Citations

The clinical significance of valves within gonadal veins is controversial. In males, the absence of valves in the left testicular vein (compared to the right) has been cited as a potential mechanism for varicocele formation in the pampiniform plexus in the scrotum. In females, ovarian vein valve absence or incompetence may lead to pelvic congestion syndrome, a disputed explanation for pelvic, abdominal, and/or flank pain of unknown etiology. One study suggests that females have incompetent valves in dilated veins more frequently than males due to past pregnancies. Furthermore, inconsistencies exist in the reported incidence of gonadal vein valves, though pelvic insufficiency is more thoroughly documented and diagnosed in males than in females. This study assesses the presence, number, and location of gonadal vein valves in male and females. The right and left gonadal veins were evaluated in 13 embalmed cadavers (7 males, 6 females; mean age = 86.3 +/− 6.2 years). Twenty‐four veins were available for dissection; two veins were lost to dissection and therefore omitted. The veins were dissected from the ovary (females) or deep inguinal ring (males) to the point of drainage into the inferior vena cava (right gonadal vein) or left renal vein (left gonadal vein). The veins were incised along the entire length of this course, and the number and location of valves was noted and photographed. Anatomical variation and pathological dilation in the vasculature was also documented. A total of 8 valves were found among the 24 dissections. Valves were present in four of the six females (67%) compared to one out of seven males (14%). The valve in the male was located in the left gonadal vein; the bilateral distribution in females was more randomly patterned. The majority of the valves (87.5%) in females were located distally, adjacent to the ovary, while a single valve was located adjacent to the left renal vein confluence. No dilation was noted in any of the specimens. The male population in this study had a lower incidence of gonadal vein valves than in previous studies. However, the number of valves in female gonadal veins was considerably greater than in males. This finding has not been reported previously, perhaps due to the emphasis on male pelvic congestion as a risk for infertility versus attributing the condition in females to a psychosomatic etiology. The primary limitation of this research is the small sample size. Future work will explore the clinical implications of these preliminary findings in a patient population. Clinical correlation with patients who are suspected or known to suffer from pelvic congestion syndrome may shed further light on the role of gonadal vein valves in vein sufficiency and inform more effective treatment for this poorly understood condition in the female patient population.

OBJECTIVES: Multitarget stool DNA (MT-sDNA) testing has grown as a noninvasive screening modality for colorectal cancer (CRC), but real-world clinical data are limited in the post-FDA approval setting. The effect of previous colonoscopy on MT-sDNA performance is not known. We aimed to evaluate findings of colorectal neoplasia (CRN) at diagnostic colonoscopy in patients with positive MT-sDNA testing, stratified by patient exposure to previous colonoscopy. METHODS: We identified consecutive patients completing MT-sDNA testing over a 39-month period and reviewed the records of those with positive tests for neoplastic findings at diagnostic colonoscopy. MT-sDNA test positivity rate, adherence to diagnostic colonoscopy, and the positive predictive value (PPV) of MT-sDNA for any CRN and neoplastic subtypes were calculated. RESULTS: Of 16,469 MT-sDNA tests completed, testing returned positive in 2,326 (14.1%) patients. After exclusion of patients at increased risk for CRC, 1,801 patients remained, 1,558 (87%) of whom underwent diagnostic colonoscopy; 918 of 1,558 (59%) of these patients had undergone previous colonoscopy, whereas 640 (41%) had not. Any CRN was found in 1,046 of 1,558 patients (PPV = 67%). More neoplastic lesions were found in patients without previous colonoscopy (73%); however, the rates remained high among those who had undergone previous colonoscopy (63%, P < 0.0001). The large majority (79%) of patients had right-sided neoplasia. DISCUSSION: MT-sDNA has a high PPV for any CRN regardless of exposure to previous colonoscopy. Right-sided CRN was found at colonoscopy in most patients with positive MT-sDNA testing, representing a potential advantage over other currently available screening modalities for CRC.

