Long-term Outcomes After Bladder-preserving Tri-modality Therapy for Patients with Muscle-invasive Bladder Cancer: An Updated Analysis of the Massachusetts General Hospital Experience

Background

Tri-modality therapy (TMT) is a recognized treatment strategy for selected patients with muscle-invasive bladder cancer (MIBC).

Online adaptive algorithm for optimal control of structures subjected to travelling loads

The problem of adaptive optimal semiactive control of a structure subjected to a moving load is studied. The control is realised by a change of damping of the structure's supports. The results presented in the previous works of the authors demonstrate that switched optimal controls can be very efficient at reducing the vibration levels of the structure. On the other hand, these controls exhibit a high sensitivity to changes of the speed of the travelling load. The aim of this paper is to develop an algorithm that enables real‐time adaptation of the optimal controls according to both the measured speed of the travelling load and the estimated state of the structure. The control objective is to provide smooth passage for the vehicles and reduce the material stresses on the carrying structures. The designed adaptive algorithm uses reference optimal controls computed for constant speeds and a set of functions describing the sensitivity of the system dynamics to the measured parameters. The convergence of the algorithm, as well as aspects of its implementation, is studied. The performance of the proposed method is validated by means of numerical simulations conducted for different travelling speed scenarios. In the assumed objective functional, the proposed adaptive controller can outperform the reference optimal solutions by over 50%. The practicality of the proposed method should attract the attention of practising engineers.     

Longitudinal assessment of renal size and function in extremely low birth weight children at 7 and 11 years of age

Background

There are a lack of studies describing a longitudinal association between preterm delivery and renal complications later in life. We assessed renal size and function in preterm infants born with extremely low birth weight (ELBW) during 4 years of follow-up, comparing these parameters to age-matched children born full term (term controls).

Methods

The results of selected renal laboratory tests [levels of cystatin C, creatinine, blood urea nitrogen (BUN)] and of renal ultrasound evaluations were compared between the ELBW group and the term control group at age 7 and 11 years.

Results

The study population consisted of 64 children born with ELBW (ELBW children) who had been recruited at birth and 36 children born at term (term children) who took part in both follow-up assessments. Renal ultrasound examination revealed a significantly smaller renal volume in the 7- and 11-year-old ELBW children compared to the term controls [right kidney volume: 50.8 vs. 61.2 ml/m², respectively, at 7 years (p <0.01) and 51.4 vs. 58.2 ml/m², respectively, at 11 years (p <0.01); left kidney volume: 51.4 vs. 60.3 ml/m², respectively, at 7 years (p <0.01) and 55.2 vs. 60.7 ml/m², respectively, at 11 years (p?=?0.02)]. Renal function in ELBW children was also affected. Serum cystatin C levels were significantly higher in ELBW children than in the controls at 7 years of age, and this difference remained statistically significant at 11 years of age [0.63 vs. 0.59 mg/l, respectively, at 7 years (p?=?0.02) and 0.72 vs. 0.61 mg/l, respectively, at 11 years (p?=?0.01)]. Six ELBW children also had elevated cystatin C levels (0.97–1.11 mg/l) at 11 years of age. Cystatin C levels were within normal range in the ELBW children at age 7 years and in term children in both follow-up studies. BUN levels were higher in ELBW children at the age of 11 years (4.49 vs. 4.15 mmol/l; p?=?0.028).

Conclusion

Continued follow-up of these patients will reveal whether the observed worsening in renal function will persist into adulthood.

     

Preassembled stentless valved-conduit for the replacement of the ascending aorta and aortic root

Here we report the early clinical results of a new preassembled stentless valved-conduit incorporating artificial sinuses of Valsalva (BioValsalva). This new composite conduit incorporates a stentless porcine aortic valve (Elan, Vascutek Terumo, UK) suspended within a triple-layered vascular conduit (Triplex, Vascutek Terumo, UK) constructed with sinuses of Valsalva. Between December 2006 and January 2008, 17 patients with the mean age of 65 years underwent aortic valve, root and ascending aorta replacement with the BioValsalva valved-conduit. There was no perioperative mortality. There were no myocardial infarctions, cardiac failure or cerebrovascular events. Mean cardiopulmonary bypass time was 156+/-56 min and ischemic time was 112+/-33 min. Eight patients required deep hypothermic circulatory arrest for additional distal ascending aorta replacement. Mean mediastinal drainage was 499+/-262 ml. Postoperative transthoracic echocardiography and CT-scans of the aorta in all patients before discharge demonstrated well-functioning prosthetic aortic valves with small residual mean gradients, no regurgitation, and the presence of sinuses of Valsalva. In conclusion, the novel prefabricated, composite stentless valved-conduit BioValsalva possesses excellent hemodynamic performance and can be implanted with low morbidity. In addition, the conduit material has good hemostatic properties which reduced bleeding, and is easy to implant with a variety of surgical techniques.     

