients with CVI suffered higher rate of mortality (34% vs 20%; odds ratio [OR] 2.1; CI 0.78-5.85; P = .015) and were less likely to achieve a good functional outcome with a Glasgow Outcome Score of 4-5 (34% vs 68%; OR 0.24; CI 0.1-0.6; P = .004) at follow-up. Furthermore, patients with CVI and resultant secondary vascular insult had even worse functional outcomes (Glasgow Outcome Score 4-5, 16.7% vs 39.0%; aOR 0.012; CI 0.001-0.169, P = .001). CONCLUSION: Intracranial CVI from GSWH and associated secondary vascular insult are associated with poor outcomes. Given the high prevalence and potentially reversible nature of these secondary injuries, early screening with vascular imaging and treatment of underlying CVI may prove to be critical to improve outcomes by reducing stroke and rehemorrhage incidence.

Machine Learning Predicts Acute Kidney Injury in Hospitalized Patients with Sickle Cell Disease.

INTRODUCTION: Acute kidney injury (AKI) is common among hospitalized patients with sickle cell disease (SCD) and contributes to increased morbidity and mortality. Early identification and management of AKI is essential to preventing poor outcomes. We aimed to predict AKI earlier in patients with SCD using a machine-learning model that utilized continuous minute-by-minute physiological data. METHODS: A total of6,278 adult SCD patient encounters were admitted to inpatient units across five regional hospitals in Memphis, TN, over 3 years, from July 2017 to December 2020. From these, 1,178 patients were selected after filtering for data availability. AKI was identified in 82 (7%) patient encounters, using the 2012 Kidney Disease Improving Global Outcomes (KDIGO) criteria. The remaining 1,096 encounters served as controls. Features derived from five physiological data streams, heart rate, respiratory rate, and blood pressure (systolic, diastolic, and mean), captured every minute from bedside monitors were used. An XGBoost classifier was used for classification. RESULTS: Our model accurately predicted AKI up to 12 h before onset with an area under the receiver operator curve (AUROC) of 0.91 (95% CI [0.89-0.93]) and up to 48 h before AKI with an AUROC of 0.82 (95% CI [0.80-0.83]). Patients with AKI were more likely to be female (64.6%) and have history of hypertension, pulmonary hypertension, chronic kidney disease, and pneumonia than the control group. CONCLUSION: XGBoost accurately predicted AKI as early as 12 h before onset in hospitalized SCD patients and may enable the development of innovative prevention strategies.

Sickle Cell Disease and CKD: An Update.

BACKGROUND: Sickle cell disease is an inherited red blood cell disorder that affects approximately 100,000 people in the USA and 25 million people worldwide. Vaso-occlusion and chronic hemolysis lead to dysfunction of vital organ systems, with the kidneys being among the most commonly affected organs. SUMMARY: Early renal manifestations include medullary ischemia with the loss of urine-concentrating ability and hyperfiltration. This can be followed by progressive damage characterized by persistent albuminuria and a decline in the estimated glomerular filtration rate. The risk of sickle nephropathy is greater in those with the APOL1 G1 and G2 kidney risk variants and variants in HMOX1 and lower in those that coinherit α-thalassemia. Therapies to treat sickle cell disease-related kidney damage focus on sickle cell disease-modifying therapies (e.g., hydroxyurea) or those adopted from the nonsickle cell disease kidney literature (e.g., renin-angiotensin-aldosterone system inhibitors), although data on their clinical efficacy are limited to small studies with short follow-up periods. Kidney transplantation for end-stage kidney disease improves survival compared to hemodialysis but is underutilized in this patient population. KEY MESSAGES: Kidney disease is a major contributor to early mortality, and more research is needed to understand the pathophysiology and develop targeted therapies to improve kidney health in sickle cell disease.

Validation of a prediction system for risk of kidney allograft failure in pediatric kidney transplant recipients: An international observational study.

Predicting long-term kidney allograft failure is an unmet need for clinical care and clinical trial optimization in children. We aimed to validate a kidney allograft failure risk prediction system in a large international cohort of pediatric kidney transplant recipients. Patients from 20 centers in Europe and the United States, transplanted between 2004 and 2017, were included. Allograft assessment included estimated glomerular filtration rate, urine protein-to-creatinine ratio, circulating antihuman leukocyte antigen donor-specific antibody, and kidney allograft histology. Individual predictions of allograft failure were calculated using the integrative box (iBox) system. Prediction performances were assessed using discrimination and calibration. The allograft evaluations were performed in 706 kidney transplant recipients at a median time of 9.1 (interquartile range, 3.3-19.2) months posttransplant; mean estimated glomerular filtration rate was 68.7 ± 28.1 mL/min/1.73 m2, and median urine protein-to-creatinine ratio was 0.1 (0.0-0.4) g/g, and 134 (19.0%) patients had antihuman leukocyte antigen donor-specific antibodies. The iBox exhibited accurate calibration and discrimination for predicting the outcomes up to 10 years after evaluation, with a C-index of 0.81 (95% confidence interval, 0.75-0.87). This study confirms the generalizability of the iBox to predict long-term kidney allograft failure in children, with performances similar to those reported in adults. These results support the use of the iBox to improve patient monitoring and facilitate clinical trials in children.

