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Invasive aspergillosis is a serious complication of solid organ transplantation. An early diagnosis is hampered by the lack of reliable serum markers and, even if appropriately diagnosed and treated with current antifungal agents, has a high mortality rate. We report a case of invasive pulmonary and cerebral aspergillosis in a renal transplant patient treated with IFN-γ in conjunction with combination anti-fungal therapy for six weeks in whom complete resolution of the fungal infection was achieved. Renal function remained intact throughout the treatment period. Surveillance CT scans of the chest and head showed resolution of prior disease but revealed a new left upper lobe mass four months after completion of treatment with IFN-γ. Biopsy of the lesion was positive for primary lung adenocarcinoma, for which she underwent left upper lobe resection. The pathology report confirmed clear surgical margins and lymph nodes and no evidence of fungal hyphae. IFN-γ should be considered early in the management of invasive aspergillosis in renal transplant patients. To date, allograft rejection has not been encountered.

The current study aimed to elucidate the regulatory mechanisms of the circRNA hsa_circ_0139697 (circSTAG2(16-25)) in BCa and to consider the opportunity of using circSTAG2(16-25) isolated from BCa patient urine as a marker for disease development prediction. The selection of this circRNA was determined by the special role of its parental gene STAG2 in BCa biology. The circRNA hsa_circ_0139697 was chosen from 25 STAG2 circRNAs due to its differential expression in the urine of BCa patients and healthy volunteers. Higher levels of circSTAG2(16-25) were detected in urine samples obtained from patients with recurrent tumors. A higher expression of circSTAG2(16-25) was also detected in more tumorigenic BCa cell lines. The overexpression of circSTAG2(16-25) in BCa cells induced the elevation of proliferation, motility, and invasion. To study the mechanisms of circSTAG2(16-25) activity, we confirmed that circSTAG2(16-25) can bind miR-145-5p in vitro as was predicted by bioinformatic search. miR-145-5p was shown to suppress some genes that promoted BCa progression. One of these genes, TAGLN2, encodes the protein Transgelin 2, which plays a role in BCa cell motility and invasion. Therefore, the possible mechanism of action of circSTAG2(16-25) could be sponging the tumor suppressor miR-145-5p, which results in activation of TAGLN2. In addition, circSTAG2(16-25) might be considered as a potential biomarker for recurrence prediction.

Given that impurities may affect the quality and safety of drug products, impurity identification and profiling is an integral part of drug quality control and is particularly important for newly developed medications such as solriamfetol, which is used to treat excessive daytime sleepiness. Although the high-performance liquid chromatography analysis of commercial solriamfetol has revealed the presence of several impurities, their synthesis, structure elucidation, and chromatographic determination have not been reported yet. To bridge this gap, we herein identified, synthesized, and isolated eight process-related solriamfetol impurities, characterized them using spectroscopic and chromatographic techniques, and proposed plausible mechanisms of their formation. Moreover, we developed and validated a prompt impurity analysis method based on ultrahigh-performance liquid chromatography with UV detection, revealing that its selectivity, linearity, accuracy, precision, and quantitation limit meet the acceptance criteria of method validation stipulated by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use. Thus, the developed method was concluded to be suitable for the routine analysis of solriamfetol substances., Competing Interests: The authors declare that there are no conflicts of interest., (© 2023 The Authors.)

Aim: To investigate the mechanism(s) by which potential effects of multi-drug highly-active antiretroviral therapy contributes to lipodystrophy syndrome., Methods: Preadipocytes from healthy donors were assessed for proliferation and differentiation in the presence of nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs) individually and in combination. Effects on proliferation were assessed with a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay and effects on differentiation were assessed from glycerol-3-phosphate dehydrogenase (GP DH) activity and quantitation of Oil Red O staining for intracellular lipid. Data were analyzed with a randomized block ANOVA with post-hoc Fisher's Least Significant Difference test., Results: Preadipocyte proliferation was inhibited by a combination of NNRTI + NRTI (14% at 48 h, P < 0.001) and PI + NRTI (19% at 48 h, P < 0.001) with additional suppression when ritonavir (RTV) was added (26% at 48 h). The drug combination of atazanavir (ATV) + RTV + emtricitabine (FTC) + tenofovir (TDF) had the greatest inhibitory effect on proliferation at 48 h. Preadipocyte differentiation was most significantly reduced by the efavirenz + FTC + TDF assessed either by GPDH activity (64%) or lipid accumulation (39%), P < 0.001. Combining NRTIs with a PI (ATV + FTC + TDF) significantly suppressed differentiation (GPDH activity reduced 29%, lipid accumulation reduced by 19%, P < 0.01). This effect was slightly greater when a boosting amount of RTV was added (ATV + FTC + TDF + RTV, P < 0.001)., Conclusion: Although combination antiretroviral therapy is clinically more efficacious than single drug regimens, it also has a much greater inhibitory effect on preadipocyte proliferation and differentiation., Competing Interests: Conflict-of-interest statement: The authors have no conflict of interest to disclose.

