Timing of radiotherapy (RT) after radical prostatectomy (RP): long-term outcomes in the RADICALS-RT trial (NCT00541047).

BACKGROUND: The optimal timing of radiotherapy (RT) after radical prostatectomy for prostate cancer has been uncertain. RADICALS-RT compared efficacy and safety of adjuvant RT versus an observation policy with salvage RT for prostate-specific antigen (PSA) failure. PATIENTS AND METHODS: RADICALS-RT was a randomised controlled trial enrolling patients with ≥1 risk factor (pT3/4, Gleason 7-10, positive margins, preoperative PSA≥10 ng/ml) for recurrence after radical prostatectomy. Patients were randomised 1:1 to adjuvant RT ('Adjuvant-RT') or an observation policy with salvage RT for PSA failure ('Salvage-RT') defined as PSA≥0.1 ng/ml or three consecutive rises. Stratification factors were Gleason score, margin status, planned RT schedule (52.5 Gy/20 fractions or 66 Gy/33 fractions) and treatment centre. The primary outcome measure was freedom-from-distant-metastasis (FFDM), designed with 80% power to detect an improvement from 90% with Salvage-RT (control) to 95% at 10 years with Adjuvant-RT. Secondary outcome measures were biochemical progression-free survival, freedom from non-protocol hormone therapy, safety and patient-reported outcomes. Standard survival analysis methods were used; hazard ratio (HR)<1 favours Adjuvant-RT. RESULTS: Between October 2007 and December 2016, 1396 participants from UK, Denmark, Canada and Ireland were randomised: 699 Salvage-RT, 697 Adjuvant-RT. Allocated groups were balanced with a median age of 65 years. Ninety-three percent (649/697) Adjuvant-RT reported RT within 6 months after randomisation; 39% (270/699) Salvage-RT reported RT during follow-up. Median follow-up was 7.8 years. With 80 distant metastasis events, 10-year FFDM was 93% for Adjuvant-RT and 90% for Salvage-RT: HR=0.68 [95% confidence interval (CI) 0.43-1.07, P=0.095]. Of 109 deaths, 17 were due to prostate cancer. Overall survival was not improved (HR=0.980, 95% CI 0.667-1.440, P=0.917). Adjuvant-RT reported worse urinary and faecal incontinence 1 year after randomisation (P=0.001); faecal incontinence remained significant after 10 years (P=0.017). CONCLUSION: Long-term results from RADICALS-RT confirm adjuvant RT after radical prostatectomy increases the risk of urinary and bowel morbidity, but does not meaningfully improve disease control. An observation policy with salvage RT for PSA failure should be the current standard after radical prostatectomy. TRIAL IDENTIFICATION: RADICALS, RADICALS-RT, ISRCTN40814031, NCT00541047.

Synthesis, crystal structure, Hirshfeld surface analysis, DFT, molecular docking and molecular dynamic simulation studies of (E)-2,6-bis(4-chlorophenyl)-3-methyl-4-(2-(2,4,6-trichlorophenyl)hydrazono)piperidine derivatives.

A novel drug to treat SARS-CoV-2 infections and hydroxyl chloroquine analogue, (E)-2,6-bis(4-chlorophenyl)-3-methyl-4-(2-(2,4,6-trichlorophenyl)hydrazono)piperidine (BCMTP) compound has been synthesized in one pot reaction. The novel compound BCMTP has been characterized by FT-IR, 1H-NMR, 13C-NMR and single-crystal X-ray diffraction patterns. Crystal packing is stabilized by C8-H8A•••Cl10i, C41-H41•••Cl1ii and N1-H1A•••Cl6iii intermolecular hydrogen bonds. From the geometrical parameters, it is observed that the piperidine ring adopts chair conformation. Hirshfeld surface analysis was carried out to quantify the interactions and an interaction energy analysis was done to study the interactions between pairs of molecules. The geometrical structure was optimized by density functional theory (DFT) method at B3LYP/6-31G (d, p) as the basic set. The smaller binding energy value provides the higher reactivity of BCMTP compound than hydroxyl chloroquine and was corrected by high electrophilic and low nucleophilic reactions. The stability and charge delocalization of the molecule were also considered by natural bond orbital (NBO) analysis. The HOMO-LUMO energies describe the charge transfer which takes place within the molecule. Molecular electrostatic potential has also been analysed. Molecular docking studies are implemented to analyse the binding energy of the BCMTP compound against standard drugs such as the crystal structure of ADP ribose phosphatase of NSP3 from SARS-CoV-2 in complex with MES and SARS-CoV-2 main protease with an unliganded active site (2019-nCoV, corona virus disease 2019, COVID-19) and found to be considered having better antiviral agents. Molecular dynamics simulation was performed for COVID-19 main protease (Mpro: 6WCF/6Y84) to understand the elements governing the inhibitory effect and the stability of interaction under dynamic conditions.

