Role of second-line systemic treatment post-docetaxel in metastatic castrate resistant prostate cancer- current strategies and future directions

Treatment of metastatic castrate resistant prostate cancer (mCRPC) after progression on docetaxel chemotherapy is a challenging clinical scenario with limited availability of treatment options. Re-treatment with docetaxel, either as monotherapy or in combination with other cytotoxics or targeted agents has shown durable responses. However, most docetaxel re-treatment studies have been either retrospective or early phase non-randomised studies which have not formally assessed Quality of life or survival gain with re-treatment. Despite limited evidence for efficacy of mitoxantrone in the second-line, it continues to remain widely used, largely due to lack of available suitable alternatives. Cabazitaxel in combination with prednisolone is the only chemotherapy to have shown a significant survival benefit and receive approval by the U.S. Food and Drug Administration for patients with mCRPC previously treated with a docetaxel-based regimen. Abiraterone acetate has recently demonstrated a significant improvement in survival when compared to placebo in patients with docetaxel-treated mCRPC. This review aims to summarize the current evidence and discuss future strategies for treatment of mCRPC patients following failure of docetaxel chemotherapy.     

Bilateral proximal deep vein thrombosis and COVID‐19 in a patient with absence of inferior vena cava: A case report and review of literature

Bilateral proximal deep vein thrombosis (DVT) in the lower extremities of young patients should raise suspicion over pro‐thrombotic conditions and venous anatomical abnormalities, even in the presence of other precipitating factors, such as viral infection. The authors present a 33‐year‐old man with bilateral DVT and absence of inferior vena cava (AIVC), who also had concurrent COVID‐19, and discuss the management of this patient.     

Aggregation induced emission based fluorenes as dual-channel fluorescent probes for rapid detection of cyanide: applications of smartphones and logic gates

Rational modification of molecular structure by incorporating electron donating groups can play a potential role for designing aggregation induced emission (AIE) active fluorescent probes. Based on this principle, fluorescent probes (1a–c) were synthesized, and they displayed excellent aggregation induced emission (AIE) behavior in a H₂O/DMF (4 : 1, v/v) mixture due to restrictions in intramolecular charge transfer (ICT). As a comparison, probe 1d was synthesized by installing an electron withdrawing (–NO₂) group that surprisingly quenched the aggregation behaviour. Additionally, AIE active probes 1a–c displayed a highly sensitive dual channel (fluorometric and colorimetric) response towards rapid detection of CN⁻, which is an active toxic material. Probes 1a–c showed selectively enhanced fluorescence emission behavior towards CN⁻ with detection limits of 1.34 ppb, 1.38 ppb, and 1.54 ppb, respectively. The sensing mechanism involves Michael type adduct formation due to the nucleophilic addition reaction of cyanide with probes and was confirmed through ¹H NMR titration experiments. In contrast, probe 1d containing an electron withdrawing moiety showed insensitivity towards CN⁻. Therefore, this study provides the efficient strategy to induce AIE character in fluorescent probes and expands the mechanistic approach toward the sensing of toxic CN⁻.

Rational modification of molecular structure by incorporating electron donating groups can play a potential role for designing aggregation induced emission (AIE) active fluorescent probes.     

Prevalence and Factors Associated with Peripartum Hysterectomy among Iranian Pregnant Women: A Retrospective Study

BackgroundPeripartum hysterectomy (PPH) is one of the effective treatment modalities which is increasingly performed to save the life of pregnant women with uncontrollable severe postpartum hemorrhage. The aim of this study was to assess the prevalence and factors associated with PPH among Iranian pregnant women.MethodsIn a retrospective study, 33 pregnant women with PPH referred to Imam Khomeini Hospital in Sari, Mazandaran province, northern Iran were enrolled. Data were collected using census sampling from March 2017 to 2020. Patients'' sociodemographic and clinical characteristics were collected. Fisher''s exact test, Kruskal-Wallis, and Mann-Whitney tests were used to evaluate the study variables.ResultsThe prevalence of PPH among Iranian pregnant women was 2.81 per 1000 deliveries. The mean length of stay in the hospital and intensive care unit (ICU) was 6.15 (SD=2.91) and 3.17 (SD=1.50) days, respectively. Of the participants, 90.9% had a cesarean section, 51.6% had emergency PPH, 88.2% had emergency PPH in 24 hours after delivery, 9.1% had an induction, and 60.6% had PPH due to placental abnormalities. The mean duration of PPH procedure was 2.51 (SD=1.14) hours. The most common post-operative complication in participants was fever. Participants with older gestational age had more elective PPH (P=0.029). The length of ICU stay was more in patients with total PPH procedure compared to the supracervical (P<0.017). The induction rate was higher in emergency PPH after vaginal delivery compared to cesarean section (P=0.005).ConclusionThis study showed a high prevalence of PPH among pregnant women. Also, there was a significant relationship between the PPH and length of ICU stay, especially after supracervical hysterectomy. The results of this study can help obstetrician-gynecologist to provide a better intervention for managing patients with postpartum hemorrhage requiring PPH.     