Background: Transplant renal artery stenosis (TRAS) is a common vascular complication after kidney transplantation and is associated with refractory hypertension, volume overload, and graft injury or loss. This article describes 5-year outcomes of endovascular intervention for TRAS with bare metal and drug eluting stents (DES)., Methods: We investigated, as a prospective cohort study, patient and graft outcomes after the targeted use of DES for vessel diameter less than 5 mm and bare metal stents (BMS) for vessel diameter greater than 5 mm as the primary management for TRAS., Results: From March 2008 to November 2014, 57 patients were stented for hemodynamically significant TRAS; 29 received DES, 26 received BMS, and 2 patients received both stent types. They were followed up for a mean of 35.1 ± 22.8 months; a subset of these patients who all received DES were followed up for 61.7 ± 17.5 months. Mean serum creatinine declined from 2.87 ± 1.5 mg/dL at the time of intervention to 1.98 ± 0.76 mg/dL ( P < 0.001) at one month follow-up and was 1.96 ±0.92 mg/dL ( P < 0.001) at 35.1 ± 22.8 months. Mean systolic blood pressure declined from 159.05 ± 19.68 mm Hg at time of intervention to 135.65 ± 15.10 mm Hg ( P < 0.001) at most recent visit. Clinically driven restenosis requiring repeat revascularization occurred in 15.7% of patients., Conclusions: Primary stenting with DES and BMS is both successful in the initial treatment of TRAS and also produced an immediate and long-term reduction in serum creatinine and systolic blood pressure., Competing Interests: The authors declare no conflicts of interest.

Whereas coronary aneurysms are commonly associated with Kawasaki disease, involvement of the renal vasculature is exceedingly rare. Genitourinary involvement in patients with Kawasaki disease is typically limited to sterile pyuria and proteinuria. In this case, a 13-year-old girl who presented with right flank pain and microhematuria was found to have an intraparenchymal hemorrhagic mass on computerized tomography scan. Renal arteriography confirmed the diagnosis of pseudoaneurysm in a lower pole segmental artery branch and complete occlusion was achieved with endovascular embolization., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Invasive aspergillosis is a serious complication of solid organ transplantation. An early diagnosis is hampered by the lack of reliable serum markers and, even if appropriately diagnosed and treated with current antifungal agents, has a high mortality rate. We report a case of invasive pulmonary and cerebral aspergillosis in a renal transplant patient treated with IFN-γ in conjunction with combination anti-fungal therapy for six weeks in whom complete resolution of the fungal infection was achieved. Renal function remained intact throughout the treatment period. Surveillance CT scans of the chest and head showed resolution of prior disease but revealed a new left upper lobe mass four months after completion of treatment with IFN-γ. Biopsy of the lesion was positive for primary lung adenocarcinoma, for which she underwent left upper lobe resection. The pathology report confirmed clear surgical margins and lymph nodes and no evidence of fungal hyphae. IFN-γ should be considered early in the management of invasive aspergillosis in renal transplant patients. To date, allograft rejection has not been encountered.

Transplant renal artery stenosis (TRAS) is a common occurrence following kidney transplantation with an incidence rate ranging from 6% to 23%. A single-center retrospective study was conducted to examine the use of drug-eluting stents (DES) in eligible patients with hemodynamically significant TRAS. Between March 2008 and January 2011, 12 patients were diagnosed with TRAS with reference vessel diameter measuring <5 mm and underwent endovascular intervention (EVI) with DES placement. TRAS was detected within the first year posttransplantation in a majority of these patients (83%) and manifested as hypertension (100%), allograft dysfunction (100%) and edema (58%). Procedural success rate was 100%. Patients were followed for a mean period of 16 ± 10 months. Blood pressure improved from a mean of 156/82 to 138/73 mmHg at the end of the follow-up period. In 11/12 patients, serum creatinine improved from 3.1 ± 1.3 mg/dL to 2.3 ± 0.5 mg/dL at the end of the follow-up period. TRAS of early onset is readily amenable to EVI with stent placement resulting in improvement in blood pressure control and allograft function., (©2011 The Authors Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Protease inhibitors (PIs) have been implicated in the development of HIV-associated lipodystrophy through a reduction in the differentiation of preadipocytes. While atazanavir (ATV) is associated with fewer clinical metabolic abnormalities in the short-term, the effects of long-term exposure are not known. ATV effects on preadipocyte replication or differentiation would indicate the potential for long-term problems. This study compared ritonavir (RTV) and ATV effects on preadipocyte replication and differentiation in human primary cultures. Preadipocytes from subcutaneous fat were studied in the presence of therapeutic concentrations of RTV and ATV for replication, differentiation, and adipokine secretion. The effects of the drugs on the expression of PPARgamma and related genes during differentiation were also assessed by real-time quantitative PCR. RTV induced a significant inhibition of preadipocyte proliferation, differentiation and adiponectin secretion. ATV at concentrations within the range of therapeutic levels did not affect differentiation or adiponectin secretion, but did have inhibitory effects on preadipocyte proliferation. Inhibition of differentiation by PIs was associated with decreased expression of PPARgamma, C/EBPalpha, and aP2 genes. In summary, although ATV at therapeutic levels has a smaller impact on adipogenesis, alterations in preadipocyte proliferation suggest the potential for adverse effects with long-term use.