AbstractContent used by Medical Physicists for fluoroscopy safety training to staff is deliverable via several formats, that is, online content or a live audience slide presentations. Here, we share one example of a kinesthetic (live, hands‐on simulation) educational program in use at our facility for some time (~10 years). In this example, the format and content specifically target methods of reducing physician operator exposures from scattered x rays. A kinesthetic format identifies and promotes the adoption of exposure‐reducing behaviors. Key kinesthetic elements of this type of training include: physician hands‐on measurements of radiation levels at locations specific to their standing positions (e.g., primary arterial access points) in the room using handheld exposure rate meters, measurement of exposure rate reduction to physicians provided by using personal protective equipment, that is, wearable aprons, hanging lead drapes, and pull‐down shields. Physician choice of procedure‐specific tableside selectable controls affecting exposure rate from optional fluoroscopy, Cine or digital subtraction angiography (DSA), along with comparative measured contribution to physician exposure is demonstrated. The inverse square exposure rate reduction to physicians when stepping back from the table during DSA is a key observation. Kinesthetic simulations in the rooms used by physicians have been found to provide the highest level of understanding giving rise to adoption of practices that are impactful for physicians. Specific training scripts are in place for physician sub‐specialization in interventional radiology, cardiology, neurosurgery, vascular surgery, and gastroenterology. This training is used for new physician staff while classroom presentations (whose content mimics in room training) are used with staff who have had previously had in room training.

Objective Activin A, an inflammatory mediator implicated in cellular senescence-induced adipose tissue dysfunction and profibrotic kidney injury, may become a new target for the treatment of diabetic kidney disease (DKD) and chronic kidney diseases. We tested the hypothesis that human DKD-related injury leads to upregulation of activin A in blood and urine and in a human kidney cell model. We further hypothesized that circulating activin A parallels kidney injury markers in DKD. Research design and methods In two adult diabetes cohorts and controls (Minnesota, USA; Galway, Ireland), the relationships between plasma (or urine) activin A, estimated glomerular filtration rate (eGFR) and DKD injury biomarkers were tested with logistic regression and correlation coefficients. Activin A, inflammatory, epithelial-mesenchymal-transition (EMT) and senescence markers were assayed in human kidney (HK-2) cells incubated in high glucose plus transforming growth factor-β1 or albumin. Results Plasma activin A levels were elevated in diabetes (n=206) compared with controls (n=76; 418.1 vs 259.3 pg/mL; p<0.001) and correlated inversely with eGFR (r s =−0.61; p<0.001; diabetes). After eGFR adjustment, only albuminuria (OR 1.56, 95% CI 1.16 to 2.09) and tumor necrosis factor receptor-1 (OR 6.40, 95% CI 1.08 to 38.00) associated with the highest activin tertile. Albuminuria also related to urinary activin (r s =0.65; p<0.001). Following in vitro HK-2 injury, activin, inflammatory, EMT genes and supernatant activin levels were increased. Conclusions Circulating activin A is increased in human DKD and correlates with reduced kidney function and kidney injury markers. DKD-injured human renal tubule cells develop a profibrotic and inflammatory phenotype with activin A upregulation. These findings underscore the role of inflammation and provide a basis for further exploration of activin A as a diagnostic marker and therapeutic target in DKD.

