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Nature Protocols Nov 2023Kidney organoids derived from human pluripotent stem cells (hPSCs) are now being used as models of renal disease and nephrotoxicity screening. However, the proximal... (Review)
Review
Kidney organoids derived from human pluripotent stem cells (hPSCs) are now being used as models of renal disease and nephrotoxicity screening. However, the proximal tubules (PTs), which are responsible for most kidney reabsorption functions, remain immature in kidney organoids with limited expression of critical transporters essential for nephron functionality. Here, we describe a protocol for improved specification of nephron progenitors from hPSCs that results in kidney organoids with elongated proximalized nephrons displaying improved PT maturity compared with those generated using standard kidney organoid protocols. We also describe a methodology for assessing the functionality of the PTs within the organoids and visualizing maturation markers via immunofluorescence. Using these assays, PT-enhanced organoids display increased expression of a range of critical transporters, translating to improved functionality measured by substrate uptake and transport. This protocol consists of an extended (13 d) monolayer differentiation phase, during which time hPSCs are exposed to nephron progenitor maintenance media (CDBLY2), better emulating human metanephric progenitor specification in vivo. Following nephron progenitor specification, the cells are aggregated and cultured as a three-dimensional micromass on an air-liquid interface to facilitate further differentiation and segmentation into proximalized nephrons. Experience in culturing hPSCs is required to conduct this protocol and expertise in kidney organoid generation is advantageous.
Topics: Humans; Cell Culture Techniques; Kidney; Pluripotent Stem Cells; Nephrons; Cell Differentiation; Organoids
PubMed: 37770563
DOI: 10.1038/s41596-023-00880-1 -
Clinics in Colon and Rectal Surgery Jan 2023Many surgeons tend to overuse proximal fecal diversion in the setting of colonic surgery. The decision to proximally divert an anastomosis should be made with careful... (Review)
Review
Many surgeons tend to overuse proximal fecal diversion in the setting of colonic surgery. The decision to proximally divert an anastomosis should be made with careful consideration of the risks and benefits of proximal diversion. Proximal diversion does not decrease the rate of anastomotic leak, but it does decrease the severity of leaks. Anastomotic height for low pelvic anastomoses, hemodynamic instability, steroid use, male sex, obesity, malnutrition, smoking, and alcohol abuse increase the rate of anastomotic leak. Biologics, most immunosuppressive agents, unprepped colons, and radiation for rectal cancer do not contribute to increased rates of anastomotic leak. Proximal fecal diversion creates additional potential morbidity, higher rates of readmission, and need for a subsequent hospitalization and operation for reversal. Additionally, diverted patients have higher rates of anastomotic stricture and delayed recognition of chronic leaks. These downsides to diversion must be weighed with a patient's perceived ability to handle the physiologic stress and consequences of a severe leak if reoperation is required. When trying to determine which patients can handle a leak, the modified frailty index can help to objectively determine a patient's risk for increased rate of morbidity and failure to rescue in the event of a leak. While proximal diversion is still warranted in many cases, we find that certain clinical scenarios often lead to overuse of proximal diversion. The old surgical adage "If you are considering diverting, you should probably do it" should be tempered by an understanding of the risk and benefits of diversion.
PubMed: 36619277
DOI: 10.1055/s-0042-1757559 -
The Urologic Clinics of North America May 2002Approximately 20% of hypospadiac urethras are located proximally, anywhere from the penoscrotal to the perineal region. Repair of proximal defects is still one of the... (Review)
Review
Approximately 20% of hypospadiac urethras are located proximally, anywhere from the penoscrotal to the perineal region. Repair of proximal defects is still one of the most challenging surgical procedures facing the hypospadiologist. Modifications of current techniques for the correction of proximal hypospadias as well as new innovative techniques continue to be proposed.
Topics: Humans; Hypospadias; Male; Penis; Postoperative Care; Preoperative Care; Risk Factors; Surgical Flaps; Suture Techniques; Urethra; Urologic Surgical Procedures, Male
PubMed: 12371223
DOI: 10.1016/s0094-0143(02)00025-3 -
Proceedings of the National Academy of... Apr 2023First-order optimization algorithms are widely used today. Two standard building blocks in these algorithms are proximal operators (proximals) and gradients. Although...
First-order optimization algorithms are widely used today. Two standard building blocks in these algorithms are proximal operators (proximals) and gradients. Although gradients can be computed for a wide array of functions, explicit proximal formulas are known for only limited classes of functions. We provide an algorithm, HJ-Prox, for accurately approximating such proximals. This is derived from a collection of relations between proximals, Moreau envelopes, Hamilton-Jacobi (HJ) equations, heat equations, and Monte Carlo sampling. In particular, HJ-Prox smoothly approximates the Moreau envelope and its gradient. The smoothness can be adjusted to act as a denoiser. Our approach applies even when functions are accessible only by (possibly noisy) black box samples. We show that HJ-Prox is effective numerically via several examples.
