Efficacy and safety of total lymphoid irradiation in different chronic lung allograft dysfunction phenotypes

Total lymphoid irradiation (TLI) is an alternative treatment for chronic lung allograft dysfunction (CLAD). However, data regarding its efficacy and tolerance are scarce. This study included patients with CLAD treated with TLI at our center between 2011 and 2018. Clinical characteristics before and after TLI and related complications were analyzed. Forty patients with CLAD (twenty-nine bronchiolitis obliterans syndrome [BOS], nine restrictive allograft syndrome [RAS], and two mixed) were included. Significant attenuation of the forced expiratory volume in 1-sec (FEV₁) decline slope was observed in all phenotypes, in both the BOS and RAS. The median FEV₁ 12, 6, and 3 months pre-TLI were as follows: 1980 (IQR 1720-2560), 1665 (IQR 1300-2340) and 1300 (IQR 1040-1740) ml (p < .001), while the median FEV₁ at 3, 6, and 12 months post-TLI was 1110 (IQR 810–1440), 1130 (IQR 860–1470), and 1115 (IQR 865–1490) ml (p = .769). No dropouts due to radiation toxicity were observed. The mean survival according to the Karnofsky Performance Status Scale (KPS) >70 or ≤70 at baseline was 1837 (IQR 259–2522) versus 298 (IQR 128–554) days (p < .0001), respectively. In conclusion, TLI may stop FEV₁ decline in both BOS and RAS. Moreover, a good KPS score may be an important prognostic factor.     

Does epidural versus combined spinal-epidural analgesia prolong labor and increase the risk of instrumental and cesarean delivery in nulliparous women?

Study ObjectiveTo compare duration of labor, mode of delivery, and local anesthetic consumed in women who received labor analgesia with epidural or combined spinal-epidural technique.DesignRetrospective, observational study.SettingDelivery room of a university hospital.Patients788 nulliparous women in labor at term with cervical dilation between three and 5 cm.InterventionsIn Group E (epidural alone), parturients received an epidural solution of 8 mL (levobupivacaine 0.125% with fentanyl 5 μg/mL). In Group CSE (combined spinal-epidural), parturients received a spinal injection of levobupivacaine two mg with fentanyl 15 μg (total volume two mL). Then an epidural catheter was placed in all patients and connected to a patient-controlled analgesia pump (basal infusion rate of 8 mL/hr of 0.1% levobupivacaine and fentanyl two μg/mL, patient-controlled bolus dose of three mL, and lockout time of 30 min).MeasurementsLabor duration, mode of delivery (spontaneous vaginal vs. instrumental delivery vs. cesarean section), and local anesthetic consumed, were recorded.Main ResultsLabor analgesia was performed with an epidural technique in 322 patients (40.9%), and a combined spinal-epidural technique in 466 patients (59.1%), of whom 39 Group E women (12.1%) and 46 Group CSE women (9.9%) required cesarean section (P=ns). No differences in the mode of delivery were observed between the groups. Time from analgesia to delivery (Group E: 217 ± 111 min vs. Group CSE: 213 ± 115 min; P=ns), and epidural local anesthetic consumed (Group E: 35 ± 20 mL vs. Group CSE: 33 ± 20 mL; P=ns), were similar in both groups.ConclusionsNo significant differences were observed between epidural and combined spinal-epidural given for labor analgesia in nulliparous women in duration of labor, mode of delivery, or local anesthetic consumed.     

Channels, carriers, and pumps in the pathogenesis of sodium-sensitive hypertension

Sodium-sensitive hypertension is thought to be dependent on primary alterations in renal tubular sodium reabsorption. The major apical plasma membrane Na(+) transporters include the proximal tubular Na(+)-H(+) exchanger, the thick ascending limb Na(+)-K(+)-2Cl(-) cotransport system, the distal tubular Na(+)-Cl(-) cotransporter, and the collecting duct epithelial sodium channel (ENaC). This article explores the role of each transporter in the pathogenesis of hypertension. Although the contribution of the proximal tubule Na(+)-H(+) exchanger is not yet defined completely, more convincing data have been generated about the importance of the Na(+)-K(+)-2Cl(-). Indeed at least 2 forms of hypertension appear to be related to the up-regulation of the transporter: the so-called programmed hypertension induced by low-protein diet during pregnancy and the early phase of hypertension in the Milan strain of rats. With respect to the Na(+)-Cl(-) cotransporter this may be overactive caused by inactivating mutation of WNK4 as in the Gordon syndrome, although it is the main actor for the maintenance phase of the hypertension found in the Milan strain of rats. Finally, the contribution of the ENaC has been established clearly; indeed, in the Liddle syndrome the mutation of the ENaC gene leads to a longer retention of the channel on the cell surface of collecting duct principal cells, thus inducing stronger sodium reabsorption along this segment. All these examples clearly indicate that renal sodium transporters may be responsible for various types of sodium-sensitive hypertension.     

