Living-Donor Kidney Transplantation Performed in a Low-Volume Center by Visiting Surgeons From a High-Volume Center and Managed Clinically Solely by Nephrologists: 1-Year Outcomes.

BACKGROUND: Little is known about the outcome of living-donor kidney transplantation (LDKT) performed in low-volume centers lacking the services of full-time transplant surgeons. This retrospective cohort study assessed the outcome of LDKT performed in a low-volume center by visiting transplant surgeons from a high-volume center and managed perioperatively by transplant nephrologists. METHODS: We compared Japanese adult patients who had no donor-specific antibodies and underwent LDKT between 2006 and 2015 either in a low-volume (n = 31) or high-volume (n = 481) center. In the low-volume center, visiting transplant surgeons from the high-volume center conducted LDKT and transplant nephrologists managed the recipients peri- and postoperatively. The primary outcome was the composite of infection, cardiovascular disease, or cancer during 1-year follow-up. The outcomes of the low- and high-volume centers were compared using 1:2 propensity score matching. RESULTS: After matching, 9 of 29 patients in the low-volume center (31.0%) and 16 of 58 patients in the high-volume center (27.6%) experienced the primary composite outcome (risk ratio = 1.13; 95% confidence interval, 0.57-2.23). There were no significant differences between the 2 groups in graft function at 1 year, all-cause graft loss, biopsy-proven rejection, and urological complications. However, the median duration of post-LDKT hospitalization was significantly longer in the low-volume center than in the high-volume center (23 and 16 days, respectively). CONCLUSIONS: Among Japanese patients without preformed donor-specific antibodies, LDKT conducted at a low-volume center by visiting transplant surgeons from a high-volume center and managed clinically by transplant nephrologists was not associated with significantly higher risk of postoperative complications.

A Novel Orally Available Delta-5 Desaturase Inhibitor Prevents Atherosclerotic Lesions Accompanied by Changes in Fatty Acid Composition and Eicosanoid Production in ApoE Knockout Mice.

Delta-5 desaturase (D5D), encoded by fatty acid desaturase 1 (Fads1), is the rate-limiting enzyme for the conversion from dihomo-γ-linolenic acid (DGLA) to arachidonic acid (AA) in the ω-6 polyunsaturated fatty acid pathway. Several AA-derived eicosanoids (e.g., prostaglandins, thromboxanes, and leukotrienes) and DGLA-derived eicosanoids are reported to promote and/or prevent atherosclerosis progression through, at least in part, its proinflammatory or anti-inflammatory effects. To elucidate the effects of D5D inhibition by a D5D inhibitor on atherosclerosis, we generated a potent, orally available and selective D5D inhibitor, 2-(2,2,3,3,3-Pentafluoropropoxy)-3-[4-(2,2,2-trifluoroethoxy) phenyl]-5,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-4,6-dione, compound-326, and examined its effects on Western-diet fed ApoE knockout (KO) mice. Oral administration of compound-326 (3-10 mg/kg per day for 15 weeks) significantly inhibited the progression of atherosclerotic lesions in the aorta without affecting plasma total cholesterol and triglyceride levels. Compound-326 significantly decreased AA levels, while it increased DGLA levels in the liver and the blood accompanied by decreases in AA-derived eicosanoid production and increases in DGLA-derived eicosanoid production from the blood cells. We conclude that compound-326 prevents the progression of atherosclerosis in Western-diet fed ApoE KO mice by modulating a profile of eicosanoid production, suggesting that D5D inhibitors can be a novel remedy for preventing atherosclerosis and subsequent cardiovascular events. SIGNIFICANCE STATEMENT: This study shows a D5D-specific and orally available potent inhibitor provided the first evidence to support the concept that D5D inhibitors will be a novel remedy for preventing the progression of atherosclerosis.

Synthesis and biological evaluation of novel selective androgen receptor modulators (SARMs). Part II: Optimization of 4-(pyrrolidin-1-yl)benzonitrile derivatives.

We recently reported a class of novel tissue-selective androgen receptor modulators (SARMs), represented by a naphthalene derivative A. However, their pharmacokinetic (PK) profiles were poor due to low metabolic stability. To improve the PK profiles, we modified the hydroxypyrrolidine and benzonitrile substituents of 4-(pyrrolidin-1-yl)benzonitrile derivative B, which had a comparable potency as that of compound A. This optimization led us to further modifications, which improved metabolic stability while maintaining potent androgen agonistic activity. Among the synthesized compounds, (2S,3S)-2,3-dimethyl-3-hydroxylpyrrolidine derivative 1c exhibited a suitable PK profile and improved metabolic stability. Compound 1c demonstrated significant efficacy in levator ani muscle without increasing the weight of the prostate in an in vivo study. In addition, compound 1c showed agonistic activity in the CNS, which was detected using sexual behavior induction assay.

[Morbidly obese patient with a huge ovarian tumor who was intubated while awake using airway scope in lateral decubitus position].

A morbidly obese woman with a huge ovarian tumor was scheduled to undergo tumor resection under general anesthesia. Under slight sedation with midazolam and fentanyl, a tracheal tube was inserted smoothly using Pentax-AWS Airway Scope, and general anesthesia was thereafter maintained by sevoflurane. To avoid circulatory collapse and reexpansion pulmonary edema, the content of the huge ovarian tumor was aspirated through a small drainage tube to reduce volume and weight of the tumor. Then resection of the ovarian tumor and abdominal wall tissue was performed in supine position. Periooperative course was uneventful.

Monitored anesthesia care with dexmedetomidine of a patient with severe pulmonary arterial hypertension for inguinal hernioplasty.

The presence of severe pulmonary arterial hypertension (PAH) is a significant risk factor of major perioperative cardiovascular complications in patients undergoing even non-cardiac surgery under anesthetic management. The most important aspect of perioperative care of PAH patients is to avoid pulmonary hypertensive crisis, which can be induced by alveolar hypoxia, hypoxemia, hypercarbia, metabolic acidosis, airway manipulations, and activation of the sympathetic nervous system by noxious stimuli. We report a case of successful monitored anesthesia care supplemented by dexmedetomidine for inguinal hernioplasty of a patient with severe PAH secondary to congenital heart disease.