Arterial Hypertension due to Perirenal and Subcapsular Hematoma Induced by Renal Percutaneous Biopsy

In this study we report three patients, in whom arterial hypertension was induced by compression of the kidney parenchyma due to perirenal or subcapsular hematoma following percutaneous blind renal biopsy with use of Vim-Silverman type needle.     

HSP70-hom gene polymorphism in allogeneic hematopoietic stem-cell transplant recipients correlates with the development of acute graft-versus-host disease

BACKGROUND: A number of genetic polymorphisms have been shown to be associated with the outcome after allogeneic hematopoietic stem-cell transplantation (HSCT). In the present study, HSP70-hom polymorphism (+2763 G/A) was analyzed in the patients and donors of allogeneic HSCT in relation to transplantation outcome, susceptibility for generation of severe toxic lesions, and acute (a) graft-versus-host disease (GVHD). METHODS: One hundred thirty-three recipients of allogeneic hematopoietic stem cells and 64 haploidentical and matched unrelated donors were investigated. All these individuals were typed for dimorphism within the HSP70-hom gene (+2763 G/A) with the use of amplification refractory mutation system technique. RESULTS.: Patients with the HSP-AA homozygous genotype presented more frequently with grade II to IV toxic lesions (12 of 14 vs. 61 of 105, P = 0.039) and aGVHD (12 of 16 vs. 56 of 114, P = 0.045). Conversely, DRB1*11 was associated with a lower risk of aGVHD manifestation (10 of 31 vs. 58 of 99, P = 0.009). These contrary associations of HSP-AA and DRB1*11 with the risk of aGVHD were confirmed using logistic regression modeling in multivariable analysis (HSP-AA, odds ratio [OR] = 3.833, P = 0.004; DRB1*11, OR = 0.224, P = 0.048). None of donor HSP genotypes or patient-donor incompatibility within HSP alleles was associated with susceptibility to toxic complications or aGVHD. CONCLUSIONS: Polymorphism of the HSP70-hom gene is associated with the development of posttransplant complications. Recipient HSP-AA homozygous genotype is a risk factor for aGVHD.     

Effects of ranolazine on recurrent cardiovascular events in patients with non-ST-elevation acute coronary syndromes: the MERLIN-TIMI 36 randomized trial

Context  Ranolazine is a novel antianginal agent that reduces ischemia in patients with chronic angina but has not been studied in patients with acute coronary syndromes (ACS). Objective  To determine the efficacy and safety of ranolazine during long-term treatment of patients with non–ST-elevation ACS. Design, Setting, and Patients  A randomized, double-blind, placebo-controlled, multinational clinical trial of 6560 patients within 48 hours of ischemic symptoms who were treated with ranolazine (initiated intravenously and followed by oral ranolazine extended-release 1000 mg twice daily, n = 3279) or matching placebo (n = 3281), and followed up for a median of 348 days in the Metabolic Efficiency With Ranolazine for Less Ischemia in Non–ST-Elevation Acute Coronary Syndromes (MERLIN)-TIMI 36 trial between October 8, 2004, and February 14, 2007. Main Outcome Measures  The primary efficacy end point was a composite of cardiovascular death, myocardial infarction (MI), or recurrent ischemia through the end of study. The major safety end points were death from any cause and symptomatic documented arrhythmia. Results  The primary end point occurred in 696 patients (21.8%) in the ranolazine group and 753 patients (23.5%) in the placebo group (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.83-1.02; P = .11). The major secondary end point (cardiovascular death, MI, or severe recurrent ischemia) occurred in 602 patients (18.7%) in the ranolazine group and 625 (19.2%) in the placebo group (HR, 0.96; 95% CI, 0.86-1.08; P = .50). Cardiovascular death or MI occurred in 338 patients (10.4%) allocated to ranolazine and 343 patients (10.5%) allocated to placebo (HR, 0.99; 95% CI, 0.85-1.15; P = .87). Recurrent ischemia was reduced in the ranolazine group (430 [13.9%]) compared with the placebo group (494 [16.1%]; HR, 0.87; 95% CI, 0.76-0.99; P = .03). QTc prolongation requiring a reduction in the dose of intravenous drug occurred in 31 patients (0.9%) receiving ranolazine compared with 10 patients (0.3%) receiving placebo. Symptomatic documented arrhythmias did not differ between the ranolazine (99 [3.0%]) and placebo (102 [3.1%]) groups (P = .84). No difference in total mortality was observed with ranolazine compared with placebo (172 vs 175; HR, 0.99; 95% CI, 0.80-1.22; P = .91). Conclusions  The addition of ranolazine to standard treatment for ACS was not effective in reducing major cardiovascular events. Ranolazine did not adversely affect the risk of all-cause death or symptomatic documented arrhythmia. Our findings provide support for the safety and efficacy of ranolazine as antianginal therapy. Trial Registration  clinicaltrials.gov Identifier: NCT00099788      