PubMed: 36989305
DOI: 10.1073/pnas.2220469120 -
The Journal of the American Academy of... Jul 2015Proper understanding and restoration of sagittal balance is critical in spinal deformity surgery, including conditions such as adolescent idiopathic scoliosis and... (Review)
Review
Proper understanding and restoration of sagittal balance is critical in spinal deformity surgery, including conditions such as adolescent idiopathic scoliosis and Scheuermann kyphosis. One potential complication following spinal reconstruction is proximal junctional kyphosis. The prevalence of proximal junctional kyphosis varies in the literature, and several patient- and surgery-related risk factors have been identified. To date, the development of proximal junctional kyphosis has not been shown to lead to a negative clinical outcome following spinal fusion for adolescent idiopathic scoliosis or Scheuermann kyphosis. Treatment options range from simple observation in asymptomatic cases to revision surgery with extension of the fusion proximally. Several techniques and technologies are emerging that seek to address and prevent proximal junctional kyphosis.
Topics: Adolescent; Humans; Kyphosis; Reoperation; Risk Factors; Scheuermann Disease; Scoliosis; Spinal Fusion; Treatment Outcome
PubMed: 26002936
DOI: 10.5435/JAAOS-D-14-00143 -
Journal of B.U.ON. : Official Journal... 2014A considerable change in the anatomical distribution of colorectal cancer (CRC) towards more proximal sites has been observed in Western countries within the last 6-7... (Review)
Review
A considerable change in the anatomical distribution of colorectal cancer (CRC) towards more proximal sites has been observed in Western countries within the last 6-7 decades. As a result, tumors located proximally to the splenic flexure are now accounting for 30-40% (or even more) of overall CRC cases. This proximal migration is not always representing a true increase of proximal cancer, arising from various combinations of changes in the rates of proximal and distal cancer (e.g. proximal increase with distal stability/reduction, or decline in both sites albeit higher distally etc) in different areas and periods. Principal potential causes include ageing in Western populations (since proximal cancers are more common among the aged), various potentially site-specific exposures (lifestyle and medical) and systematic screening. Their effect is reflected in the particular shift patterns; for instance, widespread screening in USA has led to an overall CRC decline, more evident distally (for technical, anatomical and morphological reasons). Segmental disparities in particular characteristics (age, gender, morphology) and responses to various exposures are etiologically associated (for the most part) with underlying genetic differences between proximal and distal tumors. From clinical aspect, proximal shift necessitates a more generalized use of colonoscopy in screening programs. Potential interventions in treatment (segmental patient stratification) and prevention (identification of particular site-specific exposures) require further investigation.
Topics: Age Factors; Colorectal Neoplasms; Early Detection of Cancer; Genetic Predisposition to Disease; Humans; Life Style; Neoplasm Staging; Sex Factors
PubMed: 25261642
DOI: No ID Found -
International Journal of Impotence... Jan 2020Proximal corporal deformities may account for failed inflatable penile prosthesis (IPP) surgery. No contemporary series has focused solely on describing the natural...
Proximal corporal deformities may account for failed inflatable penile prosthesis (IPP) surgery. No contemporary series has focused solely on describing the natural history and management of isolated proximal corporal deformities in patients after IPP surgery. The aim of the current report is to present the clinical courses and surgical management with outcomes of proximal corporal deformities in the context of prior IPP implantation surgery. We conducted a retrospective analysis of the Johns Hopkins Hospital institutional database of IPP surgeries from May 2006 to March 2017 consisted of 198 patients who had undergone IPP revisions. All cases involving surgical revisions associated with isolated proximal corporal deformities (proximally from the penoscrotal junction) were identified. Data retrieved included clinical characteristics, operative findings, and surgical outcomes. Main outcome measures are the ability to achieve successful sexual intercourse after IPP revision. The findings of proximal corporal deformities were manifest in fifteen patients who had undergone previous IPP surgery. Deformities consisted of corporal dilatation (15 patients) and corporal rupture (8 patients). Associated prosthesis defects were mechanical failure (2 patients), aneurysmal dilatation (5 patients), and device breakage (4 patients). Median IPP treatment duration was 14 years. Mean number of prior IPP surgeries were 4.2 times. All patients underwent reduction corporoplasty with IPP device replacements consisting of controlled expansion devices. Mean age at revision was 59.7 years. All patients reported successful sexual intercourse and satisfaction within 6 months' follow-up after surgical revision. Proximal corporal deformities arising after IPP surgery are associated with dysfunctional device operation and as well as device defects. Proper recognition of this problem allows the opportunity for surgical correction with a definitive reduction corporoplasty. Failure to recognize these abnormalities timely may predispose to unsuccessful revisions and complicate future definitive surgical repair.
