Limited-Stage Small Cell Lung Cancer: Is Prophylactic Cranial Irradiation Necessary?

PurposeProphylactic cranial irradiation (PCI) reduces the incidence of brain metastases in patients with limited stage small cell lung cancer (LS-SCLC). However, PCI is associated with neurotoxicity. Previous studies have not consistently used pretreatment magnetic resonance imaging. Modern imaging improvements continue to enhance early metastasis detection, potentially decreasing the utility of PCI. We sought to determine whether PCI was associated with improved outcomes in LS-SCLC patients with modern imaging.Methods and MaterialsWe identified LS-SCLC patients with no intracranial disease who were treated between 2007 and 2018. Kaplan-Meier estimates of overall survival (OS) and progression-free survival (PFS) were calculated and multivariate Cox proportional hazards models were generated. The cumulative incidence of brain metastases was estimated using competing risks methodology.ResultsNinety-two patients were identified without intracranial disease at initial staging, 39 of whom received PCI. Median follow-up was 56.7 months. The median OS for the cohort was 35.5 months (95% CI, 25.8-49.3), and median PFS was 19.1 months (95% CI, 12.3-30.5). Median OS with PCI versus observation was 37.9 months (95% CI, 31.8-not reached) versus 30.5 months (95% CI, 14.6-56.1; P = .07), whereas median PFS was 26.3 months (95% CI 19.1-not reached) versus 12.3 months (95% CI, 8.5-30.5; P = .02), respectively. Overall, at 2 years, the cumulative incidence of brain metastases was 10% with PCI and 29% without; this increased to 32% and 29% by 4 years (P = .66). In those patients who had negative magnetic resonance imaging of the brain after completing initial treatment, the 1-year cumulative incidence of brain metastasis was not significantly different at 8% versus 11% (P = .46) respectively. Both PCI and treatment response were independent predictors for PFS on multivariate analysis. Stratified by disease response, patients with a complete response did not benefit from PCI (P = .50), whereas those with partial response or stable disease experienced improved PFS (P = .01).ConclusionsOverall, PCI was associated with improved PFS and reduced early incidence of brain metastases. Patients achieving a complete response to initial therapy did not experience a PFS benefit with PCI. This may indicate that subsets of LS-SCLC patients can potentially be spared from PCI in the era of modern imaging.     

Involvement of <Emphasis Type="Italic">17β-hydroxysteroid dehydrogenase type</Emphasis> gene <Emphasis Type="Italic">1</Emphasis> 937 A&gt;G polymorphism in infertility in Polish Caucasian women with endometriosis

Purpose

Endometriosis is considered to be an estrogen-related chronic inflammatory disease. The 17β-hydroxysteroid dehydrogenase 1 (HSD17B1) converts estrone to 17β estradiol. The role of HSD17B1 937 A>G (rs605059) single nucleotide polymorphism (SNP) in development of endometriosis is still disputable. This study evaluated the association of the HSD17B1 937 A>G (rs605059) SNP with infertile women affected by endometriosis from Polish Caucasian population.

Methods

The genotyping of cases (n = 290) and fertile women (n = 410) was conducted by high-resolution melting curve analysis.

Results

Statistical analysis demonstrated that the HSD17B1 937 A>G SNP is associated with endometriosis in stages I and II. The p _trend and p _allelic values calculated for the HSD17B1 937 A>G polymorphism were statistically significant and were equal to 0.001 and 0.0009, respectively. There was a significant association for the dominant model: (AG + GG vs AA) OR = 1.973 (95% CI = 1.178–3.304), p = 0.009, and for the recessive model: (GG vs AG + AA) OR = 1.806 (95% CI = 1.178–2.770), p = 0.006. However, we did not find statistical association of HSD17B1 937 A>G polymorphism with all infertile women with endometriosis or infertile women with endometriosis in stages III and IV.

Conclusion

Our genetic study demonstrated HSD17B1 937 G variant as a risk factor for infertility in women with stage I and II endometriosis in Polish Caucasian patients.

     

Phase Analysis and Thermoelectric Properties of Cu-Rich Tetrahedrite Prepared by Solvothermal Synthesis

Because of the large Seebeck coefficient, low thermal conductivity, and earth-abundant nature of components, tetrahedrites are promising thermoelectric materials. DFT calculations reveal that the additional copper atoms in Cu-rich Cu₁₄Sb₄S₁₃ tetrahedrite can effectively engineer the chemical potential towards high thermoelectric performance. Here, the Cu-rich tetrahedrite phase was prepared using a novel approach, which is based on the solvothermal method and piperazine serving both as solvent and reagent. As only pure elements were used for the synthesis, the offered method allows us to avoid the typically observed inorganic salt contaminations in products. Prepared in such a way, Cu₁₄Sb₄S₁₃ tetrahedrite materials possess a very high Seebeck coefficient (above 400 μVK⁻¹) and low thermal conductivity (below 0.3 Wm⁻¹K⁻¹), yielding to an excellent dimensionless thermoelectric figure of merit ZT ≈ 0.65 at 723 K. The further enhancement of the thermoelectric performance is expected after attuning the carrier concentration to the optimal value for achieving the highest possible power factor in this system.     

