Surgical management of Rathke cleft cysts in pediatric patients: a single institution experience.

OBJECTIVE: Rathke cleft cysts (RCCs) are benign, epithelial-lined sellar lesions that arise from remnants of the craniopharyngeal duct. Due to their rarity in the pediatric population, data are limited regarding the natural history and optimal management of growing or symptomatic RCCs. We present our institutional experience with the surgical management of RCCs. METHODS: We performed a retrospective study of consecutive RCC patients ≤ 18 years old treated surgically at our institution between 2006 and 2022. RESULTS: Overall, 567 patients with a diagnosis of pituitary mass or cyst were identified. Of these, 31 had a histopathological diagnosis of RCC, 58% female and 42% male. The mean age was 13.2 ± 4.2 years. Presenting symptoms included headache (58%), visual changes (32%), and endocrinopathies or growth delay (26%); 13% were identified incidentally and subsequently demonstrated growth on serial imaging. Six percent presented with symptomatic intralesional hemorrhage. Surgical approach was transsphenoidal for 90% of patients and orbitozygomatic for 10%. Preoperative headaches resolved in 61% of patients and preoperative visual deficits improvement in 55% after surgery. New pituitary axis deficits were seen in 9.7% of patients. Only two complications occurred from a first-time surgery: one cerebrospinal fluid leak requiring lumbar drain placement, and one case of epistaxis requiring cauterization. No patients experienced new visual or neurological deficits. Patients were followed postoperatively with serial imaging at a mean follow-up was 62.9 ± 58.4 months. Recurrence requiring reoperation occurred in 32% of patients. Five-year progression-free survival was 47.9%. Except for one patient with multiple neurological deficits from a concurrent tectal glioma, all patients had a modified Rankin Scale score of 0 or 1 (good outcome) at last follow-up. CONCLUSION: Due to their secretory epithelium, pediatric RCCs may demonstrate rapid growth and can cause symptoms due to local mass effect. Surgical management of symptomatic or growing pediatric RCCs via cyst fenestration or partial resection of the cyst wall can be performed safely, with good neurologic outcomes. There is a nontrivial risk of endocrinologic injury, and long-term follow up is needed due to high recurrence rates.

Going the distance in acoustic neuroma resection: microsurgical outcomes at high-volume centers of excellence.

PURPOSE: High-volume hospitals are associated with improved surgical outcomes for acoustic neuromas (ANs). Due to the benign and slow-growing nature of ANs, many patients travel to geographically distant cities, states, or countries for their treatment. However, the impact of travel burden to high-volume centers, as well as its relative benefit are poorly understood. We compared post-operative outcomes between AN patients that underwent treatment at local, low-volume hospitals with those that traveled long distances to high-volume hospitals. METHODS: The National Cancer Database was used to analyze AN patients that underwent surgery (2004-2015). Patients in the lowest quartile of travel distance and volume (Short-travel/Low-Volume: STLV) were compared to patients in the highest quartile of travel distance and volume (Long-travel/High-Volume: LTHV). Only STLV and LTHV cases were included for analysis. RESULTS: Of 13,370 cases, 2,408 met inclusion criteria. STLV patients (n = 1,305) traveled a median of 6 miles (Interquartile range [IQR] 3-9) to low-volume centers (median 2, IQR 1-3 annual cases) and LTHV patients (n = 1,103) traveled a median of 143 miles [IQR 103-230, maximum 4,797] to high-volume centers (median 34, IQR 28-42 annual cases). LTHV patients had lower Charlson/Deyo scores (p = 0.001), mostly received care at academic centers (81.7% vs. 39.4%, p < 0.001), and were less likely to be minorities (7.0% vs. 24.2%, p < 0.001) or underinsured (4.2% vs. 13.8%, p < 0.001). There was no difference in average tumor size. On multivariable analysis, LTHV predicted increased likelihood of gross total resection (odds ratio [OR] 5.6, 95% confidence interval [CI] 3.8-8.4, p < 0.001), longer duration between diagnosis and surgery (OR 1.3, 95% CI 1.0-1.6, p = 0.040), decreased length of hospital stay (OR 0.5, 95% CI 0.4-0.7, p < 0.001), and greater overall survival (Hazard Ratio [HR] 0.6, 95% CI 0.4-0.95, p = 0.029). There was no significant difference in 30-day readmission on adjusted analysis. CONCLUSION: Although traveling farther to high-volume centers was associated with greater time between diagnosis and treatment for AN patients, they experienced superior postoperative outcomes compared to patients who received treatment locally at low-volume centers. Enabling access and travel to high-volume centers may improve AN patient outcomes.

