Mediastinal irradiation and valvular heart disease.

Anticancer therapy has the potential to cause unwanted cardiovascular side effects. Utilization of radiation therapy to treat tumors near the heart can result in radiation-induced valvular heart disease among other cardiovascular pathologies. The aim of this review is to describe the epidemiology, pathophysiology, risk prediction, non-invasive imaging modalities and management of radiation-induced valvular heart disease with a focus on pre-operative risk assessment and contemporary treatment options.

Outcomes of acute pulmonary embolism in hospitalized patients with cancer.

BACKGROUND: Cancer-associated pulmonary embolism (PE) places a significant burden on patients and health care systems. METHODS: A retrospective cross-sectional analysis of the National Inpatient Sample (NIS) database was performed in patients with acute PE from 2002 to 2014. Among patients hospitalized with PE, we investigated the differences in clinical outcomes and healthcare utilization in patients with and without cancer. A multivariate logistic regression model was applied to calculate adjusted odds ratios (OR) to estimate the impact of cancer on clinical outcomes. Wilcoxon rank sum tests were used to determine the differences in healthcare utilization between the two cohorts. RESULTS: Among 3,313,044 patients who were discharged with a diagnosis of acute PE, 84.2% did not have cancer, while 15.8% had cancer as a comorbidity (56% metastatic cancer, 35% solid tumor without metastasis, and 9% lymphoma). Patients with cancer had a higher mean age but lower rates of common comorbidities except for coagulation deficiency than patients without a cancer diagnosis. In patients with cancer, the rate of IVC filter placement was higher (21.7% vs. 13.11%, OR 1.76 (95% CI 1.73-1.79); p < 0.0001) and thrombolytic use lower (1.34% vs. 2.15%, OR 0.68 (95% CI 0.64-0.72); p < 0.0001). Patients with cancer hospitalized for PE had a higher all-cause in-hospital mortality (11.8% vs. 6.6%, OR 1.79 (95% CI 1.75-1.83); p < 0.0001), longer length of stay (6 vs. 5 days; p < 0.0001), higher total charge per hospitalization ($30,885 vs. $27,273; p < 0.0001), and higher rates of home health services upon discharge (35.8% vs. 23.2%; p < 0.0001) compared with those without cancer. CONCLUSION: Concurrent cancer diagnosis in patients hospitalized for acute PE was associated with a 90% increase in all-cause mortality, longer length of stay, higher total charge per hospitalization, and higher rates of home health services upon discharge. The majority (56%) of patients with cancer had metastatic disease. Furthermore, there were identifiable differences in the intervention for acute PE between the two groups.

Response with pembrolizumab in a patient with EGFR mutated non-small cell lung cancer harbouring insertion mutations in V834L and L858R.

INTRODUCTION: Lung cancer is the leading cause of cancer-related deaths with non-small cell lung cancer (NSCLC) being the most common of them. About a third of NSCLC cases have an epidermal growth factor (EGFR) mutation, which is usually susceptible to tyrosine kinase inhibitors (TKIs). In rare cases where patients progress through TKI therapy, the use of immune checkpoint inhibitors (ICIs) remains controversial. CASE REPORT: We describe a case of a patient with significant history of smoking and EGFR mutated programmed death ligand-1 (PD-L1) positive NSCLC who was initially treated with TKI therapy. MANAGEMENT/OUTCOME: While patient progressed on TKI therapy, he was able to achieve a durable response with a single PD-L1 agent, pembrolizumab. Contrary to the available evidence, the presented EGFR mutant NSCLC responded to PD-L1 pathway inhibition. DISCUSSION: From our observation Pembrolizumab could be promising in patients with rare EGFR mutations who do not respond to EGFR directed therapy. Our report provides supporting data for the use of immunotherapies in patients with EGFR mutated NSCLC.

Subdural Hemorrhage Due to Acquired Von Willebrand Syndrome in a Patient With Polycythemia Vera.

Polycythemia vera (PV) is a chronic myeloproliferative neoplasm associated with thrombosis. A 48-year-old female with PV presented with right eye pain following a low-impact head trauma. She consumed aspirin for analgesia and took preparations of Chinese herbs. CT head revealed right-sided subdural hematoma. She had reduced Von Willebrand activity to 26%. Direct angiographic imaging showed an aneurysm arising from a right middle cerebral atery (MCA) branch. The patient was given 1-deamino-8-D-arginine vasopressin (DDAVP) prior to the craniotomy. Intra-operative examination revealed that the aneurysm-like structure was a small grape-like structure of the fibrinous part of the subdural membrane that had formed from the subdural hematoma. Acquired von Willebrand syndrome (AVWS) is an important risk factor for bleeding in PV. DDAVP may be useful to increase levels of Von Willebrand Factor (VWF) and decrease the risk of bleeding perioperatively. Exogenous substances such as ginseng should be investigated as possible contributors to bleeding tendency and discontinued.

