Negative Pressure Wound Therapy for Patients With Complicated Mucocutaneous Separation Following Ileal Conduit Urinary Diversion: A Case Series.

BACKGROUND: Mucocutaneous separation (MCS) is one of the early stomal complications of ileal conduit diversion after radical cystectomy. It can result in abdominal infection and sepsis, prolonging patient recovery. Negative pressure wound therapy (NPWT) has been widely used for abdominal wounds after orthopedic and burn surgery. This case series describes its use in complicated MCS and ostomy retraction after ileal conduit diversion. CASES: We describe a case series of 3 patients with moderate to severe MCS with and without infection after robot-assisted radical cystectomy with ileal conduit diversion. Our patients were treated with NPWT to avoid infection and create a satisfactory environment for healing MCS. After 2 to 4 weeks of NPWT, all 3 patients had normal micturition function with no additional peristomal wounds or complications. CONCLUSION: Negative pressure wound therapy may be used in the management of complicated MCS after ileal conduit diversion.

[Trans-Douglas Retzius' space-sparing robot-assisted simple prostatectomy for large-volume benign prostate hyperplasia].

OBJECTIVE: To report the safety and efficacy of trans-Douglas Retzius' space-sparing robot-assisted simple prostatectomy (RSS-RASP) in the treatment of large-volume BPH. METHODS: This retrospective study included 24 cases of large-volume (>80 ml) BPH treated by trans-Douglas RSS-RASP from August 2019 to June 2021. The patients ranged in age from 55 to 80 (mean 68.5) years, with an average body mass index of 25.1 (20.5－34.9) kg/m2 , median prostate volume of 132.4 (85.6－235.7) ml, and preoperative tPSA of 10.8 (0.5－37.9) ng/ml, IPSS of 25 (3－35) and quality of life (QOL) score of 5 (3－8). Before surgery, 12 of the patients received catheterization for urinary retention, 1 underwent cystostomy, 2 were complicated with hydronephrosis, 1 had stones and diverticulum in the bladder, and 14 were excluded from the cases of PCa by prostatic biopsy. The operation time, intraoperative blood loss, hemoglobin level on the first day after surgery, blood transfusion, and intra- and postoperative complications were recorded. The patients were followed up for 3 to 21 months postoperatively. Comparisons were made before and after operation in the IPSS, maximum urinary flow rate (Qmax), postvoid residual volume (PVR), QOL score, IIEF score and Male Sexual Health Questionnaire (MSHQ) score. RESULTS: Trans-Douglas RSS-RASP was successfully completed in all the 24 cases, with a mean operation time of 175 (100－285) min, intraoperative blood loss of 200 (50－800) ml, hemoglobin decrease of 25 (4－57) g/L on the first day after surgery, postoperative drainage tube indwelling of 3 (2－7) d, and urinary catheterization of 12 (4－18) d. Six (25%) of the patients received intraoperative blood transfusion, 1 underwent transurethral electrocoagulation hemostasis 1 month after surgery because of postoperative bleeding, and 1 received transurethral resection of the cicatrical adhesive tissue of the bladder neck 12 months after surgery. No other complications occurred postoperatively. The IPSS (3 ［1－7］), Qmax (19.6 ［9.9－32.1］ ml/s), PVR (0 ［0－34.9］ ml) and QOL score (2 ［0－3］) of the patients were significantly improved after surgery (P < 0.05), but no statistically significant differences were observed in the IIEF (20 ［19－24］) and MSHQ scores (14 ［13－14］) as compared with the baseline (P > 0.05). CONCLUSION: Trans-Douglas RSS-RASP is a safe and effective minimally invasive method for the treatment of large-volume (>80 ml) BPH, which can improve the urinary function of the patient after operation.

ortho-Alkylation of Pyridine N-Oxides with Alkynes by Photocatalysis: Pyridine N-Oxide as a Redox Auxiliary.

A photocatalyzed ortho-alkylation of pyridine N-oxide with ynamides and arylacetylenes has been developed, which yields a series of α-(2-pyridinyl) benzyl amides/ketones. Mechanistic studies, including electrochemical studies, radical-trapping experiments, and Stern-Volmer fluorescence quenching studies demonstrate that pyridine N-oxide serves as both a redox auxiliary and radical acceptor to achieve the mild photocatalytic single-electron oxidation of carbon-carbon triple bonds with the generation of a cationic vinyl radical intermediate.