Seat-belt injuries in children involved in motor vehicle crashes.

BACKGROUND: The efficacy of seat belts in reducing deaths from motor vehicle crashes is well documented. A unique association of injuries has emerged in adults and children with the use of seat belts. The "seat-belt syndrome" refers to the spectrum of injuries associated with lap-belt restraints, particularly flexion-distraction injuries to the spine (Chance fractures). METHODS: We describe the injuries sustained by 8 children, including 2 sets of twins, in 3 different motor vehicle crashes. RESULTS: All children were rear seat passengers wearing lap or 3-point restraints. All had abdominal lap-belt ecchymosis and multiple abdominal injuries due to the common mechanism of seat-belt compression with hyperflexion and distraction during deceleration. Five of the children had lumbar spine fractures and 4 remained permanently paraplegic. CONCLUSIONS: These incidents illustrate the need for acute awareness of the complete spectrum of intra-abdominal and spinal injuries in restrained pediatric passengers in motor vehicle crashes and for rear seat restraints that include shoulder belts with the ability to adjust them to fit smaller passengers, including older children.     

Influence of observer experience and training on proficiency in coronary CT angiography interpretation

Purpose

To assess the influence of experience and training on the proficiency in coronary CT angiography (CCTA) interpretation of practitioners with different levels of experience.

Methods and materials

Nine radiologist and cardiologist observers with varying prior CCTA experience ranging from novice to expert independently analyzed two case series of 50 catheter-correlated CCTA studies for coronary artery stenosis (0%, ≤49%, 50–74%, 75–99%, or 100%). Results of the first case series were unblinded and presented along with catheter angiography results to each reader before proceeding to the second series. Diagnostic accuracy on a per-segment basis was compared for all readers and both case series, respectively.

Results

Correlation coefficients between CCTA and catheter angiography initially ranged between good (r = 0.87) and poor (r = 0.26), depending on reader experience, and significantly (p < 0.05) improved in the second case series (range: r = 0.42 to r = 0.91). Diagnostic accuracy was significantly (p < 0.05) higher for more experienced readers (range: 96.5–97.8%) as compared to less experienced observers (range: 90.7–93.6%). After completion of the second case series for less experienced readers sensitivity and PPV significantly (p < 0.05) improved (range: 62.7–67.8%/51.4–84.1%), but still remained significantly (p < 0.05) lower as compared to more experienced observers (range: 89.8–93.3%/80.6–93.3%).

Conclusion

The level of experience appears to be a strong determinant of proficiency in CCTA interpretation. Limited one-time training improves proficiency in novice readers, but not to clinically satisfactory levels.     

Urinary concentration and tissue messenger RNA expression of monocyte chemoattractant protein-1 as an indicator of the degree of hydronephrotic atrophy in partial ureteral obstruction

PURPOSE: To find a potential prognostic marker of the induction of hydronephrotic atrophy in congenital hydronephrosis we investigated whether the messenger (m)RNA expression and urinary concentration of monocyte chemoattractant protein-1 (MCP-1) correlated with the degree of partial ureteral obstruction, and subsequent hydronephrotic atrophy and interstitial fibrosis. MATERIALS AND METHODS: We created left partial ureteral obstruction in 96 juvenile Wistar rats and complete ureteral obstruction in 18, while 16 underwent sham operation. Depending on excretion of contrast medium into the renal pelvis after 3 days we defined 2 degrees of hydronephrosis. Renal mRNA expression of MCP-1, and renal pelvic and bladder urinary concentrations of MCP-1 were measured after 1, 2 and 3 weeks, and compared with the degree of hydronephrotic atrophy. RESULTS: Grade 1 partial ureteral obstruction resulted in mild histological changes. Grade 2 partial and complete obstruction resulted in significant hydronephrotic atrophy. MCP-1 mRNA expression in the kidney remained unchanged in grade 1 partial obstruction but was moderately increased in grade 2 partial obstruction and clearly over expressed in complete ureteral obstruction. The renal pelvic urinary concentration of MCP-1 was not higher in rats with grade 1 partial obstruction than in sham operated animals but it was significantly increased in those with grade 2 partial and complete obstruction. CONCLUSIONS: mRNA expression and the urinary concentration of MCP-1 correlate with the degree of obstruction and subsequent renal damage in hydronephrosis. They may serve as prognostic markers in children with congenital hydronephrosis.     

Natural history of morbid obesity without surgical intervention.