Magnetic Resonance Imaging Evaluation of Common Spinal Intramedullary Tumours: Ependymoma and Astrocytoma.

This cross-sectional study was carried out in the Department of Radiology and Imaging, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, from January 2015 to June 2016 in collaboration with Department of Neurosurgery and Department of Pathology of same hospital, to assess MRI findings of common IMSCTs and to find out the validity of MRI in the diagnosis of spinal ependymoma and astrocytoma, thereby differentiating these two common intramedullary entities. For this purpose, 40 patients aged from 15 to 60 years, who were diagnosed or suspected cases of having intramedullary spinal cord tumours were enrolled. These patients underwent preoperative MRI for evaluation of the spinal cord tumours during the study period in department of Radiology and Imaging. Also, patients were diagnosed by MRI as having IMSCTs incidentally was included. All of them were followed by histopathological examination of the same lesions after surgery. Among these 40 patients after exclusion for valid reason 28 cases were included as study population. MR images were obtained on a 1.5 Tesla (Avanto Magnatom, Siemens) unit with a spine surface coil. MRI findings were compared with histopathology after surgery keeping histopathology as gold standard. Out of 28 clinically and MRI diagnosed IMSCTs cases, 19 cases of ependymoma, 8 cases of astrocytoma and one diagnosed as hemangioblastoma by MRI. The mean age was 34.11±9.55 years, ranging from 15 to 56 years for ependymoma, 26.88±8.08 years ranging from 16 to 44 years for astrocytoma. Highest incidence (47.4%) was in between 31 to 40 years for ependymoma, 50.0% were in between 21-30 for Astrocytoma. On MRI majority 12(63.2%) of the cord ependymomas and majority 5(62.5%) of astrocytomas were in cervical region. While considering axial location ependymomas are mostly 17(89.5%) central and astrocytomas 5(62.5%) are eccentric in location. It was observed that out of 19 cases of ependymoma more than half 10(52.6%) had elongated shape, 12(63.1%) had well defined margin. Associated syringohydromyelia was present in 16(84.2%) cases. On T1WI 11(57.9%) and 8(42.1%) cases were iso and hypo respectively. On T2WI 14(73.7%) cases were hyper intense. After Gd-DTPA in most cases, 13(68.4%) cases showed diffuse enhancement. Noticeable and sizeable solid component observed among 13(68.4%) of the cases. Hemorrhage with cap sign was found in more than one third 7(36.8%) cases. Out of 8 cases of astrocytomas 4(50.0%) had lobulated shape, ill-defined margin 5(62.5%). T1WI: Iso 5(62.5%), hypo 3(37.5%), T2WI: hyper 5(62.5%), After Gd-DTPA: focal and heterogenous enhancement 3(37.5%) and rim enhancement 4(50.0%). Component: mixed 4(50.0%), cystic 3(37.5%) and solid 1(12.5%). Hemorrhage without cap sign 2(25.0%), associated syringohydromyelia 1(12.5%). In the case of evaluation of intramedullary ependymoma sensitivity of MRI in the present series is 94.44%, specificity 80.0%, Positive predictive value (PPV) 89.5%, Negative predictive value (NPV) 88.9% and accuracy 89.28%. In case of MRI evaluation of intramedullary astrocytoma sensitivity of MRI in the present study is 85.71%, specificity 90.47%, PPV 75%, NPV 95% and accuracy 89.2%. Thus present study shows MRI is a sensitive and effective noninvasive imaging modality in diagnosing common intramedullary spinal cord tumours.

Anatomical step-by-step dissection of common approaches to the third ventricle for trainees: surgical anatomy of the anterior transcortical and interhemispheric transcallosal approaches, surgical principles, and illustrative pediatric cases.