Machine Learning to Predict Hearing Preservation After Middle Cranial Fossa Approach for Sporadic Vestibular Schwannomas.

OBJECTIVE: Predict hearing preservation after middle cranial fossa approach for vestibular schwannomas. STUDY DESIGN: Application of machine learning algorithms, including classification and regression trees and random forest models to observational data. SETTING: Single-tertiary referral center. PARTICIPANTS: Patients (n = 144) with a previously untreated sporadic vestibular schwannoma who underwent microsurgical resection by middle cranial fossa approach between November 2017 and November 2021. INTERVENTIONS: Middle cranial fossa approach. MAIN OUTCOME AND MEASURES: Hearing preservation, defined by postoperative word recognition score of 50% or greater and pure tone average below 50 dB HL or less than 10% reduction in word recognition score. Model performance was evaluated with classification accuracy in an independent validation sample. Variable importance for the random forest model is reported according to entropy, a measure of mean decrease in model accuracy incurred by excluding each variable from the model. RESULTS: Hearing preservation was achieved in 60% of patients (86 of 144) overall. The classification and regression tree model identified preoperative pure tone average with a cut point of 30 dB HL, and more posterior tumor position to be the most important prognostic features for hearing preservation. Model accuracy was 0.68. The random forest model demonstrated perfect accuracy (1). Baseline pure tone average, word recognition score, and anteroposterior tumor position were among the most influential features for hearing preservation prediction. CONCLUSION: Machine learning algorithms have the potential for accurate prediction of hearing preservation rates after middle fossa approach for vestibular schwannomas at a single institution. These models have the capacity for continued refinement with ongoing addition of data.

Ocular Syphilis Mimicking Giant Cell Arteritis.

Syphilis is a rare cause of vision loss that mostly occurs after an infection of the meninges, brain tissue, and parenchyma. Syphilis can mimic auto-immune disease like giant cell arteritis which also manifest as sudden vision loss. Spirochete Treponema pallidum can spread through sexual contact and cause painless ulcers. Spirochetes can disseminate systemically and lead to secondary syphilis. Ocular syphilis can affect all parts of the eye in secondary and tertiary stages. It can present as scleritis, inflammation of the optic nerve, and uveitis. We present the case of a 59- year-old male suffering from severe vision loss in the left eye and headache initially misdiagnosed with giant cell arteritis. He was correctly diagnosed with ocular syphilis after seeing a red macular rash on palms and soles, and was given penicillin G and probenecid. His visual acuity and field of vision improved soon. Ocular syphilis is usually diagnosed late or misdiagnosed and leads to irreversible vision loss. Physicians should keep in mind the possibility of ocular syphilis in patients presenting with a sudden loss of vision and severe headaches.

A Case of Bilateral Adrenal Hemorrhage: The Exceptional Cause of Adrenal Insufficiency.