AbstractBackgroundClostridioides difficile infection (CDI) is associated with poor outcomes in inflammatory bowel disease (IBD) patients. Data are scarce on efficacy of fecal microbiota transplant (FMT) for recurrent CDI in IBD patients.MethodsWe reviewed health records of IBD patients (18 years of age or older) with recurrent CDI who underwent FMT. Outcomes of FMT for CDI were assessed on the basis of symptoms and stool test results.ResultsWe included 145 patients (75 women [51.7%]; median age, 46 years). Median IBD duration was 8 (range, 0–47) years, 36.6% had Crohn disease, 61.4% had ulcerative colitis, and 2.1% had indeterminate colitis. Median number of prior CDI episodes was 3 (range, 3–20), and 61.4% had received vancomycin taper. Diarrhea resolved after FMT in 48 patients (33.1%) without further testing. Ninety-five patients (65.5%) underwent CDI testing owing to post-FMT recurrent diarrhea; 29 (20.0%) had positive results. After FMT, 2 patients received empiric treatment of recurrent CDI without symptom resolution, suggesting IBD was the cause of symptoms. The overall cure rate of CDI after FMT was 80.0%, without CDI recurrence at median follow-up of 9.3 (range, 0.1–51) months. Forty-three patients (29.7%) had planned IBD therapy escalation after CDI resolution; none de-escalated or discontinued IBD therapy. Overall, 7.6% had worsening IBD symptoms after FMT that were treated as new IBD flares. No clinical predictors of FMT failure were identified.ConclusionsFew patients had new IBD flare after FMT. Fecal microbiota transplantation effectively treats recurrent CDI in IBD patients but has no apparent beneficial effect on the IBD course.

Purpose: To test the association between participant King-Devick Test (KDT) times and obstructive sleep apnea (OSA) severity and evaluate for improvement after continuous positive airway pressure (CPAP) treatment. Methods: Study dates January 30 to July 31, 2018. Patients were referred for initial evaluation of sleep disordered breathing concerns. OSA severities were defined by Apnea Hypopnea Index (AHI) results, with ≥15 considered at least moderate OSA. The KDT is an objective physical measure of brain function. We estimated correlation between KDT time and AHI and compared mean KDT time between patients with and without moderate OSA. For the OSA subgroup, we evaluated for potential improvement in KDT after CPAP. Results: We enrolled 60 participants, of whom 35 (58.3%) had OSA with an AHI ≥15. Initial analyses noted no significant KDT time differences between patients based on OSA severity. However, after excluding 3 participants who had baseline neurologic illness, adjusted analyses demonstrated that mean KDT time was significantly prolonged for patients with moderate or greater OSA (AHI ≥15) as compared to those with mild or no sleep apnea (AHI <15); 63.4 seconds (95% CI 58.9-67.8) versus 55.7 seconds (95% CI 50.2-61.1), P = .03. CPAP-treated subjects demonstrated significantly improved KDT test times; 63.5 seconds mean pretreatment versus 55.6 posttreatment; −6.6 seconds mean difference, 95%CI (−12.0, −1.13), P = .02. Conclusion: Neurologic abnormalities in patients with OSA are potentially demonstrable utilizing this objective physical measure. Significant improvement is achieved in patients after CPAP treatment.

Key Points Five-year follow-up of S1106 demonstrates similar efficacy, MRD negativity, and 5-year survival with RH or RB, but RH was more toxic than RB. RB showed excellent efficacy and survival and less toxicity compared with a cytarabine-based regimen in transplant-eligible MCL patients.