PURPOSE: To create a high-quality, cadaver-based, operatively oriented resource documenting the anterior transcortical and interhemispheric transcallosal approaches as corridors to the third ventricle targeted towards neurosurgical trainees at all levels. METHODS: Two formalin-fixed, latex-injected specimens were dissected under microscopic magnification and endoscopic-assisted visualization. Dissections of the transcortical and transcallosal craniotomies with transforaminal, transchoroidal, and interforniceal transventricular approaches were performed. The dissections were documented in a stepwise fashion using three-dimensional photographic image acquisition techniques and supplemented with representative cases to highlight pertinent surgical principles. RESULTS: The anterior transcortical and interhemispheric corridors afford excellent access to the anterior two-thirds of the third ventricle with varying risks associated with frontal lobe versus corpus callosum disruption, respectively. The transcortical approach offers a more direct, oblique view of the ipsilateral lateral ventricle, whereas the transcallosal approach readily establishes biventricular access through a paramedian corridor. Once inside the lateral ventricle, intraventricular angled endoscopy further enhances access to the extreme poles of the third ventricle from either open transcranial approach. Subsequent selection of either the transforaminal, transchoroidal, or interforniceal routes can be performed through either craniotomy and is ultimately dependent on individual deep venous anatomy, the epicenter of ventricular pathology, and the concomitant presence of hydrocephalus or embryologic cava. Key steps described include positioning and skin incision; scalp dissection; craniotomy flap elevation; durotomy; transcortical versus interhemispheric dissection with callosotomy; the aforementioned transventricular routes; and their relevant intraventricular landmarks. CONCLUSIONS: Approaches to the ventricular system for maximal safe resection of pediatric brain tumors are challenging to master yet represent foundational cranial surgical techniques. We present a comprehensive operatively oriented guide for neurosurgery residents that combines stepwise open and endoscopic cadaveric dissections with representative case studies to optimize familiarity with third ventricle approaches, mastery of relevant microsurgical anatomy, and preparation for operating room participation.

End Stage Kidney Disease Outcomes in Children and Young Adults with Sickle Cell Disease in the United States Renal Data System.

Background: Children and young adults with sickle cell disease (SCD) develop kidney disease early in childhood with some patients progressing to require dialysis and kidney transplantation. The prevalence and outcomes of children with end stage kidney disease (ESKD) due to SCD is not well described. This study aimed to assess the burden and outcomes of ESKD in children and young adults with SCD in a large national database. Methods: Utilizing the United States Renal Data System (USRDS) we retrospectively examined ESKD outcomes in children and young adults with SCD from 1998 - 2019. Results: We identified 97 patients with SCD that developed ESKD and identified 96 matched controls with median age of 19 years (IQR 17, 21) at time of ESKD diagnosis. SCD patients had significantly shorter survival (7.0 years vs. 12.4 years, p < 0.001) and had a longer waiting time to their first transplant when compared to matched non-SCD-ESKD patients (10.3 years vs. 5.6 years, p < 0.001). Conclusions: Children and young adults with SCD-ESKD have a significantly higher mortality when matched to non-SCD-ESKD children and experience a longer mean time to kidney transplant.

An automated histological classification system for precision diagnostics of kidney allografts.

For three decades, the international Banff classification has been the gold standard for kidney allograft rejection diagnosis, but this system has become complex over time with the integration of multimodal data and rules, leading to misclassifications that can have deleterious therapeutic consequences for patients. To improve diagnosis, we developed a decision-support system, based on an algorithm covering all classification rules and diagnostic scenarios, that automatically assigns kidney allograft diagnoses. We then tested its ability to reclassify rejection diagnoses for adult and pediatric kidney transplant recipients in three international multicentric cohorts and two large prospective clinical trials, including 4,409 biopsies from 3,054 patients (62.05% male and 37.95% female) followed in 20 transplant referral centers in Europe and North America. In the adult kidney transplant population, the Banff Automation System reclassified 83 out of 279 (29.75%) antibody-mediated rejection cases and 57 out of 105 (54.29%) T cell-mediated rejection cases, whereas 237 out of 3,239 (7.32%) biopsies diagnosed as non-rejection by pathologists were reclassified as rejection. In the pediatric population, the reclassification rates were 8 out of 26 (30.77%) for antibody-mediated rejection and 12 out of 39 (30.77%) for T cell-mediated rejection. Finally, we found that reclassification of the initial diagnoses by the Banff Automation System was associated with an improved risk stratification of long-term allograft outcomes. This study demonstrates the potential of an automated histological classification to improve transplant patient care by correcting diagnostic errors and standardizing allograft rejection diagnoses.ClinicalTrials.gov registration: NCT05306795 .

Mapping the conformational landscape of the stimulatory heterotrimeric G protein.

Heterotrimeric G proteins serve as membrane-associated signaling hubs, in concert with their cognate G-protein-coupled receptors. Fluorine nuclear magnetic resonance spectroscopy was employed to monitor the conformational equilibria of the human stimulatory G-protein α subunit (Gsα) alone, in the intact Gsαß1γ2 heterotrimer or in complex with membrane-embedded human adenosine A2A receptor (A2AR). The results reveal a concerted equilibrium that is strongly affected by nucleotide and interactions with the ßγ subunit, the lipid bilayer and A2AR. The α1 helix of Gsα exhibits significant intermediate timescale dynamics. The α4ß6 loop and α5 helix undergo membrane/receptor interactions and order-disorder transitions respectively, associated with G-protein activation. The αN helix adopts a key functional state that serves as an allosteric conduit between the ßγ subunit and receptor, while a significant fraction of the ensemble remains tethered to the membrane and receptor upon activation.