Bilateral adrenal hemorrhage is an extremely uncommon and life-threatening condition. It is caused by multiple etiologies, including antiphospholipid syndrome, disseminated histoplasmosis, trauma, severe stress, and granulomatous disease. The authors present a unique case of a 64-year-old alcoholic male, who was admitted after fall and right hip fracture. On day seven of admission, the patient started to develop hypotension, leukocytosis, and tachycardia. CT abdomen was done, which ruled out infectious causes, however, it showed bilateral adrenal hemorrhages. Patient adrenocorticotrophic hormone (ACTH) stimulation test was positive for adrenal insufficiency and was started on hydrocortisone replacement. Our case highlights the fact that adrenal insufficiency after bilateral adrenal hemorrhage can be slow and can manifest as late as seven days and prompt therapy with steroids is warranted to avoid life-threatening adrenal insufficiency.

Quality of Life in Patients Undergoing Cardiac Surgery: Role of Coping Strategies.

Adaptive coping strategies are used to reduce stress in patients undergoing cardiac surgery. These strategies have a major role in physical health, psychological health, quality of life and also affect an individual's response to the disease. The current study was conducted to comprehend the impact of coping strategies on the quality of life of patients suffering from cardiac disease. A purposive convenient sampling method was used to collect data from different hospitals in South Punjab. We applied Carver's Brief Coping Orientation to Problem Experienced (Brief COPE) inventory and the WHO quality of life scale. A cross-sectional research design was proposed for the study. The findings of the study showed that coping strategies and quality of life are associated with each other, and the use of emotion-focused and problem-focused coping strategies have a significant impact on patients experiencing cardiac surgery. Demographic details of patients also revealed the differences in both variables. Implications and future recommendations have also been discussed.

Combined translabyrinthine, anterior petrosal approach for resection of collision vestibular schwannoma and petrous apex meningioma in neurofibromatosis type 2, with auditory brainstem implant placement.

The natural history of neurofibromatosis type 2 (NF2) is profound bilateral hearing loss. The decision to pursue microsurgery may be more complicated in NF2 than with sporadic tumors. Schwannomas in NF2 often occur with other skull base tumors. Treatment should be tailored to preserve auditory perception for as long as possible. The authors present the case of a man with NF2 and a vestibular schwannoma who has poor hearing on the same side as a large petrous apex meningioma, both opposite to a well-hearing ear. This case highlights surgical decision-making and technical nuances during resection of collision tumors in NF2. The video can be found here: https://stream.cadmore.media/r10.3171/2021.7.FOCVID21130.

Renal Infiltration as a Primary Presentation of Burkitt Lymphoma Secondary to Systemic Lupus Erythematosus: A Rarity Unto a Rarity.

Burkitt lymphoma (BL) is a highly aggressive non-Hodgkin B-cell lymphoma characterized by the translocation and deregulation of the MYC (MyeloCytomatosis) gene on chromosome 8. Three distinct clinical forms of BL are recognized: endemic (African), sporadic (non-endemic), and immunodeficiency-associated. Bilateral renal infiltration leading to acute kidney injury (AKI) is a rare initial presentation of BL. Diagnosis is usually made after evaluating the histology and immunophenotyping of the affected tissue. We report a case of a 46-year-old male who presented with symptoms of AKI resulting from infiltrative disease, a primary presentation of lymphoma. The patient was a known case of systemic lupus erythematosus (SLE) for the last five years and was referred to the nephrology department due to acute elevation in creatinine, from 0.8 mg/dL to 3.57 mg/dL. On physical examination, there was no lymphadenopathy. Nephrology and SLE workup revealed low complement protein levels and absolute neutrophils, lymphocytes, and metamyelocytes. Renal ultrasound (USG) showed both kidneys with symmetric and edematous appearance. Biopsy affirmed high-grade B-cell lymphoma, positive for BCL-6 (B-cell leukemia/lymphoma) and CD-10 (cell surface marker) and negative for BCL-2 (B-cell leukemia/lymphoma). PET (positron emission tomography) scan showed extensive hypermetabolic lymphadenopathy in multiple areas. The patient was started on chemotherapy and on continuous renal replacement therapy. He improved clinically, and his creatinine lowered down to 0.8 mg/dL. Repeat USG showed decreased edematous appearance of both kidneys. Primary renal infiltration by BL is a rare presentation in adults. Prompt renal biopsy will change the course of treatment and can affect the prognosis. It is thoroughly advised to keep this malignancy in mind when making a diagnosis for AKI.