[Combination of serum PSA assay, multi-parametric MRI and targeted prostate biopsy for prostate cancer screening in Nanjing].

OBJECTIVE: To investigate the exact prevalence of PCa among males in Nanjing and search for a mode of PCa screening suitable for the specific conditions. METHODS: From January to December 2018, we collected serum samples and clinical information from 6 903 men aged ≥50 years taking physical examination in 16 community health service centers in Nanjing. We proposed multi-parametric MRI (mpMRI) for those with serum PSA ≥4 µg/L, transperineal systematic biopsy and MRI/ultrasound fusion targeted prostate biopsy for those who scored ≥3 points on the Prostate Imaging-Reporting and Data System Version 2 (PI-RADS v2), transperineal systematic biopsy only for those with a PI-RADS v2 score of <3 and serum PSA ≥10 µg/L, and follow-up examinations every 6 months for those with a PI-RADS v2 score of <3 and serum PSA <4 µg/L. RESULTS: Among the 6 903 male subjects, 835 (12.1%) were found with serum PSA≥4 µg/L; 229 (77.4%) of the 296 men that received mpMRI scored ≥3 points on PI-RADS v2; and 79 (53.4%) of the 148 males that underwent prostate biopsy were diagnosed with PCa, with a total detection rate of 1.14% in all the subjects. Of the 77 patients with complete pathological data, 73 (94.8%) were found with clinically significant PCa, 30 (39.0%) with localized, 41 (53.2%) with locally advanced and 6 (7.8%) with metastatic malignancy, 6 (7.8%) in stage Ⅰ, 21 (27.3%) in stage Ⅱ, 34 (44.2%) in stage Ⅲ and 16 (20.8%) in stage Ⅳ. There were 47 (66.2%) high-risk, 18 (25.4%) moderate-risk and 6 (8.5%) low-risk cases among those with localized or locally advanced PCa. CONCLUSIONS: The prevalence of PCa in Nanjing deserves considerable attention, and PCa screening is highly necessary in the high-risk population, for which the combination of serum PSA assay, mpMRI and targeted prostate biopsy may be an ideal method.

Synthesis of Chiral Tetrasubstituted Azetidines from Donor-Acceptor Azetines via Asymmetric Copper(I)-Catalyzed Imido-Ylide [3+1]-Cycloaddition with Metallo-Enolcarbenes.

The all-cis stereoisomers of tetrasubstituted azetidine-2-carboxylic acids and derivatives that possess three chiral centers have been prepared in high yield and stereocontrol from silyl-protected Z-γ-substituted enoldiazoacetates and imido-sulfur ylides by asymmetric [3+1]-cycloaddition using chiral sabox copper(I) catalysis followed by Pd/C catalytic hydrogenation. Hydrogenation of the chiral p-methoxybenzyl azetine-2-carboxylates occurs with both hydrogen addition to the C=C bond and hydrogenolysis of the ester.

Cycloaddition reactions of enoldiazo compounds.

Enoldiazo esters and amides have proven to be versatile reagents for cycloaddition reactions that allow highly efficient construction of various carbocycles and heterocycles. Their versatility is exemplified by (1) [2+n]-cycloadditions (n = 3, 4) by the enol silyl ether units of enoldiazo compounds with retention of the diazo functionality to furnish α-cyclic-α-diazo compounds that are themselves subject to further transformations of the diazo functional group; (2) [3+n]-cycloadditions (n = 1-5) by metallo-enolcarbenes formed by catalytic dinitrogen extrusion from enoldiazo compounds; (3) [2+n]-cycloadditions (n = 3, 4) by donor-acceptor cyclopropenes generated in situ from enoldiazo compounds that produce cyclopropane-fused ring systems. The role of dirhodium(ii) and the emergence of copper(i) catalysts are described, as are the different outcomes of reactions initiated with these catalysts. This comprehensive review on cycloaddition reactions of enoldiazo compounds, with emphasis on methodology development, mechanistic insight, and catalyst-controlled chemodivergence, aims to provide inspiration for future discoveries in the field and to catalyze the application of enoldiazo reagents by the wider synthetic community.