Evaluation of Long-Term Follow-Up in Ecchordosis Physaliphora versus Chordoma.

OBJECTIVE: Ecchordosis physaliphora (EP) is a non-neoplastic notochord remnant with limited literature. We present a review on surgically resected clival EP to evaluate if available follow-up is adequate to distinguish EP from chordomas. METHODS: A systematic literature review was completed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Case reports or series of adults with histopathologic and radiographic findings of surgically resected EP were included. Articles including pediatric patients, systematic reviews, chordomas, and without microscopic or radiographic confirmation, or the surgical approach, were excluded. Corresponding authors were contacted twice to further evaluate outcomes. RESULTS: Eighteen articles were included (n = 25 patients; mean age 47.5 years ± 12.6 [standard deviation] months). All patients had symptomatic, surgically resected EP, with cerebrospinal fluid leak or rhinorrhea the most common symptom (48%). All but 3 had gross total resection, with endoscopic endonasal transsphenoidal transclival the most common approach (80%). All but 3 reported immunohistochemistry findings, with physaliphorous cells the most common. All but 5 patients had definitive follow-up (80%), with average of 19.5 ± 17.2 months. One corresponding author reported longer-term follow-up for 1 patient (57 months). No recurrence or malignant transformation was reported. Mean time to clival chordoma recurrence (53.9 ± 26.8 months) was also evaluated in a review of 8 studies. CONCLUSIONS: Mean follow-up for resected EP was almost 3 times shorter than mean time to recurrence of chordomas. Available literature is likely inadequate to confirm the suspected benign nature of EP especially in reference to chordoma, precluding treatment and follow-up recommendations.

Heterogeneity of outcome measures in the clinical trials of treatment for oral submucous fibrosis-Systematic review.

OBJECTIVE: This systematic review was performed to evaluate the range of outcome measures used in interventional trials for oral submucous fibrosis (OSF). MATERIALS AND METHODS: PubMed, Scopus, and Cochrane databases were searched to identify randomized controlled trials (RCTs) published from 2004 to 2018 about OSF treatment. All the outcome measures and measurement methods mentioned in the trials were extracted and analyzed. RESULTS: Out of 120 published papers, 12 RCTs that met the inclusion criteria were included. A total of 38 single outcome measures and 29 composite outcome measures were considered under four different outcome domains, of which clinical symptoms and clinical response were the most commonly used. The linear measurement of mouth opening (11 trials; 91.66%) and Visual Analogue Scale (10 trials, 83.33%) were the predominant measurement methods. CONCLUSIONS: This systematic review highlights the high heterogeneity in outcome measures in therapeutic RCTs of OSF. This lack of widely agreed standard outcome measures in OSF is a great concern as it prevents the comparison of studies and meta-analyses to gather evidence. There is a dire need of establishing a core outcome set for reporting in the future clinical trials that may help facilitate treatment choice for OSF to improve life quality of patients.

Surgery for acromegaly: Indications and goals.

Acromegaly is a disease that occurs secondary to high levels of GH, most often from a hormone-secreting pituitary adenoma, with multisystem adverse effects. Diagnosis includes serum GH and IGF-1 levels, and obtaining an MRI pituitary protocol to assess for a functional pituitary adenoma. Attempted gross total resection of the GH-secreting adenoma is the gold standard in treatment for patients with acromegaly for a goal of biochemical remission. Medical and radiation therapies are available when patients do not achieve biochemical cure after surgical therapy.

A Deadly Herbicide 'Paraquat Poisoning' and Miserable Death of a 19 Years Boy.

Poisoning by paraquat herbicide now a days is a major medical problem in many parts of Asia as well as in Bangladesh. Already it has been banned in the European Union and some other countries for several years. Paraquat is highly toxic if ingested, with clinical features including oral burns, sore throat, vomiting and diarrhoea, progressing to pneumonitis, pulmonary fibrosis and multi-organ failure. Recently we dealt with many cases of paraquat poisoning in Mymensingh Medical College Hospital and here we report one case. A 19 years old student intentionally ingested 10 ml of paraquat herbicide and presented with multi organ failure. His renal function was supported with 4 session's hemodialysis and regain normal renal function. But he also developed Acute Lung Injury (ALI) and liver dysfunction, was supported with ionotropic and invasive ventilation and couldn't save. On 14th day of poisoning he died.