Topics: Adult; Databases, Factual; Erectile Dysfunction; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Patient Satisfaction; Penile Implantation; Penile Prosthesis; Penis; Reoperation; Retrospective Studies
PubMed: 30705434
DOI: 10.1038/s41443-019-0119-x -
ACG Case Reports Journal Dec 2022Plastic biliary stents are commonly placed during endoscopic retrograde cholangiopancreatography for various indications, and stent-related complications are uncommon....
Plastic biliary stents are commonly placed during endoscopic retrograde cholangiopancreatography for various indications, and stent-related complications are uncommon. We describe a case in which a plastic biliary stent migrated proximally through the liver capsule and diaphragm after endoscopic retrograde cholangiopancreatography, leading to pericardial effusion and cardiac tamponade. It is important for clinicians managing patients with biliary stents to be aware of this significant adverse event.
PubMed: 36628372
DOI: 10.14309/crj.0000000000000924 -
Clinical Epidemiology 2019We conducted a systematic review and meta-analysis aimed at evaluating the differences of diagnostic performance of fecal occult blood tests (FOBTs) in detecting... (Review)
Review
OBJECTIVE
We conducted a systematic review and meta-analysis aimed at evaluating the differences of diagnostic performance of fecal occult blood tests (FOBTs) in detecting advanced colorectal neoplasms located in the proximal versus distal colorectum.
METHODS
PubMed, Embase, Cochrane Library, and Web of Science were searched for eligible articles published before August 17, 2018. Two independent reviewers conducted study assessment and data extraction. Diagnosis-related indicators of FOBT for detecting proximal and distal colorectal neoplasms were summarized, and further stratified by the type of FOBT (guaiac-based FOBT (gFOBT) and immunochemical FOBT (iFOBT)). Pooled sensitivities and specificities were calculated using a random effect model. Summary receiver operating characteristic curves were plotted and area under the curves were calculated.
RESULTS
Overall, 31 studies meeting the inclusion criteria were included in this review. For gFOBT, we found no site-specific difference (proximally vs distally located) of pooled sensitivities observed in the colorectal cancer (CRC), advanced adenomas, and advanced neoplasms groups. As for iFOBT, pooled sensitivities for detecting CRC located in the distal colon/rectum were comparable with that in the proximal colon (proximal vs distal, 0.67, 95% CI 0.62-0.72 vs 0.72, 95% CI 0.68-0.75), while higher pooled sensitivities for detecting advanced adenomas and advanced neoplasms located in the distal colon/rectum than for detecting those in the proximal colon were observed for iFOBT with the values of 0.24 (95% CI 0.22-0.25) vs 0.32 (95% CI 0.30-0.34) and 0.25 (95% CIĀ 0.23-0.28) vs 0.38 (95% CI 0.36-0.40), respectively. Summary receiver operating characteristic curve analyses showed similar patterns for both types of FOBT regarding the diagnostic accuracy for detecting colorectal neoplasms according to the anatomical sites of the colorectum.
CONCLUSION
iFOBT had higher sensitivity for detecting advanced adenomas and advanced neoplasia located in the distal colon/rectum than that for those in the proximal colon.
PubMed: 31695506
DOI: 10.2147/CLEP.S213677 -
The Journal of Bone and Joint Surgery.... Nov 1996An anatomical study was performed to define the course of the radial nerve in the posterior aspect of the arm, with particular reference to its relationship to operative...
An anatomical study was performed to define the course of the radial nerve in the posterior aspect of the arm, with particular reference to its relationship to operative exposures of the posterior aspect of the humeral diaphysis. In ten cadaveric specimens, the radial nerve was found to cross the posterior aspect of the humerus from an average of 20.7 +/- 1.2 centimeters proximal to the medial epicondyle to 14.2 +/- 0.6 centimeters proximal to the lateral epicondyle. As it crossed the posterior aspect of the humerus in each specimen, the nerve had several branches to the lateral head of the triceps; however, no branches were found innervating the medial head of the triceps in the posterior aspect of any of the specimens. At the lateral aspect of the humerus, the nerve trifurcated into a branch to the medial head of the triceps, the lower lateral brachial cutaneous nerve, and the continuation of the radial nerve into the distal part of the upper arm and the forearm. Three operative approaches were performed in each specimen. The posterior triceps-splitting approach exposed an average of 15.4 +/- 0.8 centimeters of the humerus from the lateral epicondyle to the point at which the radial nerve crossed the posterior aspect of the humerus. For the second approach, the radial nerve was mobilized proximally to allow an additional six centimeters of the humeral diaphysis to be visualized. The third approach (the modified posterior approach) involved the identification of the radial nerve distally as it crossed the lateral aspect of the humerus, followed by reflection of both the lateral and the medial heads of the triceps medially. This exposure permitted visualization of 26.2 +/- 0.4 centimeters of the humeral diaphysis from the lateral epicondyle proximally. The results after use of the modified posterior approach in seven patients were also reviewed.
Topics: Female; Fracture Fixation; Humans; Humeral Fractures; Humerus; Male; Radial Nerve
PubMed: 8934483
DOI: 10.2106/00004623-199611000-00008