Copper-Catalyzed Formal [4+2] Cycloaddition of Enoldiazoimides with Sulfur Ylides.

Enoldiazoimides, a new subclass of enoldiazo compounds, generate enol-substituted carbonyl ylides whose reactions with sulfur ylides enable an unprecedented formal [4+2] cycloaddition. The resulting multifunctionalized indolizidinones, which incorporate sulfur, are formed in good yields under mild reaction conditions. The uniqueness of this transformation stems from the role of the silyl-protected enol, since the corresponding acetyldiazoimide failed to provide any cross-products in metal-catalyzed reactions with sulfur ylides. This copper-catalyzed cycloaddition is initiated with the generation of enol-substituted carbonyl ylides and sulfur ylides from enoldiazoimides and sulfonium salts, respectively, and proceeds through stepwise six-membered ring formation, C-O and C-S bond cleavage, and silyl and acetyl group migration.

Comparison of 68Ga-PSMA-11 PET-CT with mpMRI for preoperative lymph node staging in patients with intermediate to high-risk prostate cancer.

BACKGROUND: To evaluate the diagnostic value of 68Ga-PSMA-11 PET-CT with multiparametric magnetic resonance imaging (mpMRI) for lymph node (LN) staging in patients with intermediate- to high-risk prostate cancer (PCa) undergoing radical prostatectomy (RP) with pelvic lymph node dissection (PLND). METHODS: We retrospectively identified 42 consecutive patients with intermediate- to high-risk PCa according to D'Amico and without concomitant cancer. Preoperative 68Ga-PSMA-11 PET-CT, pelvic mpMRI and subsequent robot assisted laparoscopic RP with PLND were performed in all patients. RESULTS: Among 42 patients assessed, the preoperative PSA value, Gleason score, pT stage and intraprostatic PCa volume of patients with LN metastases were all significantly higher than those without metastases (P = 0.029, 0.028, 0.004, respectively). The average maximum standardized uptake value (SUV) of 68Ga-PSMA-11 PET-CT positive PCa of patients with or without LN metastases were 13.10 (range 6.12-51.75) and 7.22 (range 5.4-11.2), respectively (P < 0.001). 68Ga-PSMA-11 PET-CT and pelvic mpMRI had the ability of succeed on preoperative definite accurate diagnosis and accurate localization of primary PCa in all 42 patients. Fifteen patients (35.71%) had a pN1 stage. 51 positive LN were found. Both 68Ga-PSMA-11 PET-CT and pelvic mpMRI displayed brillient patient-based and region-based sensitivity, specificity, negative predictive value and positive predictive value. There was no statistical difference for the detection of LNMs according to the diameter of the LNMs between 68Ga-PSMA-11 PET-CT and mpMRI in this study. CONCLUSIONS: Both 68Ga-PSMA-11 PET-CT and mpMRI performed great value for LN staging in patients with intermediate- to high-risk PCa undergoing RP with PLND. However, despite excellent performance of 68Ga-PSMA-11 PET-CT, it cannot replace mpMRI that remains excellent for lymph node staging.

Multicomponent reaction through cooperative trio catalysis incorporating enamine, Brønsted acid and metal Lewis acid catalysis: a concise route to access chromans.

An atom-economical multicomponent cascade reaction of salicylaldehydes, cyclohexanones and arylamines has been developed for the synthesis of three-ring fused chromans. This reaction was achieved through cooperative enamine-metal Lewis acid assisted Brønsted acid catalysis, furnishing the products in excellent yields with good diastereoselectivity.

Transperineal cryotherapy for unresectable muscle invasive bladder cancer: preliminary experience with 7 male patients.