Urinary Tract Infection Caused by the Novel Pathogen, Lactococcus Garvieae: A Case Report.

Lactococcus garvieae is a part of the genus Lactococcus which was previously a part of the genus Streptococcus. It has been associated with serious diseases in aquaculture. However, human infections are rare. The most common presentation in humans is infective endocarditis. Urinary tract infection (UTI) is a unique presentation of this pathogen. We report the case of a 70-year-old male with a past history of benign prostatic hyperplasia who presented with confusion. Urinalysis confirmed the growth of L. garvieae. A seven-day treatment course of amoxicillin-clavulanate successfully treated the patient. The risk factors for acquiring the L. garvieae infections include contact with seafood or aquaculture. Other risk factors include immunosuppression, gastric acid suppression, and anatomical or physiological defect in the gastrointestinal tract. Special tests, such as VITEK® 2, API® 32 strep system, 16S rRNA, or polymerase chain reaction (PCR) testing, are needed for its diagnosis. Hence, we suggest underreporting of the infection may be possible. It is a novel cause of UTI, we suggest a high index of suspicion should be kept, especially in people with associated risk factors or exposure to seafood.

Primary Cutaneous Nocardiosis: A Rare Presentation of Nocardiosis.

Nocardia is an uncommon gram-positive, weakly acid-fast bacterium that causes systemic or localized suppurative disease in humans and animals. Nocardiosis is typically regarded as an opportunistic infection, but approximately one-third of the patients are immunocompetent. The most common presentation is pulmonary disease (39%) followed by systemic involvement, defined as involvement of more than two sites; cutaneous presentation constitutes only 8% of the cases. Nocardia is widely distributed geographically; however, in the US, it is mostly found in warm and dry areas of South West and South East. We present a perfect case of cutaneous nocardiosis of a 70-year-old male, who presented with a traumatic splinter injury, leading to pustules formation on the right index finger, along with erythema and induration of the right arm. The patient was empirically diagnosed and treated for cellulitis, with amoxicillin and clavulanic acid, resulting in deterioration of the wound. The patient underwent incision and drainage and wound culture grew nocardia. The index of suspicion should be kept in mind while treating infectious blisters which have failed outpatient cellulitis treatment, immunocompromised hosts, and in nocardia prevalent regions.

Association Between Smoking and Survival Benefit of Immunotherapy in Advanced Malignancies: A Systematic Review and Meta-Analysis.

OBJECTIVES: Smoking is associated with an increased tumor mutational burden. As tumor mutational burden has been shown to correlate with response to immunotherapy (IO), we hypothesized that a history of smoking may be associated with better response to IO. METHODS: We utilized a systematic review with stratified meta-analysis of randomized clinical trials of IO versus standard of care in patients with advanced solid organ malignancies. RESULTS: Among 9 relevant studies, we found no significant difference in the benefit of IO, compared with other systemic therapies, between ever smokers (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.58-1.04; P=0.09) and never smokers (HR, 0.75; 95% CI, 0.67-0.86; P<0.0001) (test for difference P=0.83). We also observed no significant difference between current (HR, 0.92; 95% CI, 0.63-1.34; P=0.66; I=67%) and never smokers (HR, 0.74; 95% CI, 0.59-0.93; P=0.01; I=46%) (test for difference P=0.35). CONCLUSIONS: Stratified meta-analysis demonstrates that smoking status is not significantly associated with the response to IO in the treatment of advanced solid organ malignancies.

Diagnostic utility of restriction spectrum imaging (RSI) in glioblastoma patients after concurrent radiation-temozolomide treatment: A pilot study.