BACKGROUND: To study the mortality among morbidly obese patients qualifying for bariatric surgery. Mortality from bariatric surgery for morbid obesity has been widely reported; however, little is known about the mortality in morbidly obese patients who defer surgery. METHODS: Consecutive patients evaluated for bariatric surgery with an initial encounter between 1997 and 2004 were identified. The Social Security Death Index and office records were used to identify mortality through 2006. We conducted telephone interviews to determine whether the 305 patients who did not undergo bariatric surgery at our institution had undergone the surgery elsewhere. Using Cox proportional hazards models, we compared the mortality in patients undergoing surgery with that of those who did not. To evaluate bias resulting from missing data, we conducted analyses assuming that all patients with missing data had (1) undergone surgery and (2) not undergone surgery. RESULTS: A total of 908 patients underwent bariatric surgery (880 patients at our institution and 28 patients elsewhere). A total of 112 patients did not undergo surgery. Data regarding surgery on 165 patients could not be obtained. The mortality in those patients who did not undergo surgery was 14.3% compared with 2.9% for those who did undergo surgery. Adjusting for age, gender, and body mass index, patients who had undergone surgery had an 82% reduction in mortality (hazard ratio 0.18, 95% confidence interval 0.09-0.35, P <.0001). Sensitivity analysis, assuming that all patients with missing data received surgery resulted in an 85% mortality reduction (P <.001) and assuming that patients did not receive surgery resulted in a 50% mortality reduction (P = .04). CONCLUSIONS: Mortality among morbidly obese patients without surgery was 14.3% during the study period. Surgical intervention offered a 50%-85% mortality reduction benefit.     

Effects of estrogen deficiency and low bone mineral density on healthy knee cartilage in rabbits

The purpose of this study was to compare the effects of estrogen deficiency and bone mass loss on normal knee cartilage in mature rabbits. Bilateral ovariectomy (OVX) was performed in 13 rabbits, 6 of which also received systemic glucocorticoid for 4 weeks. Seven additional healthy rabbits were used as controls. Bone mineral density (BMD) was measured by dual X‐ray absorptiometry in lumbar spine, knee, and subchondral bone of the knee at baseline and 22 weeks after OVX. After sacrifice, the knees were dissected, macroscopy was assessed, and histological cartilage abnormalities were evaluated according to the Mankin score. Correlations of Mankin with BMD at different regions were also performed. When compared to baseline, differences in BMD were only found in spine and knee of the animals receiving glucocorticoids. All the animals subjected to OVX had a significantly higher Mankin score than controls. Mankin was upper in OVX animals receiving glucocorticoids, but differences were not significant. The Mankin score was inversely related with BMD in lumbar spine (r = ?0.67; p < 0.01). Although low bone mineral density contributes to the minor osteoarthritic alterations observed in our model, estrogen deficiency itself seems to act directly to induce the main pathogenic effects in healthy cartilage of the rabbit. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:812–818, 2010     

Early Effects of Abaloparatide on Bone Formation and Resorption Indices in Postmenopausal Women With Osteoporosis

Anabolic osteoporosis drugs improve bone mineral density by increasing bone formation. The objective of this study was to evaluate the early effects of abaloparatide on indices of bone formation and to assess the effect of abaloparatide on modeling-based formation (MBF), remodeling-based formation (RBF), and overflow MBF (oMBF) in transiliac bone biopsies. In this open-label, single-arm study, 23 postmenopausal women with osteoporosis were treated with 80 μg abaloparatide daily. Subjects received double fluorochrome labels before treatment and before biopsy collection at 3 months. Change in dynamic histomorphometry indices in four bone envelopes were assessed. Median mineralizing surface per unit of bone surface (MS/BS) increased to 24.7%, 48.7%, 21.4%, and 16.3% of total surface after 3 months of abaloparatide treatment, representing 5.5-, 5.2-, 2.8-, and 12.9-fold changes, on cancellous, endocortical, intracortical, and periosteal surfaces (p < .001 versus baseline for all). Mineral apposition rate (MAR) was significantly increased only on intracortical surfaces. Bone formation rate (BFR/BS) was significantly increased on all four bone envelopes. Significant increases versus baseline were observed in MBF on cancellous, endocortical, and periosteal surfaces, for oMBF on cancellous and endocortical surfaces, and for RBF on cancellous, endocortical, and intracortical surfaces. Overall, modeling-based formation (MBF + oMBF) accounted for 37% and 23% of the increase in bone-forming surface on the endocortical and cancellous surfaces, respectively. Changes from baseline in serum biomarkers of bone turnover at either month 1 or month 3 were generally good surrogates for changes in histomorphometric endpoints. In conclusion, treatment with abaloparatide for 3 months stimulated bone formation on cancellous, endocortical, intracortical, and periosteal envelopes in transiliac bone biopsies obtained from postmenopausal women with osteoporosis. These increases reflected stimulation of both remodeling- and modeling-based bone formation, further elucidating the mechanisms by which abaloparatide improves bone mass and lowers fracture risk. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).