BACKGROUND: Radical cystectomy (RC) with pelvic lymph node dissection (PLND) and urinary diversion (UD) is considered the standard treatment for muscle invasive bladder cancer (MIBC). In a part of patients, RC procedure is aborted due to unresectable disease, other followed treatment like systemic chemotherapy, radiotherapy or cryotherapy may be a better option. The aim of present study was to report the preliminary results of transperineal cryotherapy for unresectable muscle invasive bladder cancer. METHODS: From January 2011 to August 2013, 7 male patients with pT4b unresectable bladder cancer underwent bilateral ureterocutaneostomy. Two performed a pelvic lymph node dissection (PLND). Then primary transperineal cryosurgery for preserved bladder at the guidance of transrectal ultrasound (TRUS) was performed. All patients underwent a dual freeze-thaw cycle using third-generation cryotechnology with ultrathin 17-gauge cryoneedles. Computer tomography (CT) and/or magnetic resonance image (MRI)were performed at 3 month intervals after cryosurgery to determine whether progression or recurrence occurred. RESULTS: All cryosurgery was performed successfully, mean operation time was 76.43 ± 25.12 min (range 50-120 min), mean blood loss was 19.29 ± 15.92 ml (range 5-50 ml). Mean hospital stay was 3.86 ± 1.68 day (range 2-7 days). No operative related deaths occurred. Four patients dead due to the metastasis disease at the follow up time of 8, 15, 18 and 37 months, respectively. Six patients received postoperative therapy, of whom 5 patients were treated with combined chemoradiation, and the other one received chemotherapy alone. The progression free survival (PFS) of the 7 patients was 22.00 ± 14.61 months (range 3-40 months). The one, two and three year overall survival (OS) was 85.7%, 57.1% and 42.9%, respectively. CONCLUSION: Our results suggest that cryosurgery combination with chemoradiotherapy provide a safe and effective alternative method for unresectable pT4b bladder cancer. Longer follow-up is necessary to determine the sustained efficacy.

Catalytic Divergent [3+3]- and [3+2]-Cycloaddition by Discrimination Between Diazo Compounds.

Highly selective divergent cycloaddition reactions of enoldiazo compounds and α-diazocarboximides catalyzed by copper(I) or dirhodium(II) have been developed. With tetrakis(acetonitrile)copper(I) tetrafluoroborate as the catalyst epoxypyrrolo[1,2-a]azepine derivatives were prepared in good yields and excellent diastereoselectivities through the first reported [3+3]-cycloaddition of a carbonyl ylide. Use of Rh2 (pfb)4 or Rh2 (esp)2 directs the reactants to regioselective [3+2]-cycloaddition generating cyclopenta[2,3]pyrrolo[2,1-b]oxazoles with good yields and excellent diastereoselectivities.

Catalytic Asymmetric [3+1]-Cycloaddition Reaction of Ylides with Electrophilic Metallo-enolcarbene Intermediates.

The first asymmetric [3+1]-cycloaddition was successfully achieved by copper(I) triflate/double-sidearmed bisoxazoline complex catalyzed reactions of ß-triisopropylsilyl-substituted enoldiazo compounds with sulfur ylides. This methodology delivered a series of chiral cyclobutenes in good yields with high enantio- and diastereoselectivities (up to 99 % ee, and >20:1 d.r.). Additionally, the [3+1]-cycloaddition of catalytically generated metallo-enolcarbenes was successfully extended to reaction with a stable benzylidene dichlororuthenium complex.

Catalytic Asymmetric Synthesis of Cyclopentyl ß-Amino Esters by [3+2] Cycloaddition of Enecarbamates with Electrophilic Metalloenolcarbene Intermediates.

Chiral cyclopentyl ß-amino esters are formed catalytically by [3+2] cycloaddition reactions of enecarbamates with electrophilic metalloenolcarbenes in high yield with up to 98 % ee and excellent diastereocontrol. Use of ß-silyl-substituted enoldiazoacetates with a chiral dirhodium catalyst and trans-ß-arylvinylcarbamates are optimal for this transformation, which occurs with hydrogen-bond association between the vinylcarbamate and the intermediate metalloenolcarbene. Reductive conversion of the protected amino esters forms highly functionalized cyclopentyl ß-amino acids and 3-aminocyclopentanones.

Neutrophil Gelatinase Associated Lipocalin is an Independent Predictor of Poor Prognosis in Cases of Papillary Renal Cell Carcinoma.