Discriminating between tumor recurrence and treatment effects in glioblastoma patients undergoing radiation-temozolomide (RT/TMZ) therapy remains a major clinical challenge. Here, we report a pilot study to determine the utility of restriction spectrum imaging (RSI), an advanced diffusion-weighted MRI (DWI) technique that affords meso-scale resolution of cell density, in this assessment. A retrospective review of 31 patients with glioblastoma treated between 2011 and 2017 who underwent surgical resection or biopsy over radiographic concern for tumor recurrence following RT/TMZ was performed. All patients underwent RSI prior to surgical resection. Diagnostic utility of RSI for tumor recurrence was determined in comparison to histopathology. Analysis of surgical specimens revealed treatment effects in 6/31 patients (19%) and tumor recurrence in 25/31 patients (81%). There was general concordance between the measured RSI signal and histopathologic diagnosis. RSI was negative in 5/6 patients (83%) in patients with histological evidence of treatment effects. RSI was positive in 21/25 patients (84%) in patients with tumor recurrence. The sensitivity, specificity, positive and negative predictive values of RSI for glioblastoma recurrence were 84%, 86%, 95%, and 60%, respectively. Histopathologic review showed agreement between the RSI signal and cellularity of the tumor specimen. These data support the use of RSI in the evaluation of treatment effects versus tumor recurrence in glioblastoma patients after RT-TMZ therapy.

A New Multi-Ingredient Recipe for the Treatment of Localized Advanced Periodontal Disease following the Surgical Removal of Impacted Wisdom Teeth.

Periodontal disease is a chronic inflammation of the tooth supporting structures. It leads to bone and attachment loss which is irreversible. Extraction of horizontally impacted lower third molar (L3M) teeth may result in localized periodontal pockets at the distal aspect of the adjacent lower second molars (L2M). We present a case of a 21-year-old male who suffered from a swelling and pain around his lower right second molar following surgical removal of a mesioangular impacted lower right third molar. We showed that oral hygiene measures, surgical access, mixture of autogenous and synthetic bone graft, and guided tissue regeneration (GTR) were enough to control the problem.

CCL2 and CCR2 are Essential for the Formation of Osteoclasts and Foreign Body Giant Cells.

Osteoclasts are multinucleated cells responsible for bone resorption. They are derived from the fusion of cells in the monocyte/macrophage lineage. Monocytes and macrophages can also fuse to form foreign body giant cells (FBGC). Foreign body giant cells are observed at the interface between a host and a foreign body such as implants during a foreign body reaction. Macrophages are attracted to the site of bone resorption and foreign body reactions by different cytokines. Chemokine (C-C) ligand-2 (CCL2) is an important chemotactic factor and binds to a receptor CCR2. In this study we investigated the importance of CCL2 and the receptor CCR2 in the formation of osteoclasts and FBGC. CCL2 mRNA was more highly expressed in giant cell culture than macrophages, being 9-fold and 16-fold more abundant in osteoclasts and FBGC respectively. Significantly fewer osteoclasts and FBGC were cultured from the bone marrow of CCL2 and CCR2 knockout mice, when compared to wild type. Not only were the number of giant cells reduced but there was a significant reduction in the number of nuclei and the size of these cells in the cultures of CCL2 and CCR2 knockout mice. Formation of osteoclasts and FBGC were recovered in cultures by addition of exogenous CCL2 to the media containing marrow cells from CCL2-/- mice. We conclude that CCL2 and its receptor CCR2 are important for the formation of osteoclasts and FBGC and absence of these genes causes inhibition of osteoclast and FBGC formation.

Enhancing dentate gyrus function with dietary flavanols improves cognition in older adults.

