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The presence of a cerebrospinal fluid (CSF) shunt was previously considered a contra-indication to laparoscopic surgery, however, case reports appeared that describe laparoscopic surgery proceeding with no adverse outcomes in such patients. check details The majority of these reports relate to laparoscopic cholecystectomy. Here we present what we believe to be only the second report of a patient undergoing laparoscopic bowel resection in the presence of a lumbo-peritoneal shunt. With this case we aim to add to the evidence that more major laparoscopic procedures can be performed safely in the presence of CSF shunts and with a brief review of the current evidence, have suggested appropriate monitoring and precautionary measures for approaching these procedures.We report a 71-year-old woman who presented with Posterior Reversible Encephalopathy Syndrome (PRES) in the setting of acute pancreatitis. On day 3 of her admission, she developed transient right-sided upper and lower limb weakness, reduced visual acuity and encephalopathy, initially regarded as an acute stroke. Brain MRI fluid-attenuated inversion recovery (FLAIR) T2 imaging performed the same day confirmed occipital and parietal hyperdensities consistent with PRES. Her blood pressure never exceeded 150/75 mm Hg throughout the course of the admission. Our case demonstrates PRES in the setting of acute pancreatitis with only a relatively moderate elevation in blood pressure. In order to prevent unnecessary intervention in the setting of presumed acute stroke, it is important to consider the potential differential diagnoses including PRES as rare masquerade of acute stroke or transient ischaemic attack.
Nephron hypertrophy and nephrosclerosis may be important determinants of CKD and mortality. However, studies of outcomes associated with these microstructural features have been limited to small tissue specimens from patients selected for either good kidney health or known kidney disease.
To determine whether microstructural features are predictive of progressive CKD and mortality outcomes, we studied patients who underwent a radical nephrectomy for a tumor. Large wedge sections of renal parenchyma distal to the tumor were stained and scanned into high-resolution images; we annotated the cortex and all glomeruli to calculate glomerular volume, cortex volume per glomerulus, and percentage of globally sclerotic glomeruli. Morphometric measurements also included percentages of artery luminal stenosis and interstitial fibrosis/tubular atrophy (IF/TA) of the cortex. At follow-up visits every 6-12 months, we determined which patients experienced progressive CKD (defined as dialysis, kidney transplantation, or aD, and IF/TA predicted noncancer mortality. Morphometric analysis of renal parenchyma can predict noncancer clinical events in patients long after their radical nephrectomy.
Synaptopodin (Synpo) is an actin-associated protein in podocytes and dendritic spines. Many functions in regulating the actin cytoskeleton
RhoA and other pathways have been ascribed to Synpo, yet no pathogenic mutations in the
gene have been discovered in patients. Naturally occurring Synpo isoforms are known (Synpo-short and -long), and a novel truncated version (Synpo-T) is upregulated in podocytes from
mutant mice. Synpo-T maintains some Synpo functions, which may prevent a podocyte phenotype from emerging in unchallenged mutant mice.
Novel mouse models were generated to further investigate the functions of Synpo. In one, CRISPR/Cas9 deleted most of the
gene, preventing production of any detectable Synpo protein. Two other mutant strains made truncated versions of the protein. Adriamycin injections were used to challenge the mice, and Synpo functions were investigated in primary cultured podocytes.
Mice that could not make detectable Synpo (
) did not develop any kidney abnormalities up to 12 months of age. However,
mice were more susceptible to Adriamycin nephropathy. In cultured primary podocytes from mutant mice, the absence of Synpo caused loss of stress fibers, increased the number and size of focal adhesions, and impaired cell migration. Furthermore, loss of Synpo led to decreased RhoA activity and increased Rac1 activation.
In contrast to previous findings, podocytes can function normally
in the absence of any Synpo isoform. Synpo plays a protective role in the context of podocyte injury through its involvement in actin reorganization and focal adhesion dynamics.
In contrast to previous findings, podocytes can function normally in vivo in the absence of any Synpo isoform. Synpo plays a protective role in the context of podocyte injury through its involvement in actin reorganization and focal adhesion dynamics.
The roles of asymptomatic hyperuricemia or uric acid (UA) crystals in CKD progression are unknown. Hypotheses to explain links between UA deposition and progression of CKD include that (
) asymptomatic hyperuricemia does not promote CKD progression unless UA crystallizes in the kidney; (
) UA crystal granulomas may form due to pre-existing CKD; and (
) proinflammatory granuloma-related M1-like macrophages may drive UA crystal-induced CKD progression.
MALDI-FTICR mass spectrometry, immunohistochemistry, 3D confocal microscopy, and flow cytometry were used to characterize a novel mouse model of hyperuricemia and chronic UA crystal nephropathy with granulomatous nephritis. Interventional studies probed the role of crystal-induced inflammation and macrophages in the pathology of progressive CKD.