PURPOSE: Neutrophil gelatinase associated lipocalin, also known as lipocalin-2, is a 25 kDa protein now considered the biochemical gold standard for the early diagnosis of acute kidney injury. Recently lipocalin-2 was suggested to have an important role in several human neoplasias. In this study we assess lipocalin-2 expression in 2 renal tumor types and analyze its association with clinicopathological parameters and prognosis. MATERIALS AND METHODS: The study group included 189 patients who underwent surgery for renal lesions between 2003 and 2013. Of these patients 105 had clear cell renal cell carcinoma and 84 had papillary renal cell carcinoma. The association of lipocalin-2 immunoexpression and clinicopathological characteristics was evaluated. Cox proportional hazard regression was performed to estimate the prognostic significance of potential confounders in predicting overall and disease-free survival. RESULTS: Lipocalin-2 expression in different histotypes of analyzed tumors was highly and significantly associated with papillary renal cell carcinoma (p <0.001). In papillary renal cell carcinoma high lipocalin-2 expression was associated with high Fuhrman grade (p <0.001), tumor size greater than 7 cm (p = 0.007), increased TNM stage (p <0.001) and lymph node metastasis (p = 0.009). On univariable and multivariable Cox survival analyses of papillary renal cell carcinoma, after a median followup of 49.1 months (range 7 to 136) lipocalin-2 expression was associated with reduced overall survival (HR 4.10, 95% CI 1.19-14.14, p = 0.026) and disease-free survival (HR 2.56, 95% CI 1.01-6.48, p = 0.047). CONCLUSIONS: Lipocalin-2 over expression may be a prognostic factor in decreased overall and disease-free survival in papillary renal cell carcinoma. The association of lipocalin-2 over expression and poor prognosis with papillary renal cell carcinoma may have potential diagnostic and therapeutic utility.

Trio catalysis merging enamine, brønsted Acid, and metal lewis Acid catalysis: asymmetric three-component aza-diels-alder reaction of substituted cinnamaldehydes, cyclic ketones, and arylamines.

A trio catalyst system, composed of arylamine, BINOL-derived phosphoric acid, and Y(OTf)3 , enables the combination of enamine catalysis with both hard metal Lewis acid catalysis and Brønsted acid catalysis for the first time. Using this catalyst system, a three-component aza-Diels-Alder reaction of substituted cinnamaldehyde, cyclic ketone, and arylamine is carried out with high chemo- and enantioselectivity, affording a series of optically active 1,4-dihydropyridine (DHP) derivatives are obtained in 91-99 % ee and 59-84 % yield. DHPs bearing a chiral quaternary carbon center are also obtained with good enantioselectivity and moderate yield (three examples). Preliminary mechanistic investigations have also been conducted.

Chiral Bimetallic Catalysts Derived from Chiral Metal Phosphates: Enantioselective Three-Component Asymmetric Aza-Diels-Alder Reactions of Cyclic Ketones.

A new type of chiral bimetallic catalyst is disclosed. These chiral bimetallic catalysts are easily formed through mixing a metal Lewis acid and a metal binaphthyl phosphate (MLA/M[P]3) in solution. (1)H and (31)P NMR spectroscopy, electron paramagnetic resonance (EPR) spectroscopy, matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry, and X-ray crystallographic analysis reveal a bimetallic structure of the Y(Yb)(III)/Y[P]3 complexes with bridging binaphthyl phosphate ligands. The Lewis acidity of these chiral bimetallic catalysts is readily tuned by changing either the metal Lewis acid or the chiral metal phosphate. Through cooperative metal Lewis acid-enamine catalysis, asymmetric three-component aza-Diels-Alder reactions of 5-, 6-, and 7-membered cyclic ketones, unsaturated ketoesters, and arylamines were successfully achieved to afford fused bicyclic dihydropyridines in high yields (up to 94%) with high enantioselectivity (up to 99% enantiomeric excess) and excellent chemoselectivity.

Calcific uremic arteriolopathy ameliorated by hyperbaric oxygen therapy in high-altitude area.