APTES-Modified SBA-15 as a Non-Toxic Carrier for Phenylbutazone

Improvement of the bioavailability of poorly soluble medicinal substances is currently one of the major challenges for pharmaceutical industry. Enhancing the dissolution rate of those drugs using novel methods allows to increase their bioavailability. In recent years, silica-based mesoporous materials have been proposed as drug delivery systems that augment the dissolution rate. The aim of this study was to analyse the influence of phenylbutazone adsorption on SBA-15 on its dissolution rate. Moreover, we examined the cytotoxicity of the analyzed silica. The material was characterized by SEM, TEM, DSC, ¹H-NMR, XRD, and FT-IR. The phenylbutazone did not adsorb on unmodified SBA-15, while the adsorption on APTES-modified SBA-15 resulted in 50.43 mg/g of loaded phenylbutazone. Phenylbutazone adsorbed on the APTES-modified SBA-15 was then released in the hydrochloric acidic medium (pH 1.2) and phosphate buffer (pH 7.4) and compared to the dissolution rate of the crystalline phenylbutazone. The release profiles of the amorphous form of adsorbed phenylbutazone are constant in different pH, while the dissolution rate of the crystalline phenylbutazone depends on the pH. The cytotoxicity assays were performed using the Caco-2 cell line. Our results indicate that the analyzed material ensured phenylbutazone adsorption in an amorphous state inside the mesopores and increased its dissolution rate in various pH levels. Furthermore, the cytotoxicity assay proved safety of studied material. Our study demonstrated that APTES-modified SBA-15 can serve as a non-toxic drug carrier that improves the bioavailability of phenylbutazone.     

A follow-up study of infants with intracranial hemorrhage at full-term

OBJECTIVE: To determine physical and cognitive outcomes of full-term infants who suffered intracranial hemorrhage (ICH) at birth. METHODS: A retrospective hospital-based, follow-up study of infants treated in London, Ontario between 1985 and 1996. Follow-up was conducted by telephone interviews and clinic visits. Outcome was measured according to physical and cognitive scales. Perinatal risk factors and hemorrhage characteristics were correlated with final outcome. RESULTS: For this study 66 infants with ICH were identified, of which seven died during the first week of life. We obtained follow-up in all but ten cases (median = 3-years; range 1.0 to 10.9 years). Overall, 57% of infants had no physical or cognitive deficits at follow-up. Death occurred most frequently among those with primarily subarachnoid hemorrhage (19%) and the most favorable outcomes occurred among those with subdural hemorrhage (80% had no disability). In univariate models, thrombocytopenia (platelet count < or = 70 x 10(9)/L), increasing overall hemorrhage severity, frontal location and spontaneous vaginal delivery as opposed to forceps-assisted delivery increased risk for poor outcome. In multivariate models, all these factors tended towards increased risk, but only thrombocytopenia remained significant for physical disability (OR = 7.6; 95% CI = 1.02 - 56.6); thrombocytopenia was borderline significant in similar models for cognitive disability (OR = 4.6; 95% CI = 0.9 - 23.9). CONCLUSION: Although forceps-assisted delivery may contribute to ICH occurrence, our study found better outcomes among these infants than those who had ICH following a spontaneous vaginal delivery. Hemorrhage in the frontal lobe was the most disabling hemorrhage location and if multiple compartments were involved, disability was also more likely to occur. However, in this report we found that the factor that was most likely to contribute to poor outcome was thrombocytopenia and this remained important in multivariate analysis.     

Conservative management after prenatal ultrasound diagnosis of meconium periorchitis

Meconium periorchitis is caused by the leakage of meconium from a bowel perforation into the peritoneal cavity via a patent processus vaginalis into the scrotal sac during fetal life or in the early postnatal period. Intrauterine meconium peritonitis causes sterile inflammatory response and calcification. Here, we describe a prenatally diagnosed case of meconium periorchitis. During the ultrasound scan at 29 weeks’ gestation, enlargement of the scrotum with many small hyperechogenic masses and normal anatomy of testis was observed. Our case is the 11th prenatally diagnosed case presented in the worldwide literature and the first one described in Poland. This case confirms the latest tendency for the conservative management of meconium periorchitis and an asymptomatic postnatal course.