Transplanting Kidneys from Deceased Donors With Severe Acute Kidney Injury

Our aim was to determine outcomes with transplanting kidneys from deceased donors with acute kidney injury, defined as a donor with terminal serum creatinine ≥2.0 mg/dL, or a donor requiring acute renal replacement therapy. We included all patients who received deceased donor kidney transplant from June 2004 to October 2013. There were 162 AKI donor transplant recipients (21% of deceased donor transplants): 139 in the standard criteria donor (SCD) and 23 in the expanded criteria donor (ECD) cohort. 71% of the AKI donors had stage 3 (severe AKI), based on acute kidney injury network (AKIN) staging. Protocol biopsies were done at 1, 4, and 12 months posttransplant. One and four month formalin‐fixed paraffin embedded (FFPE) biopsies from 48 patients (24 AKI donors, 24 non‐AKI) underwent global gene expression profiling using DNA microarrays (96 arrays). DGF was more common in the AKI group but eGFR, graft survival at 1 year and proportion with IF/TA>2 at 1 year were similar for the two groups. At 1 month, there were 898 differentially expressed genes in the AKI group (p‐value <0.005; FDR <10%), but by 4 months there were no differences. Transplanting selected kidneys from deceased donors with AKI is safe and has excellent outcomes.     

Kv7.2 regulates the function of peripheral sensory neurons

The Kv7 (KCNQ) family of voltage‐gated K⁺ channels regulates cellular excitability. The functional role of Kv7.2 has been hampered by the lack of a viable Kcnq2‐null animal model. In this study, we generated homozygous Kcnq2‐null sensory neurons using the Cre‐Lox system; in these mice, Kv7.2 expression is absent in the peripheral sensory neurons, whereas the expression of other molecular components of nodes (including Kv7.3), paranodes, and juxtaparanodes is not altered. The conditional Kcnq2‐null animals exhibit normal motor performance but have increased thermal hyperalgesia and mechanical allodynia. Whole‐cell patch recording technique demonstrates that Kcnq2‐null sensory neurons have increased excitability and reduced spike frequency adaptation. Taken together, our results suggest that the loss of Kv7.2 activity increases the excitability of primary sensory neurons. J. Comp. Neurol. 522:3262–3280, 2014. © 2014 Wiley Periodicals, Inc.     

Therapiezieländerung und Therapiebegrenzung in der Intensivmedizin

The task of physicians is to maintain life, to protect and re-establish health as well as to alleviate suffering and to accompany the dying until death, under consideration of the self-determination rights of patients. Increasingly more and differentiated options for this are becoming available in intensive care medicine. Within the framework of professional responsibility physicians must decide which of the available treatment options are indicated. This process of decision-making is determined by answering the following question: when and under which circumstances is induction or continuation of intensive care treatment justified? In addition to the indications, the advance directive of the patient is the deciding factor. Medical indications represent a scientifically based estimation that a therapeutic measure is suitable in order to achieve a defined therapy target with a given probability. The ascertainment of the patient directive is achieved in a graded process depending on the state of consciousness of the patient. The present article offers orientation assistance to physicians for these decisions which are an individual responsibility.     

IMI Pathologic Myopia

Pathologic myopia is a major cause of visual impairment worldwide. Pathologic myopia is distinctly different from high myopia. High myopia is a high degree of myopic refractive error, whereas pathologic myopia is defined by a presence of typical complications in the fundus (posterior staphyloma or myopic maculopathy equal to or more serious than diffuse choroidal atrophy). Pathologic myopia often occurs in eyes with high myopia, however its complications especially posterior staphyloma can also occur in eyes without high myopia.Owing to a recent advance in ocular imaging, an objective and accurate diagnosis of pathologic myopia has become possible. Especially, optical coherence tomography has revealed novel lesions like dome-shaped macula and myopic traction maculopathy. Wide-field optical coherence tomography has succeeded in visualizing the entire extent of large staphylomas. The effectiveness of new therapies for complications have been shown, such as anti-VEGF therapies for myopic macular neovascularization and vitreoretinal surgery for myopic traction maculopathy.Myopia, especially childhood myopia, has been increasing rapidly in the world. In parallel with an increase in myopia, the prevalence of high myopia has also been increasing. However, it remains unclear whether or not pathologic myopia will increase in parallel with an increase of myopia itself. In addition, it has remained unclear whether genes responsible for pathologic myopia are the same as those for myopia in general, or whether pathologic myopia is genetically different from other myopia.     

A switch from GnRH agonist to GnRH antagonist in castration-resistant prostate cancer patients leads to a low response rate on PSA

Purpose

At the time of castration resistance, it is recommended to realize hormonal manipulations before chemotherapy. We evaluated the impact of a switch from GnRH agonist to antagonist in patients with castration-resistant prostate cancer on PSA and testosterone levels at 3 months.

Methods

Retrospectively, 17 patients from 5 different centers undergoing androgen deprivation therapy and presenting rising PSA confirmed on 3 blood samples 2 weeks apart and despite a castrate testosterone level (<0.5 ng/ml) were reviewed. Antiandrogen withdrawal syndrome had been tested before the switch. Degarelix was administered as followed: 240 mg for the first injection and then 80 mg every month, subcutaneously. We evaluated the PSA and testosterone level variation 3 months after the switch. Patients who experienced a variation in PSA of less than 10% compared to the baseline or who had a more than 10% PSA decrease were defined as responders.

Results

Mean PSA level at the switch was 34.3 ± 50.3 ng/ml, with a mean testosterone level of 0.21 ± 0.13 ng/ml. Three months after the switch, mean PSA level was 59.9 ± 81.6 ng/ml (P = 0.061), with a mean testosterone level of 0.19 ± 0.08 ng/ml (P = 0.086). At 3 months, 4 patients (23%) responded to therapy. Thirteen patients (77%) experienced a rise in PSA of more than 10% compared to baseline; 41% of patients decreased their testosterone level. The limitations of this study are its retrospective nature and the limited number of patients.

Conclusion

Switch from an agonist to an antagonist of GnRH has a limited impact on PSA at 3 months in castration-resistant prostate cancer patients.     

External Validation of Extranodal Extension and Lymph Node Density as Predictors of Survival in Node-positive Bladder Cancer after Radical Cystectomy

Background

Prognostic factors in pathologic node-positive patients after radical cystectomy are debated. Extranodal extension (ENE) and lymph node density (LND) are strong predictors of survival. The aim of this study was to assess factors predictive of survival and to evaluate the prognostic significance of the tumor, node, metastasis staging system (TNM) nodal classification in a retrospective cohort of node-positive bladder cancers after radical cystectomy.

Methods

We retrospectively reviewed the data of 75 patients with node-positive bladder cancer after radical cystectomy. Node pathological examination was performed by two experienced uropathologists. Cox regression analysis was performed to identify factors predictive of progression.

Results

The median number of removed lymph node was 18 (range 3–49). The median number of positive lymph nodes was 3 (range 1–35). Overall progression-free and cancer-specific survival were 5 and 12 %. In multivariate analysis, ENE, LND with a 20 % cutoff, and adjuvant chemotherapy were independent predictors of progression-free survival (p = 0.007, 0.006, <0.0001). Neither the 2002 nor the 2009 TNM nodal classification was associated with recurrence.

Conclusions

ENE and LND are strong predictors of clinical outcome in patients with node-positive bladder cancer treated by cystectomy. The actual TNM classification could probably be improved using these criteria, allowing better prognostic classification of node-positive bladder cancer after radical cystectomy.