BACKGROUND: Calcific uremic arteriolopathy (CUA), previously called calciphylaxis, is a devastating complication of end-stage kidney disease (ESKD) with an annual incidence of 1-4% in dialysis patients and the mortality is as high as 80%. The rarity of the disease and the multifactorial nature of its causes have compromised good evidences that could determine the best therapy for the condition. For inhabitants in high-altitude area, the content of oxygen in the air is significantly lower than that in sea level area, which leads to the differences in the clinical manifestations and treatments to CUA. CASE PRESENTATION: We presented a patient with CUA on Tibetan Plateau successfully treated by hyperbaric oxygen (HBO). This 46-year-old uremic Tibetan peasant received hemodialysis for 10 years, and over the last six months, skin necrosis occurred progressively on the distal joint of the middle finger of his right hand and the distal knuckles became paled, hardened, and severely painful. Extensive calcification of the arteries of both hands was revealed and his serum phosphorus elevated and serum calcium decreased. After diagnosis of CUA, patient was treated with HBO therapy for successive three weeks with a session per day, on the basis of secondary infection prevention. Pain of the affected finger was quickly alleviated in one week and the lesions of the affected finger healed in two months. CONCLUSION: As the dialysis population in high-altitude area increasing rapidly in recent years, this management strategy of improving focal oxygen supply by HBO might act as a reference for the treatment of CUA patients in similar conditions.

Sc(OTf)3-catalyzed three-component cyclization of arylamines, ß,γ-unsaturated α-ketoesters, and 1,3-dicarbonyl compounds for the synthesis of highly substituted 1,4-dihydropyridines and tetrahydropyridines.

A Sc(OTf)3-catalyzed three-component cyclization reaction of arylamines, ß,γ-unsaturated α-ketoesters and 1,3-dicarbonyl compounds was developed to synthesize highly substituted 1,4-dihydropyridines and fused bicyclic tetrahydropyridines carrying a quaternary all-carbon center.

Photoredox-Catalyzed Divergent Radical Cascade Annulations of 1,6-Enynes via Pyridine N-Oxide-Promoted Vinyl Radical Generation.

The divergent organophotoredox-catalyzed radical cascade annulation reactions of 1,6-enynes were developed. A series of cyclopropane-fused hetero- and carbo-bicyclic, tricyclic, and spiro-tetracyclic compounds were facilely synthesized from a broad scope of 1,6-enynes and 2,6-lutidine N-oxide under mild and metal-free conditions with blue light-emitting diode light irradiation. The cascade annulation reaction occurs with the intermediacy of a ß-oxyvinyl radical, which is produced from photocatalytically generated pyridine N-oxy radical addition to the carbon-carbon triple bond.

Tumor-intrinsic RGS1 potentiates checkpoint blockade response via ATF3-IFNGR1 axis.

Background: Non-responsiveness is a major barrier in current cancer immune checkpoint blockade therapies, and the mechanism has not been elucidated yet. Therefore, it is necessary to discover the mechanism and biomarkers of tumor immunotherapeutic resistance. Methods: Bioinformatics analysis was performed based on CD8+ T cell infiltration in multiple tumor databases to screen out genes related to anti-tumor immunity. Associations between Regulator of G-protein signaling 1 (RGS1) and IFNγ-STAT1 signaling, and MHCI antigen presentation pathway were examined by RT-qPCR, western blotting, and flow cytometry. The modulatory mechanisms of RGS1 were investigated via CHIP-qPCR and dual-luciferase assay. The clinical and therapeutic implications of RGS1 were comprehensively investigated using tumor cell lines, mouse models, and clinical samples receiving immunotherapy. Results: RGS1 was identified as the highest gene positively correlated with immunogenicity among RGS family. Inhibition of RGS1 in neoplastic cells dampened anti-tumor immune response and elicited resistance to immunotherapy in both renal and lung murine subcutaneous tumors. Mechanistically, RGS1 enhanced the binding of activating transcription factor 3 (ATF3) to the promoter of interferon gamma receptor 1 (IFNGR1), activated STAT1 and the subsequent expression of IFNγ-inducible genes, especially CXCL9 and MHC class I (MHCI), thereby influenced CD8+ T cell infiltration and antigen presentation and processing. Clinically, lower expression level of RGS1 was associated with resistance of PD1 inhibition therapy and shortened progression-free survival among 21 NSCLC patients receiving immunotherapy. Conclusions: Together, these findings uncover a novel mechanism that elicits immunotherapy resistance and highlight the function of tumor-intrinsic RGS1, which brings new insights for future strategies to sensitize anti-PD1 immunotherapy.