The dentate gyrus (DG) is a region in the hippocampal formation whose function declines in association with human aging and is therefore considered to be a possible source of age-related memory decline. Causal evidence is needed, however, to show that DG-associated memory decline in otherwise healthy elders can be improved by interventions that enhance DG function. We addressed this issue by first using a high-resolution variant of functional magnetic resonance imaging (fMRI) to map the precise site of age-related DG dysfunction and to develop a cognitive task whose function localized to this anatomical site. Then, in a controlled randomized trial, we applied these tools to study healthy 50-69-year-old subjects who consumed either a high or low cocoa flavanol-containing diet for 3 months. A high-flavanol intervention was found to enhance DG function, as measured by fMRI and by cognitive testing. Our findings establish that DG dysfunction is a driver of age-related cognitive decline and suggest non-pharmacological means for its amelioration.

Blood transfusions are associated with urinary biomarkers of kidney injury in cardiac surgery.

OBJECTIVE: Cardiac surgery is a major cause of acute kidney injury. In this setting, receipt of blood transfusions seems to be associated with a higher risk of acute kidney injury, as measured using serum creatinine values. We examined this association further by using urinary biomarkers of kidney injury. METHODS: A total of 1210 adults underwent cardiac surgery and were divided into 3 groups on the basis of the receipt of intraoperative packed red blood cell units: no blood (n = 894), 2 or less packed red blood cell units (n = 206), and more than 2 packed red blood cell units (n = 110). Acute kidney injury was defined as (1) doubling of serum creatinine from the preoperative value; (2) first postoperative urinary interleukin-18 in the fifth quintile; and (3) first postoperative urinary neutrophil gelatinase-associated lipocalin in the fifth quintile. We determined the relative risk for acute kidney injury outcome according to packed red blood cell units group after adjusting for 12 preoperative and surgical variables. By using the Sobel test for mediation analysis, we also evaluated the role of biomarkers in causing acute kidney injury through alternative pathways. RESULTS: Acute kidney injury was more common in those who received more than 2 packed red blood cell units. In patients receiving more than 2 packed red blood cell units, the adjusted relative risks were 2.3 (95% confidence interval, 1.2-4.4, P .01), 1.36 (95% confidence interval, 1.0-1.9, P .05), and 1.34 (95% confidence interval, 1.0-1.8, P .06) for doubling of serum creatinine, urinary interleukin-18 in the fifth quintile (>60 pg/mL), and urinary neutrophil gelatinase-associated lipocalin in the fifth quintile (>102 ng/mL), respectively. Furthermore, the effect of packed red blood cell units transfusion on acute kidney injury was partially mediated by interleukin-18. CONCLUSIONS: Receipt of 2 or more packed red blood cell units during cardiac surgery is associated with a greater risk of acute kidney injury defined by serum creatinine and kidney injury biomarkers.

Differential expression of chemokines, chemokine receptors and proteinases by foreign body giant cells (FBGCs) and osteoclasts.

Osteoclasts and foreign body giant cells (FBGCs) are both derived from the fusion of macropahges. These cells are seen in close proximity during foreign body reactions, therefore it was assumed that they might interact with each other. The aim was to identify important genes that are expressed by osteoclasts and FBGCs which can be used to understand peri-implantitis and predict the relationship of these cells during foreign body reactions. Bone marrow macrophages (BMM) were treated with receptor activator of nuclear factor kappa B ligand (RANKL) to produce osteoclasts. Quantitative PCR (qPCR) was used to identify the genes that were expressed by osteoclasts and FBGCs compared to macrophage controls. TRAP staining was used to visualise the cells while gelatine zymography and western blots were used for protein expression. Tartrate-resistant acid phosphatase (TRAP), matrix metallo proteinase 9 (MMP9), nuclear factor of activated T cells 1 (NFATc1), cathepsin K (CTSK) and RANK were significantly lower in FBGCs compared to osteoclasts. Inflammation specific chemokines such as monocyte chemotactic protein (MCP1 also called CCL2), macrophage inflammatory protein 1 alpha (MIP1α), MIP1ß and MIP1γ, and their receptors CCR1, CCR3 and CCR5, were highly expressed by FBGCs. FBGCs were negative for osteoclast specific markers (RANK, NFATc1, CTSK). FBGCs expressed chemokines such as CCL2, 3, 5 and 9 while osteoclasts expressed the receptors for these chemokines i.e. CCR1, 2 and 3. Our findings show that osteoclast specific genes are not expressed by FBGCs and that FBGCs interact with osteoclasts during foreign body reaction through chemokines.