Middle ear schwannoma--case report

Schwannoma is one of the common benign middle ear space tumors. The tumors may present with facial nerve paresis or palsy, otologic symptoms and/or parotid mass middle ear schwannomas may originate from the nerves of the tympanic caviti or by extensions from outside the middle ear space. Schwannomas of the facial nerve can occur along any segment, but they frequently involve the geniculate ganglion and extend proximally or distally from there. MRI and CT imaging characteristics are similar to those of vestibular schwannomas. We present the clinical and radiologic features of a middle-space schwannoma originating from facial nerve. The patient underwent middle ear exploration and mastoidectomy. The tumor was of facial nerve origin and was separated from middle ear. The pathologic diagnosis was schwannoma.     

Oral health and bone mineral density in postmenopausal women

ObjectiveThe objective of the study was to assess dental and periodontal status in relation to bone mineral density (BMD), and to study cytological changes in oral epithelium.MethodsThirty-seven postmenopausal women aged 50–70 were given a dental examination and a BMD assessment.ResultsThere was a relationship between the femoral neck BMD and teeth state, a negative correlation between the lumbar BMD and the periodontal disease index (PDI) and between the radius BMD and the papillary bleeding index (PBI). PDI correlated positively with the number of superficial cells in the marginal gingiva smears. Correlation between PDI and parabasal cells and the number of teeth was negative.ConclusionsIn observed postmenopausal women, there is a negative association between bone mineral density and teeth state and periodontal indices. Oral epithelium revealed atrophic changes resulting in low keratinization. The study suggests an association between decreasing in bone mineral density, alveolar bone loss and the numbers of various cell types in epithelial smears.     

Possible mechanisms of hypopigmentation in lichen sclerosus

Lichen sclerosus (LS) shares with vitiligo a milky-white appearance. By biopsy, pathognomonic dermal sclerosis readily distinguishes LS from vitiligo and other causes of leukoderma. To determine what the mechanism of hypopigmentation is in LS, we examined samples from LS cases for alterations in melanin content (Fontana-Masson stain) and melanocyte number (HMB-45 [PMEL-17/gp100], Mel-5 [TRP-1], Mart-1 [Melan A]) and compared these findings with those in controls of normal skin, acute scars, vitiligo, and lichen planus (LP; a common inflammatory cause of hyperpigmentation). The degree and extent of melanization found in LS overlapped with that in acute scars showing predominantly hypomelanized keratinocytes, with that in LP containing regions with numerous melanophages, and with that in vitiligo exhibiting focal regions of keratinocytes devoid of melanin pigment. By hematoxylin-eosin staining and immunocytochemistry for Mel-5 and Mart-1, LS had a lower mean count of melanocytes than acute scars, LP, and normal skin per 200 basal keratinocytes. In addition, a few LS cases had a significant loss of melanocytes comparable to that of vitiligo. Surprisingly, Mart-1 identified rare melanocytes in 67% of vitiligo cases and a significantly larger pool of melanocytes in LS and controls other than those labeled by Mel-5. Furthermore, LP and evolving lesions of LS contained the highest Mart-1 counts. HMB-45-immunoreactive melanocytes were found in the majority of acute scars and in LP and late-stage LS lesions at significantly lower levels than Mel-5- and Mart-1- labeled melanocytes, but they were not found in vitiligo or normal skin. We propose that several mechanisms may play a role in the production of leucoderma in LS: 1) decreased melanin production; 2) block in transfer of melanosomes to keratinocytes; and 3) melanocyte loss. The latter finding may be the pathogenic connection (lichenoid dermatitis of LS triggering an autoimmune reaction to melanocytes) that underlies the documented association of LS with vitiligo.