Asymptomatic hyperuricemia alone did not cause CKD or drive the progression of aristolochic acid I-induced CKD. Only hyperuricemia with UA crystalluria due to urinary acidification caused tubular obstruction, infpathy and contribute to CKD progression because UA crystals trigger M1-like macrophage-related interstitial inflammation and fibrosis. Targeting proinflammatory macrophages, but not JAK/STAT signaling, can attenuate granulomatous interstitial nephritis.The use of animals for therapeutic benefit is well-established. For example, for individuals with a disability such as blindness, trained service dogs can enhance the ability to live independently and participate fully in society. An emotional support animal (ESA) is an untrained animal that is used to support a person disabled by an emotional or mental disorder. For an animal to qualify as an ESA, a mental health or medical professional needs to write a letter saying that the animal is needed for the mental health of the person with the disability. This article describes the legal framework for service animals and ESAs, as well as the differences between them. We summarize information about the Americans with Disabilities Act, the Fair Housing Act, the Air Carrier Access Act, and other laws governing an individual's right to be accompanied by a support animal. We also summarize the clinical research on ESAs and argue that, although there are few studies on the clinical effectiveness of ESAs, a broader body of research indicates that animals may have positive clinical effects on medical and mental illness. Finally, we suggest there is a need for further research and provider education on ESAs.Anticancer effects of aspirin, metformin, and statins against gastric cancer, one of the most common cancers in the world, have been reported. This retrospective cohort study aimed to investigate independent associations of aspirin, metformin, and statin use with gastric cancer incidence and mortality after adjustment for concomitant use of other drugs, using pooled cohort data extracted from the Korean National Health Insurance claim database. Follow-up started on January 1, 2004 and ended at the date of gastric cancer diagnosis, death, or December 31, 2013. Exposures to drugs were defined as cumulative duration of use for aspirin and cumulative defined daily dose for metformin and statin, and were entered as time-dependent variables in Cox analysis models to avoid immortal time bias. Use of aspirin for longer than 182.5 and 547.5 days during 2-year interval was associated with reduced risks of gastric cancer incidence and mortality, respectively. Patients with diabetes were at higher risk of gastric cancer ly.CT colonography for colorectal cancer screening has been proved to be effective and cost-saving. CT colonography uses minimally invasive evaluation of colorectum and has better patient acceptance, which appears to be a promising screening modality to improve low colorectal cancer screening rate. This study investigated the utilization patterns of CT colonography and factors associated with its use among U.S. adult population. This retrospective cross-sectional study analyzed the National Health Interview Survey 2015 and 2018. U.S. adults ages 45 or older without a history of colorectal cancer were included. Survey design-adjusted Wald F tests were used to compare the utilization of CT colonography during the study period. Multivariable logistic regression was used to identify the predictors of CT colonography among individual socioeconomic and health-related characteristics. The study sample included 34,768 individuals representing 129,430,319 U.S. adult population ages 45 or older. The overall utilization ofss then 1.4%) among US adults aged 45+ in 2018. More efforts are needed to implement strategies to increase CT colonography for effective CRC prevention.POLE mutations are a major cause of hypermutant cancers, yet questions remain regarding mechanisms of tumorigenesis, genotype-phenotype correlation, and therapeutic considerations. In this study, we establish mouse models harboring cancer-associated POLE mutations P286R and S459F, which cause rapid albeit distinct time to cancer initiation in vivo, independent of their exonuclease activity. Mouse and human correlates enabled novel stratification of POLE mutations into three groups based on clinical phenotype and mutagenicity. Cancers driven by these mutations displayed striking resemblance to the human ultrahypermutation and specific signatures. Furthermore, Pole-driven cancers exhibited a continuous and stochastic mutagenesis mechanism, resulting in intertumoral and intratumoral heterogeneity. Checkpoint blockade did not prevent Pole lymphomas, but rather likely promoted lymphomagenesis as observed in humans. These observations provide insights into the carcinogenesis of POLE-driven tumors and valuable information for genetic counseling, surveillance, and immunotherapy for patients. SIGNIFICANCE Two mouse models of polymerase exonuclease deficiency shed light on mechanisms of mutation accumulation and considerations for immunotherapy.See related commentary by Wisdom and Kirsch p. 5459.Breast cancer progresses in a multistep process from primary tumor growth and stroma invasion to metastasis. Nutrient-limiting environments promote chemotaxis with aggressive morphologies characteristic of invasion. It is unknown how coexisting cells differ in their response to nutrient limitations and how this impacts invasion of the metapopulation as a whole. In this study, we integrate mathematical modeling with microenvironmental perturbation data to investigate invasion in nutrient-limiting environments inhabited by one or two cancer cell subpopulations. Subpopulations were defined by their energy efficiency and chemotactic ability. Invasion distance traveled by a homogeneous population was estimated. For heterogeneous populations, results suggest that an imbalance between nutrient efficacy and chemotactic superiority accelerates invasion. Such imbalance will spatially segregate the two populations and only one type will dominate at the invasion front. Only if these two phenotypes are balanced, the two subpopulations compete for the same space, which decelerates invasion.
