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BACKGROUND: Guidelines suggest that active surveillance (AS) may be considered for select patients with favorable intermediate-risk (fIR) prostate cancer. OBJECTIVE: To compare the outcomes between fIR prostate cancer patients included by Gleason score (GS) or prostate-specific antigen (PSA). Most patients are classified with fIR disease due to either a 3 + 4 = 7 GS (fIR-GS) or a PSA level of 10-20 ng/ml (fIR-PSA). Previous research suggests that inclusion by GS 7 may be associated with worse outcomes. DESIGN SETTING AND PARTICIPANTS: We conducted a retrospective cohort study of US veterans diagnosed with fIR prostate cancer from 2001 to 2015. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We compared the incidence of metastatic disease, prostate cancer-specific mortality (PCSM), all-cause mortality (ACM), and receipt of definitive treatment between fIR-PSA and fIR-GS patients managed with AS. Outcomes were compared with those of a previously published cohort of patients with unfavorable intermediate-risk disease using cumulative incidence function and Grays test for statistical significance. RESULTS AND LIMITATIONS: The cohort included 663 men; 404 had fIR-GS (61%) and 249 fIR-PSA (39%). There was no evidence of difference in the incidence of metastatic disease (8.6% vs 5.8%, p = 0.77), receipt of definitive treatment (77.6% vs 81.5%, p = 0.43), PCSM (5.7% vs 2.5%, p = 0.274), and ACM (16.8% vs 19.1%, p = 0.14) between the fIR-PSA and fIR-GS groups at 10 yr. On multivariate regression, unfavorable intermediate-risk disease was associated with higher rates of metastatic disease, PCSM, and ACM. Limitations included varying surveillance protocols. CONCLUSIONS: There is no evidence of difference in oncological and survival outcomes between men with fIR-PSA and fIR-GS prostate cancer undergoing AS. Thus, presence of GS 7 disease alone should not exclude patients from consideration of AS. Shared decision-making should be utilized to optimize management for each patient. PATIENT SUMMARY: In this report, we compared the outcomes of men with favorable intermediate-risk prostate cancer in the Veterans Health Administration. We found no significant difference between survival and oncological outcomes.

Compare ICU outcomes and respiratory system mechanics in patients with and without acute kidney injury during invasive mechanical ventilation.DesignsRetrospective cohort study.SettingsICUs of the University of California, San Diego, from January 1, 2014, to November 30, 2016.PatientsFive groups of patients were compared based on the need for invasive mechanical ventilation, presence or absence of acute kidney injury per the Kidney Disease: Improving Global Outcomes criteria, and the temporal relationship between the development of acute kidney injury and initiation of invasive mechanical ventilation.InterventionsNone.Measurements and main resultsA total of 9,704 patients were included and 4,484 (46%) required invasive mechanical ventilation; 2,009 patients (45%) had acute kidney injury while being treated with invasive mechanical ventilation, and the mortality rate for these patients was 22.4% compared with 5% in those treated with invasive mechanical ventilation without acute kidney injury (p < 0.01). Adjusted hazard of mortality accounting for baseline disease severity was 1.58 (95% CI, 1.22-2.03; p < 0.001]. Patients with acute kidney injury during invasive mechanical ventilation had a significant increase in total ventilator days and length of ICU stay with the same comparison (both p < 0.01). Acute kidney injury during mechanical ventilation was also associated with significantly higher plateau pressures, lower respiratory system compliance, and higher driving pressures (all p < 0.01). These differences remained significant in patients with net negative cumulative fluid balance.ConclusionsAcute kidney injury during invasive mechanical ventilation is associated with increased ICU mortality, increased ventilator days, increased length of ICU stay, and impaired respiratory system mechanics. These results emphasize the need for investigations of ventilatory strategies in the setting of acute kidney injury, as well as mechanistic studies of crosstalk between the lung and kidney in the critically ill.

Increased plasma mitochondrial DNA concentrations are associated with poor outcomes in multiple critical illnesses, including COVID-19. However, current methods of cell-free mitochondrial DNA quantification in plasma are time-consuming and lack reproducibility. Here, we used next-generation sequencing to characterize the size and genome location of circulating mitochondrial DNA in critically ill subjects with COVID-19 to develop a facile and optimal method of quantification by droplet digital PCR. Sequencing revealed a large percentage of small mitochondrial DNA fragments in plasma with wide variability in coverage by genome location. We identified probes for the mitochondrial DNA genes, cytochrome B and NADH dehydrogenase 1, in regions of relatively high coverage that target small sequences potentially missed by other methods. Serial assessments of absolute mitochondrial DNA concentrations were then determined in plasma from 20 critically ill subjects with COVID-19 without a DNA isolation step. Mitochondrial DNA concentrations on the day of enrollment were increased significantly in patients with moderate or severe acute respiratory distress syndrome (ARDS) compared with those with no or mild ARDS. Comparisons of mitochondrial DNA concentrations over time between patients with no/mild ARDS who survived, patients with moderate/severe ARDS who survived, and nonsurvivors showed the highest concentrations in patients with more severe disease. Absolute mitochondrial DNA quantification by droplet digital PCR is time-efficient and reproducible; thus, we provide a valuable tool and rationale for future studies evaluating mitochondrial DNA as a real-time biomarker to guide clinical decision-making in critically ill subjects with COVID-19. [ABSTRACT FROM AUTHOR]

Keywords: giant prostatic calculi; moses technology; moses lithotripsy; dystrophic calcification; giant prostatic calculus; radiotherapy of prostate; #EndoUrology; #UroStone; #PCSM; #ProstateCancer; #uroonc EN giant prostatic calculi moses technology moses lithotripsy dystrophic calcification giant prostatic calculus radiotherapy of prostate #EndoUrology #UroStone #PCSM #ProstateCancer #uroonc 306 308 3 03/22/22 20220301 NES 220301 Abbreviations DC dystrophic calcification RT radiotherapy TURP transurethral resection of the prostate Case Presentation A 74-year-old man with a history of prostate cancer, nephrolithiasis, recurrent urinary retention presented to clinic with 2 years of pelvic discomfort and dysuria and a 1 week history of new onset haematuria and urethralgia. Giant prostatic calculi, moses technology, moses lithotripsy, dystrophic calcification, giant prostatic calculus, radiotherapy of prostate, #EndoUrology, #PCSM, #ProstateCancer, #uroonc, #UroStone. [Extracted from the article]

Rab proteins are conserved small GTPases that coordinate intracellular trafficking essential to cellular function and homeostasis. RAB-6.2 is a highly conserved C. elegans ortholog of human RAB6 proteins. RAB-6.2 is expressed in most tissues in C. elegans and is known to function in neurons and in the intestine tomediate retrograde trafficking. Here,we showthatRAB-6.2 is necessary for cuticle integrity and impermeability in C. elegans. RAB-6.2 functions in the epidermis to instruct skin integrity. Significantly, we show that expression of a mouse RAB6A cDNA can rescue defects in C. elegans epidermis caused by lack of RAB-6.2, suggesting functional conservation across phyla. We also show that the novel function of RAB-6.2 in C. elegans cuticle development is distinct from its previously described function in neurons. Exocyst mutants partially phenocopy rab-6.2-null animals, and rab-6.2-null animals phenocopy mutants that have defective surface glycosylation. These results suggest that RAB-6.2 may mediate the trafficking of one or many secreted glycosylated cuticle proteins directly, or might act indirectly by trafficking glycosylation enzymes to their correct intracellular localization. [ABSTRACT FROM AUTHOR]