Objectives: To examine the utility and potential limitations of microelectromechanical systems-based spectral-domain cystoscopic optical coherence tomography (COCT) so as to improve the diagnosis of early bladder cancer., Methods: An optical coherence tomography catheter was integrated into the single instrument channel of a 22F cystoscope to permit white-light-guided COCT over a large field of view (4.6 mm wide and 2.1 mm deep per scan at 8 frames/s) and 10-microm resolution. Intraoperative COCT diagnosis was performed in 56 patients, with a total of 110 lesions examined and compared with biopsied histology., Results: The overall sensitivity of COCT (94%) was significantly higher than cystoscopy (75%, P = .02) and voided cytology (59%, P = .005); the major enhancement over cystoscopy was for low-grade pTa-1 cancer and carcinoma in situ (P < .018). The overall specificity of COCT (81%) was comparable to voided cytology (88.9%, P = .49), but significantly higher than cystoscopy (62.5%, P = .02)., Conclusions: The microelectromechanical systems-based COCT, owing to its high resolution and detection sensitivity and large field of view, offers great potential for "optical biopsy" to enhance the diagnosis of nonpapillary bladder tumors and their recurrences and to guide bladder tumor resection.

Background and Purpose: Rhabdomyolysis is well known after traumatic crush injuries or ischemia involving muscles. Postoperatively, it most likely is secondary to surgical positioning and patient muscle mass. We report a case after laparoscopic live-donor nephrectomy., Case Report: A muscular 35-year-old man underwent elective left laparoscopic live-donor nephrectomy in a 70 degrees flank position with four ports. He was in the right-side lying position with hip flexion (flank position) for approximately 4 hours. A kidney bridge had been placed between the iliac crest and the rib cage. Postoperatively, the patient had light-pinkish urine and low urine output. There was marked induration of the buttocks and significant pedal and scrotal edema. With judicious use of alkalinization and diuretics, the patient did not require dialysis, and renal function returned to base level by postoperative day 20. The recipient of the kidney had a normal postoperative course., Conclusion: Rhabdomyolysis is a syndrome of muscle necrosis and release of intracellular components into the circulation. Acute renal failure secondary to myoglobinuria is a common complication. We currently use little flexion of the table during donor nephrectomy and bring the table to a neutral position immediately after kidney retrieval. Postoperatively, one needs a high index of suspicion for rhabdomyolysis to avoid or at least promptly recognize this rare but potentially serious condition after any operation lasting >or=4 hours.

1. The 1,480 patients awaiting cadaveric renal transplants at 14 Southern California transplant centers as of December 3, 1992, were compared with patients transplanted using a point system for one kidney and a hospital-based allocation for the second, or the current system allocating all locally procured kidneys by the point system with regard to several demographic parameters. 2. Of 1,472 waiting patients with sensitization data, 8.5% were broadly sensitized (> 80% PRA). Of the 737 kidneys allocated by the point system, 7% went to broadly sensitized patients, compared with 3% of 438 kidneys allocated by the hospitals (p < 0.001). 3. Of 1,470 waiting patients with information available, 23% were awaiting a repeat transplant. Under the point system, 18% of kidneys were used for repeat transplants compared with 9% of hospital-allocated kidneys (p < 0.001). 4. Of 1,434 waiting patients where the time waiting was available, 26% had waited 1-2 years, 12% 2-3 years, and 6% more than 3 years. Under the point system, patients waiting longer received significantly more kidneys than those recently added to the list: 35% had waited 1-2 years, 21% 2-3 years and 14% more than 3 years (p < 0.001). Kidneys allocated by the hospitals were transplanted to patients in approximately the same proportions as the waiting list: 29% to those waiting 1-2 years, 10% 2-3 years, and 3% more than 3 years. 5. Racial distribution of recipients was not significantly different under either allocation system from that of the waiting list. Whites comprised 39% of waiting patients, the same as the population of Los Angeles County.(ABSTRACT TRUNCATED AT 250 WORDS)