This population-based registry was designed to provide robust and updated information on the characteristics and the epidemiology of chronic myeloid leukemia (CML). All cases of newly diagnosed ...Philadelphia positive, BCR-ABL1+ CML that occurred in a sample of 92.5 million adults living in 20 European countries, were registered over a median period of 39 months. 94.3% of the 2904 CML patients were diagnosed in chronic phase (CP). Median age was 56 years. 55.5% of patients had comorbidities, mainly cardiovascular (41.9%). High-risk patients were 24.7% by Sokal, 10.8% by EURO, and 11.8% by EUTOS risk scores. The raw incidence increased with age from 0.39/100,000/year in people 20-29 years old to 1.52 in those >70 years old, and showed a maximum of 1.39 in Italy and a minimum of 0.69 in Poland (all countries together: 0.99). The proportion of Sokal and Euro score high-risk patients seen in many countries indicates that trial patients were not a positive selection. Thus from a clinical point of view the results of most trials can be generalized to most countries. The incidences observed among European countries did not differ substantially. The estimated number of new CML cases per year in Europe is about 6370.
Osteoarthritis (OA) development is strongly associated with ageing, possibly due to age-related changes in transforming growth factor-β (TGF-β) signaling in cartilage. Recently, we showed that TGF-β ...suppresses interleukin (IL)-6 receptor (IL-6R) expression in chondrocytes. As IL-6 is involved in cartilage degeneration, we hypothesized that age-related loss of TGF-β signaling results in increased IL-6R expression and signaling in ageing cartilage.
Bovine articular cartilage was collected and immediately processed to study age-related changes in IL-6R expression using qPCR and IHC (age-range: 0.5–14 years). Moreover, cartilage from young and aged cows was stimulated with rhIL-6 and/or rhTGF-β1 to measure IL-6-induced p-STAT3 using Western blot. Expression of STAT3-responsive genes was analyzed using qPCR.
Expression of IL-6 receptor (bIL-6R) significantly increased in cartilage upon ageing (slope: 0.32, 95%CI: 0.20–0.45), while expression of glycoprotein 130 (bGP130) was unaffected. Cartilage stimulation with IL-6 showed increased induction of p-STAT3 upon ageing (slope: 0.14, 95%CI: 0.08–0.20). Furthermore, IL-6-mediated induction of STAT3-responsive genes like bSOCS3 and bMMP3 was increased in aged compared to young cartilage. Interestingly, the ability of TGF-β to suppress bIL6R expression in young cartilage was lost upon ageing (slope: 0.21, 95%CI: 0.13–0.30). Concurrently, an age-related loss in TGF-β-mediated suppression of IL-6-induced p-STAT3 and bSOCS3 expression was observed.
Ageing results in enhanced IL-6R expression and subsequent IL-6-induced p-STAT3 signaling in articular cartilage. This is likely caused by age-related loss of protective TGF-β signaling, resulting in loss of TGF-β-mediated IL-6R suppression. Because of the detrimental role of IL-6 in cartilage, this mechanism may be involved in age-related OA development.
Radiologic occult metastatic disease (ROMD) in patients with pancreatic ductal adenocarcinoma (PDAC) who undergo contemporary neoadjuvant chemotherapy (NAC) has not been well studied. This study ...sought to analyze the incidence, risk factors, and oncologic outcomes for patients who underwent the NAC approach for PDAC.
A retrospective review analyzed a prospectively maintained database of patients who had potentially resectable PDAC treated with NAC and were offered pancreatectomy at our institution from 2011 to 2022. Multivariable regression analysis was performed to assess risk factors associated with ROMD. Kaplan-Meier curves with log-rank analyses were generated to estimate time-to-event end points.
The study enrolled 366 patients. Upfront and borderline resectable anatomic staging comprised 80% of the cohort, whereas 20% had locally advanced disease. The most common NAC regimen was FOLFIRINOX (n = 274, 75%). For 55 patients (15%) who harbored ROMD, the most common site was liver-only metastases (n = 33, 60%). The independent risk factors for ROMD were increasing CA19-9 levels during NAC (odds ratio OR, 7.01; confidence interval CI, 1.97-24.96; p = 0.008), indeterminate liver lesions (OR, 2.19; CI, 1.09-4.39; p = 0.028), and enlarged para-aortic lymph nodes (OR, 6.87; CI, 2.07-22.74; p = 0.002) on preoperative cross-sectional imaging. Receipt of palliative chemotherapy (p < 0.001) and eventual formal pancreatectomy (p = 0.04) were associated with survival benefit in the log-rank analysis. The median overall survival (OS) of the patients with ROMD was nearly 15 months from the initial diagnosis, with radiologic evidence of metastases occurring after a median of 2 months.
Radiologic occult metastatic disease remains a clinical challenge associated with poor outcomes for patients who have PDAC treated with multi-agent NAC.
The opioid epidemic has reached a crisis level in America, and many institutions are implementing new guidelines to decrease opioid prescriptions. Although these may positively impact opioid ...addiction, its influence on patient satisfaction is inadequately described. The aim of the study was to evaluate the effect of standardized patient education and postoperative opioid regimens on patient satisfaction.