Lactate Dehydrogenase A Depletion Alters MyC-CaP Tumor Metabolism, Microenvironment, and CAR T Cell Therapy.

To enhance human prostate-specific membrane antigen (hPSMA)-specific chimeric antigen receptor (CAR) T cell therapy in a hPSMA+ MyC-CaP tumor model, we studied and imaged the effect of lactate dehydrogenase A (LDH-A) depletion on the tumor microenvironment (TME) and tumor progression. Effective LDH-A short hairpin RNA (shRNA) knockdown (KD) was achieved in MyC-CaP:hPSMA+ Renilla luciferase (RLuc)-internal ribosome entry site (IRES)-GFP tumor cells, and changes in tumor cell metabolism and in the TME were monitored. LDH-A downregulation significantly inhibited cell proliferation and subcutaneous tumor growth compared to control cells and tumors. However, total tumor lactate concentration did not differ significantly between LDH-A knockdown and control tumors, reflecting the lower vascularity, blood flow, and clearance of lactate from LDH-A knockdown tumors. Comparing treatment responses of MyC-CaP tumors with LDH-A depletion and/or anti-hPSMA CAR T cells showed that the dominant effect on tumor growth was LDH-A depletion. With anti-hPSMA CAR T cell treatment, tumor growth was significantly slower when combined with tumor LDH-A depletion and compared to control tumor growth (p < 0.0001). The lack of a complete tumor response in our animal model can be explained in part by (1) the lower activity of human CAR T cells against hPSMA-expressing murine tumors in a murine host, and (2) a loss of hPSMA antigen from the tumor cell surface in progressive generations of tumor cells.

Interventions for acne scars.