Dialysis Access Graft Thrombolysis: Randomized Study of Pulse-Spray Versus Continuous Urokinase Infusion

Purpose: To compare pulse-spray to continuous-infusion thrombolysis with high-dose urokinase in thrombosed dialysis access grafts. Methods: A prospective randomized controlled trial was performed. From August 1992 to September 1993, 30 thrombosed polytetrafluoroethylene (PTFE) grafts in 24 patients were included, 15 grafts in each group. The success of thrombolysis, mean time to thrombolysis, mean urokinase dose, and 60-day patency rate were evaluated. Results: In the pulse-spray group, the mean time to thrombolysis was 72 min with a mean urokinase dose of 560,000 U. The 60-day patency rate was 71%. In the continuous-infusion group, the mean infusion time to thrombolysis was 55 min with a mean dose of 479,000 U. The 60-day patency rate was 73%. Conclusion: No statistically significant difference was found between the two techniques in the mean time to thrombolysis, the mean urokinase dose used, or the 60-day patency rate.     

Differential Bone Turnover in an Angulated Fracture Model in the Rat

We have developed a simple rat model of angulated tibial fracture which elicits substantial differences in bone formation and resorption within the same bone. In 35 rats the right mid-tibia was manually fractured and fixed with an intramedullary 17-gauge cannula needle. Twenty tibias were fixed in anterior angulation (27 ± 5°) and 15 in posterior angulation (31 ± 5°). Serial X-rays were taken over a 12-week period. All fractures healed completely within five weeks. In both groups, bone thickness was already significantly greater on the concave side than on the convex side at week 3 and remained so until the end of the experiment. The thickness on the convex side decreased dramatically within 3 to 5 weeks and gradually thereafter. For morphological analysis of bone mineralization, 3 rats from each group were given calcein and alizarin red injected at different time points up to 14 weeks. Maximum new bone formation was noted within the first 3 weeks. Over the ensuing weeks, new bone formation remained intense on the concave side, but it was virtually absent on the convex side. These results show that angulated fracture deformity reproducibly exhibits differential bone turnover, which can be exploited in research on local regulatory factors. To exemplify the utility of the model, an immunohistochemical study on two local markers was done. Callus tissue of five rats in the anterior angulation group at week 3 post-fracture was stained for the cytokine IL-1, a stimulator of bone resorption, and the neuropeptide CGRP, an inhibitor of resorption, showing clear differences in positive staining between the concave and convex sides. Our in-vivo model offers a means of analyzing morphologically and quantitatively the differential expression and action of factors involved in local bone turnover.     

Atorvastatin reduction of intravascular thrombosis, increase in cerebral microvascular patency and integrity, and enhancement of spatial learning in rats subjected to traumatic brain injury

OBJECT: Atorvastatin, a beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitor, has pleiotropic effects, such as promoting angiogenesis, increasing fibrinolysis, and reducing inflammatory responses, and has shown promise in enhancing recovery in animals with traumatic brain injury (TBI) and stroke. The authors tested the effect of atorvastatin on vascular changes after TBI. METHODS: Male Wistar rats subjected to controlled cortical impact injury were perfused at different time points with fluorescein isothiocyanate (FITC)--conjugated dextran 1 minute before being killed. Spatial memory function had been measured using a Morris Water Maze test at various points before and after TBI. The temporal profile of intravascular thrombosis and vascular changes was measured on brain tissue sections by using a microcomputer imaging device and a laser confocal microscopy. The study revealed the following results. 1) Vessels in the lesion boundary zone and hippocampal CA3 region showed a variety of damage, morphological alterations, reduced perfusion, and intraluminal microthrombin formation. 2) Atorvastatin enhanced FITC-dextran perfusion of vessels and reduced intravascular coagulation. 3) Atorvastatin promoted the restoration of spatial memory function. CONCLUSIONS. These results indicated that atorvastatin warrants investigation as a potential therapeutic drug for TBI.     

First 24-h SNAP-II score and highest PaCO2 predict the need for ECMO in congenital diaphragmatic hernia

Background/Purpose

Early clinical predictors for the use of ECMO in patients with congenital diaphragmatic hernia (CDH) are lacking. We sought to evaluate the first 24-h SNAP-II score and highest PaCO₂ as predictors of ECMO support and in-hospital mortality in neonates with CDH.

Methods

Retrospective review of 47 consecutive neonates with CDH admitted to our institution from January 2007 to December 2010 was performed. Covariates of ECMO use including SNAP-II score and highest PaCO₂ within the first 24 h of NICU admission were evaluated.

Results

Of the 47 infants in this study, 24 patients were supported with ECMO. The ECMO group had a higher incidence of pulmonary hypertension, higher PaCO₂, and higher 24-h SNAP-II scores. Only the SNAP-II score and not highest PaCO₂ predicted mortality following multivariate adjustment.

Conclusions

The first 24-h SNAP-II score and highest PaCO₂ may provide some prognostic value in identifying neonates who undergo ECMO support; however neither measure was independently associated with the use of therapy. Only the SNAP-II score was associated with in-hospital mortality following multivariate adjustment. Additional study is needed to validate these results in a larger data set.     

Inverted papilloma of ureter: a rare cause of hydronephrosis

A case of hydronephrosis with a rare underlying cause in a 35 years old male is described. He reported with pain in the left lumbar region with a past history of left ureterolithotomy. The ultrasound and IVU studies were suggestive of left hydronephroureter. CT Scan showed left hydronephroureter with narrowing at the lower end of left ureter. Ureterorenoscopy (URS) confirmed polypoidal lesions in the left lower ureter, completely obliterating the lumen and involving the whole circumferential wall of the lower ureter. The biopsy of the lesion revealed an inflammatory polyp. Accordingly open surgical intervention was planned. Excision of the lower third of left ureter with ureteric reimplantation was done with a Boari flap. The histopathology report of the lower third of ureter confirmed inverted papilloma of ureter. The patient made a smooth postoperative recovery.