Molecular drivers and cortical spread of lateral entorhinal cortex dysfunction in preclinical Alzheimer's disease.

The entorhinal cortex has been implicated in the early stages of Alzheimer's disease, which is characterized by changes in the tau protein and in the cleaved fragments of the amyloid precursor protein (APP). We used a high-resolution functional magnetic resonance imaging (fMRI) variant that can map metabolic defects in patients and mouse models to address basic questions about entorhinal cortex pathophysiology. The entorhinal cortex is divided into functionally distinct regions, the medial entorhinal cortex (MEC) and the lateral entorhinal cortex (LEC), and we exploited the high-resolution capabilities of the fMRI variant to ask whether either of them was affected in patients with preclinical Alzheimer's disease. Next, we imaged three mouse models of disease to clarify how tau and APP relate to entorhinal cortex dysfunction and to determine whether the entorhinal cortex can act as a source of dysfunction observed in other cortical areas. We found that the LEC was affected in preclinical disease, that LEC dysfunction could spread to the parietal cortex during preclinical disease and that APP expression potentiated tau toxicity in driving LEC dysfunction, thereby helping to explain regional vulnerability in the disease.

Towards more accurate microcavity sensors: maximum likelihood estimation applied to a combination of quality factor and wavelength shifts.

Optical microcavities are widely used for biological and chemical sensing applications. In these devices, a sensing event is estimated by measuring the shift in the resonant wavelength, or in the quality factor of the microcavity. However, all published works to date only use one of these measures to estimate the sensing event. Here, we show that the estimation accuracy of a sensing event can be improved by employing a combination of both the quality factor and the resonant wavelength measurements in a microcavity sensor. We further demonstrate an experimental application of this model by introducing a refractive index change for a microtoroidal cavity sensor immersed in a liquid. By further using the finite element method simulations in conjunction with the estimator model, we show the existence of three distinct measurement regimes as a function of the quality factor of the microcavity. Finally, the estimator model is extended to develop a sensing metric to compare performance of optical or non-optical sensors.

Prevention of chronic kidney disease and subsequent effect on mortality: a systematic review and meta-analysis.

OBJECTIVES: To perform a systematic review of randomized controlled trials to determine whether prevention or slowing of progression of chronic kidney disease would translate into improved mortality, and if so, the attributable risk due to CKD itself on mortality. BACKGROUND: CKD is associated with increased mortality. This association is largely based on evidence from the observational studies and evidence from randomized controlled trials is lacking. METHODS: We searched Ovid, Medline and Embase for RCTs in which an intervention was given to prevent or slow the progression of CKD and mortality was reported as primary, secondary or adverse outcomes were eligible and selected. For the first phase, pooled relative risks for renal endpoints were assessed. For the second phase, we assessed the effect on mortality in trials of interventions that definitively reduced CKD endpoints. RESULTS: Among 52 studies selected in first phase, only renin-angiotensin-aldosterone-system blockade vs. placebo (n = 18 trials, 32,557 participants) met the efficacy criteria for further analysis in the second phase by reducing renal endpoints 15 to 27% compared to placebo. There was no difference in all-cause mortality (RR 0.99, 95% CI 0.92 to 1.08) or CV death (RR 0.97, 95% CI 0.78 to 1.21) between the treatment and control groups in these trials. There was sufficient statistical power to detect a 9% relative risk reduction in all-cause mortality and a 14% relative risk reduction in cardiovascular mortality. CONCLUSIONS: Firm evidence is lacking that prevention of CKD translates into reductions in mortality. Larger trials with longer follow-up time are needed to determine the benefit of CKD prevention on survival.