BACKGROUND: Acne scarring is a frequent complication of acne and resulting scars may negatively impact on an affected person's psychosocial and physical well-being. Although a wide range of interventions have been proposed, there is a lack of high-quality evidence on treatments for acne scars to better inform patients and their healthcare providers about the most effective and safe methods of managing this condition. This review aimed to examine treatments for atrophic and hypertrophic acne scars, but we have concentrated on facial atrophic scarring. OBJECTIVES: To assess the effects of interventions for treating acne scars. SEARCH METHODS: We searched the following databases up to November 2015: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library (2015, Issue 10), MEDLINE (from 1946), EMBASE (from 1974), and LILACS (from 1982). We also searched five trials registers, and checked the reference lists of included studies and relevant reviews for further references to randomised controlled trials. SELECTION CRITERIA: We include randomised controlled trials (RCTs) which allocated participants (whether split-face or parallel arms) to any active intervention (or a combination) for treating acne scars. We excluded studies dealing only or mostly with keloid scars. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data from each of the studies included in this review and evaluated the risks of bias. We resolved disagreements by discussion and arbitration supported by a method expert as required. Our primary outcomes were participant-reported scar improvement and any adverse effects serious enough to cause participants to withdraw from the study. MAIN RESULTS: We included 24 trials with 789 adult participants aged 18 years or older. Twenty trials enrolled men and women, three trials enrolled only women and one trial enrolled only men. We judged eight studies to be at low risk of bias for both sequence generation and allocation concealment. With regard to blinding we judged 17 studies to be at high risk of performance bias, because the participants and dermatologists were not blinded to the treatments administered or received; however, we judged all 24 trials to be at a low risk of detection bias for outcome assessment. We evaluated 14 comparisons of seven interventions and four combinations of interventions. Nine studies provided no usable data on our outcomes and did not contribute further to this review's results.For our outcome 'Participant-reported scar improvement' in one study fractional laser was more effective in producing scar improvement than non-fractional non-ablative laser at week 24 (risk ratio (RR) 4.00, 95% confidence interval (CI) 1.25 to 12.84; n = 64; very low-quality evidence); fractional laser showed comparable scar improvement to fractional radiofrequency in one study at week eight (RR 0.78, 95% CI 0.36 to 1.68; n = 40; very low-quality evidence) and was comparable to combined chemical peeling with skin needling in a different study at week 48 (RR 1.00, 95% CI 0.60 to 1.67; n = 26; very low-quality evidence). In a further study chemical peeling showed comparable scar improvement to combined chemical peeling with skin needling at week 32 (RR 1.24, 95% CI 0.87 to 1.75; n = 20; very low-quality evidence). Chemical peeling in one study showed comparable scar improvement to skin needling at week four (RR 1.13, 95% CI 0.69 to 1.83; n = 27; very low-quality evidence). In another study, injectable fillers provided better scar improvement compared to placebo at week 24 (RR 1.84, 95% CI 1.31 to 2.59; n = 147 moderate-quality evidence).For our outcome 'Serious adverse effects' in one study chemical peeling was not tolerable in 7/43 (16%) participants (RR 5.45, 95% CI 0.33 to 90.14; n = 58; very low-quality evidence).For our secondary outcome 'Participant-reported short-term adverse events', all participants reported pain in the following studies: in one study comparing fractional laser to non-fractional non-ablative laser (RR 1.00, 95% CI 0.94 to 1.06; n = 64; very low-quality evidence); in another study comparing fractional laser to combined peeling plus needling (RR 1.00, 95% CI 0.86 to 1.16; n = 25; very low-quality evidence); in a study comparing chemical peeling plus needling to chemical peeling (RR 1.00, 95% CI 0.83 to 1.20; n = 20; very low-quality evidence); in a study comparing chemical peeling to skin needling (RR 1.00, 95% CI 0.87 to 1.15; n = 27; very low-quality evidence); and also in a study comparing injectable filler and placebo (RR 1.03, 95% CI 0.10 to 11.10; n = 147; low-quality evidence).For our outcome 'Investigator-assessed short-term adverse events', fractional laser (6/32) was associated with a reduced risk of hyperpigmentation than non-fractional non-ablative laser (10/32) in one study (RR 0.60, 95% CI 0.25 to 1.45; n = 64; very low-quality evidence); chemical peeling was associated with increased risk of hyperpigmentation (6/12) compared to skin needling (0/15) in one study (RR 16.00, 95% CI 0.99 to 258.36; n = 27; low-quality evidence). There was no difference in the reported adverse events with injectable filler (17/97) compared to placebo (13/50) (RR 0.67, 95% CI 0.36 to 1.27; n = 147; low-quality evidence). AUTHORS' CONCLUSIONS: There is a lack of high-quality evidence about the effects of different interventions for treating acne scars because of poor methodology, underpowered studies, lack of standardised improvement assessments, and different baseline variables.There is moderate-quality evidence that injectable filler might be effective for treating atrophic acne scars; however, no studies have assessed long-term effects, the longest follow-up being 48 weeks in one study only. Other studies included active comparators, but in the absence of studies that establish efficacy compared to placebo or sham interventions, it is possible that finding no evidence of difference between two active treatments could mean that neither approach works. The results of this review do not provide support for the first-line use of any intervention in the treatment of acne scars.Although our aim was to identify important gaps for further primary research, it might be that placebo and or sham trials are needed to establish whether any of the active treatments produce meaningful patient benefits over the long term.

Intravitreal phacoemulsification with pars plana vitrectomy for management of posteriorly dislocated nucleus or lens fragments.

PURPOSE: Dislocation of crystalline lens nucleus/fragments into the vitreous cavity during phacoemulsification is a potentially serious, sight-threatening, uncommon complication of cataract surgery. It is associated with significant intraocular inflammation and can lead to poor visual outcome. The current study assesses the outcome of immediate intravitreal phacoemulsification with pars plana vitrectomy in management of posteriorly dislocated nucleus/lens fragments. METHODS: In this retrospective case series, records of 23 patients who underwent immediate pars plana vitrectomy and intravitreal phacoemulsification for removal of dislocated nucleus/lens fragments at the same sitting of phacoemulsification were reviewed. Data including patients' preoperative and postoperative vision and intraoperative and postoperative complications were recorded. RESULTS: The mean follow-up period was 16.5 months (range, 5-31 months). Preoperative visual acuity ranged from 0.05 to 0.5. The final postoperative visual acuity ranged between HM and 1.0. Fifty-two percent of eyes (12 eyes) had a final postoperative visual acuity of 0.5 or better. Complications included 2 cases of cystoid macular edema and 2 cases of retinal detachment. CONCLUSIONS: Immediate vitrectomy and intravitreal phacoemulsification is a surgical option in the management of posteriorly dislocated nucleus/lens fragments without much risk of retinal damage. It is relatively safe and most patients achieved a good visual outcome. The risk of postoperative complications including uveitis, secondary glaucoma, and cystoid macular edema could be minimized.