Abstract Introduction: The preferred post-remission therapy for older patients (pts) with AML remains uncertain. We compared outcomes for older AML pts in CR1 receiving HCT reported to the CIBMTR to older AML pts achieving CR1 on National Clinical Trials Network induction and non-HCT consolidation therapy (CT) trials. Methods: This study focused on pts 60-75 years of age treated between 2004 to 2013. CT pts (n=211) underwent induction and consolidation on Alliance for Clinical Trials in Oncology, ECOG-ACRIN or SWOG clinical trials for initial therapy for newly diagnosed AML; the CIBMTR provided data for HCT pts (n=431). CT patients received at least one cycle of CT on study and were excluded if HCT occurred at any time. Time to event started at CR1 and pts entered at CT or HCT, respectively, using left-truncation to account for differential entry times. Results: For the CT cohort, first consolidation included standard therapy (e.g., cytarabine or a hypomethylating agent) and additional study drug (e.g., bortezomib, dasatinib, sorafenib, and Zosuquidar, gemtuzumab) or tipifarnib alone. Among HCT pts, the donor was a HLA-matched sibling or unrelated donor (URD) in 66% and the others were partially HLA-matched/mismatched URD (10%) or cord blood (24%). HCT pts were younger and more frequently had high-risk AML (high WBC, secondary AML and unfavorable cytogenetics) (Table). The median time from CR1 to HCT and CT was 3.2 and 0.5 months, respectively. Allogeneic HCT showed worse overall survival (OS) (HR=1.52, p=0.02) prior to 9 months and better OS thereafter (HR= 0.53, p <0.0001) relative to CT (figure 1A). Treatment-related mortality (TRM) was worse after HCT in the first 9 months (HR=2.8, CI: 1.5 -5.2, p=.0009), while relapse was less frequent beyond 9 months after treatment (HR = 0.42, CI: 0.29 to 0.61, p<.0001). Despite higher early TRM, HCT recipients went on to manifest superior OS [5 year OS: HCT 29% (24-34%), CT 13.8% (9 -22%)] (Figure 1A). The benefit of HCT for survival after 9 months was more prominent in those with unfavorable cytogenetics (Figure 1B). Multivariate analysis for OS showed no statistically significant effect of age or performance status, while unfavorable cytogenetics were detrimental (HR=1.74, p<.0001). Conclusions. Allogeneic HCT led to heightened early risks from TRM, but resulted in superior long-term survival in older AML pts receiving HCT relative to CT by reducing relapse. Efforts to attenuate early TRM after allogeneic HCT may further improve HCT outcomes for older pts. Disclosures Ustun: novartis: Speakers Bureau. Attar:Agios: Employment, Equity Ownership. Larson:Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; BristolMyers Squibb: Consultancy, Research Funding; Ariad/Takeda: Consultancy, Research Funding. Roboz:Roche/Genentech: Consultancy; Eisai: Consultancy; Cellectis: Research Funding; Aphivena Therapeutics: Consultancy; Sandoz: Consultancy; Janssen Pharmaceuticals: Consultancy; Otsuka: Consultancy; Jazz Pharmaceuticals: Consultancy; Sandoz: Consultancy; AbbVie: Consultancy; Celltrion: Consultancy; Cellectis: Research Funding; Eisai: Consultancy; Astex Pharmaceuticals: Consultancy; Argenx: Consultancy; Pfizer: Consultancy; Celgene Corporation: Consultancy; Novartis: Consultancy; Jazz Pharmaceuticals: Consultancy; Bayer: Consultancy; Bayer: Consultancy; Roche/Genentech: Consultancy; Orsenix: Consultancy; Astex Pharmaceuticals: Consultancy; Celgene Corporation: Consultancy; Daiichi Sankyo: Consultancy; Pfizer: Consultancy; Janssen Pharmaceuticals: Consultancy; Otsuka: Consultancy; Orsenix: Consultancy; Daiichi Sankyo: Consultancy; Celltrion: Consultancy; Novartis: Consultancy; Aphivena Therapeutics: Consultancy; Argenx: Consultancy; AbbVie: Consultancy. Uy:GlycoMimetics: Consultancy; Curis: Consultancy. Stone:Fujifilm: Consultancy; Ono: Consultancy; Orsenix: Consultancy; Otsuka: Consultancy; Agios: Consultancy, Research Funding; AbbVie: Consultancy; Argenx: Other: Data and Safety Monitoring Board; Celgene: Consultancy, Other: Data and Safety Monitoring Board, Steering Committee; Arog: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Jazz: Consultancy; Astellas: Consultancy; Merck: Consultancy; Pfizer: Consultancy; Sumitomo: Consultancy; Amgen: Consultancy; Cornerstone: Consultancy. Foran:Agios: Research Funding; Xencor, Inc.: Research Funding. Weisdorf:Seattle Genetics: Consultancy; Equillium: Consultancy; FATE: Consultancy; SL Behring: Consultancy; Pharmacyclics: Consultancy.