General surgery patients were counselled and given educational materials preoperatively regarding postoperative pain management. Inpatient discharge prescriptions were based on milligrams of oral narcotic required 24 hours before discharge. Outpatient procedure prescriptions were standardized. Postoperatively, patients received surveys regarding pain control and satisfaction.
Of the 198 patients studied, 96% agreed or strongly agreed that they were satisfied with their pain control. 92% agreed or strongly agreed they received enough medication; 7% disagreed, and 1% strongly disagreed. Educational materials were evaluated with 97% agreeing or strongly agreeing they received appropriate information concerning when and what to take. Fifty-five patients (28%) refused opioids or did not take any. Only 10 (5%) requested a refill.
Preoperative education and standardized postoperative narcotic prescribing can be highly effective while maintaining high patient satisfaction. Introduction across broad fields of surgery will allow uniformity for surgeons, trainees, nurses, pharmacists, and patients.
Surgical mesh and hernia repair have come under increasing scrutiny with large amounts of press, Internet, and social media reportage regarding ongoing mesh litigation, recalls, and patient ...testimonials. The aim of this study was to evaluate patient perceptions of mesh in hernia surgery.
A 16-question survey was given to patients presenting for hernia surgery at a tertiary hernia center by trained data analysts before surgeon interaction.
Two hundred and two patients were surveyed. Patients believed mesh caused complications (45.1%) and reported concerns about mesh (38.2%). Those who performed their own research, females, and patients with recurrent hernias were more likely to have concerns about mesh (P ≤ 0.03). Most patients (81.7%) thought they were at average risk or less for complications; patients with recurrent hernias (versus primary hernias) and incisional hernias (compared with inguinal or umbilical hernias) had more negative outlooks on complications (all P < .05). Recovery expectations varied, but the failed repair and incisional hernia groups were more likely to expect prolonged recovery (>3 months) (all P < .05). After surgeon-directed education and a mesh education handout, all but one patient agreed to and underwent a mesh repair as indicated.
Patients had concerns about mesh and were aware of mesh related complications. Patients performing their own research, as well as females and recurrent hernia patients, had worse perceptions of mesh. Recurrent and incisional hernia patients had greater concerns about complications, recurrence, and recovery. Preoperative education concerning mesh and mesh choice for each operation eased patient anxiety.
We determined whether an ovulatory estrus could be resynchronized in previously synchronized, AI nonpregnant cows without compromising pregnancy from the previous synchronized ovulation or to those ...inseminated at the resynchronized estrus. Ovulation was synchronized in 937 suckled beef cows at 6 locations using a CO-Synch + progesterone insert (controlled internal drug release; CIDR) protocol a 100-μg injection of GnRH at the time of progesterone insert, followed in 7 d by a 25-mg injection of PGF₂α at insert removal; at 60 h after PGF₂α, cows received a fixed-time AI (TAI) plus a second injection of GnRH. After initial TAI, the cows were assigned randomly to 1 of 4 treatments: 1) untreated (control; n = 237); 2) progesterone insert at 5 d after TAI and removed 14 d after TAI (CIDR5-14; n = 234); 3) progesterone insert placed at 14 d after TAI and removed 21 d after TAI (CIDR14-21; n = 232); or 4) progesterone insert at 5 d after TAI and removed 14 d after TAI and then a new CIDR inserted at 14 d and removed 21 d after TAI (CIDR5-21; n = 234). After TAI, cows were observed twice daily until 25 d after TAI for estrus and inseminated according to the AM-PM rule. Pregnancy was determined at 30 and 60 d after TAI to determine conception to the first and second AI. Pregnancy rates to TAI were similar for control (55%), CIDR5-14 (53%), CIDR14-21 (48%), and CIDR5-21 (53%). A greater (P < 0.05) proportion of nonpregnant cows was detected in estrus in the CIDR5-21 (76/110, 69%) and CIDR14-21 (77/120, 64%) treatments than in controls (44/106, 42%) and CIDR5-14 (39/109, 36%) cows. Although overall pregnancy rates after second AI service were similar, combined conception rates of treatments without a CIDR from d 14 to 21 68.7% (57/83); control and CIDR5-14 treatments were greater (P = 0.03) than those with a CIDR during that same interval 53.5% (82/153); CIDR5-21 and CIDR14-21 treatments. We conclude that placement of a progesterone insert 5 d after a TAI did not compromise or enhance pregnancy rates to TAI; however, conception rates of nonpregnant cows inseminated after a detected estrus were compromised when resynchronized with a CIDR from d 5 or 14 until 21 d after TAI.
Passive snubber networks are especially needed in fast switching power modules to prevent overvoltage from hard switching and to minimize electromagnetic interference 1. In a half-bridge circuit as ...shown in Fig. 1 (a) dissipative RC snubber networks are beneficial over single pulse capacitors as they do not generate a resonant pole in the impedance spectrum, which can be seen in Fig. 1 (b). As only a small capacitance (e.g. 4 nF) is needed to reduce the overvoltage (Fig. 1 (c)), a monolithically integrated RC snubber can be realized on a silicon chip and packaged directly on the power module substrate. An improved module performance was already demonstrated for chip snubbers with 200 V operating voltage 2. This work shows how the device design was enhanced for high manufacturability and reliable operations in a voltage range from 600 V to 900 V.
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