Projected and Observed Aridity and Climate Change in the East Coast of South India under RCP 4.5.

In the purview of global warming, the present study attempts to project changes in climate and quantify the changes in aridity of two coastal districts in south India under the RCP 4.5 trajectory. Projected climate change output generated by RegCM 4.4 model, pertaining to 14 grid points located within the study area, was analyzed and processed for this purpose. The meteorological parameters temperature and precipitations were used to create De Martonne Aridity Index, to assess the spatial distribution of aridity. The original index values ranged from 13.7 to 16.4 mm/°C, characterizing this area as a semidry climate. The outcome from the changed scenario analysis under RCP 4.5 showed that, during the end of the 21st century, the aridity may be increased more as the index values tend to reduce. The increasing trend in the drying phenomenon may be attributed to the rising of mean annual temperatures.

Combination treatment of low dose Anti-Thymocyte Globulin (ATG), Rituximab and high dose Sirolimus as induction agents in immune-conditioned recipients.

UNLABELLED: A prospective study was performed to evaluate low dose Anti-Thymocyte Globulin (ATG) and Rituximab along with high dose Sirolimus as induction agents for reducing the incidence of acute rejection in renal transplantation. 66 patients who were to undergo live renal transplantation were divided into the low risk Group I (GpI, n=41) and the high risk Group II (GpII, n=25) recipients. Induction therapy included single dose Rituximab (200 mg), ATG (2 mg/kg) and Sirolimus 12 mg/d administered minus 3 days pretransplant. All patients underwent splenic radiation and Double Filtration Plasmapheresis (DFPP). Post-operatively, all recipients received MMF, prednisolone 5-10 mg/d and Tacrolimus started when serum creatinine (Scr) fell below 2.5 mg/dl on the first Post Operative Day (POD). If creatinine still remained high second dose ATG and Sirolimus continued. Once serum creatinine fell below 1.5 mg/dl Tacrolimus initiated at 0.1 mg per kg per day dose stopping ATG. RESULTS: Acute rejection at 6 months for GpI was nil and for GpII it was 8%. Mean Scr on 1st POD was 1.8+/-0.6 mg/dl in GpI and 2.6+/-0.9 mg/dl in GpII. After 6 months the creatinine level in high risk was similar to that of low risk group (1.1+/-0.6 mg/dl in GpI and 1.2+/-0.8 mg/dl in GpII). No patient or graft loss was observed. Infections requiring hospitalization were observed in six patients and wound related complications requiring surgical intervention were observed in 4 of the 66 recipients. CONCLUSION: Low dose ATG with Rituximab and high dose Sirolimus can be used as induction agents in immune-conditioned recipients with better apparent results than using high dose induction ATG. This combinational regimen also helps in individualizing post-operative immunosuppressive drugs based upon the post-operative renal function.

Combined transurethral prostatectomy and inguinal hernia repair: a retrospective audit and literature review.

OBJECTIVE: To audit the results of combined transurethral resection of the prostate (TURP) and inguinal hernia repair, often carried out under the same anaesthetic (because bladder outlet obstruction from prostatic disease and inguinal hernia are both common conditions in elderly men), to avoid two separate operations. PATIENTS AND METHODS: The study included 85 patients who underwent primary inguinal hernia repair with TURP in the urology unit of Nottingham City hospital between 1989 and 1995, and who were recalled to a special clinic. The type of hernia and repair carried out were recorded and complications audited with specific reference to recurrence of hernia and wound infection. RESULTS: The 85 patients underwent 88 primary inguinal hernia repairs with TURP (three were bilateral). Maloney's darn repair was used on 55 and a Bassini repair on 33 occasions, respectively. Two patients developed mild wound infection after surgery, but only two patients (2%) had recurrence of hernia. CONCLUSIONS: The recurrence rate after primary inguinal herniorraphy with conventional methods of repair, performed with TURP, was comparable with published results of hernia repairs alone, before the introduction of Lichtenstein's mesh repair.