Immunosuppressive Therapy After Autologous Hematopoietic Stem Cell Transplantation in Systemic Sclerosis Patients—High Efficacy of Rituximab

BackgroundSystemic sclerosis (SSc) patients often need immunosuppressive medication (IS) for disease control. If SSc is progressive despite IS, autologous hematopoietic stem cell transplantation (aHSCT) is a treatment option for selected SSc patients. aHSCT is effective with good available evidence, but not all patients achieve a treatment-free remission after aHSCT. Thus far, data about the need of IS after aHSCT in SSc is not published. The aim of this study was to investigate the use of IS after aHSCT, its efficacy, and the occurrence of severe adverse events (SAEs).MethodsTwenty-seven patients with SSc who had undergone aHSCT were included in this single-center retrospective cohort study. Clinical data, including IS, SAEs, and lung function data, were collected.ResultsSixteen of 27 (59.3%) patients received IS after aHSCT. Methotrexate, rituximab, mycophenolate, cyclophosphamide, and hydroxychloroquine were most commonly used. The main reason for starting IS was SSc progress. Nine patients received rituximab after aHSCT and showed an improvement in modified Rodnan skin score and a stabilization of lung function 2 years after rituximab. SAEs in patients with IS after aHSCT (50.0%) were not more common than in patients without IS (54.6%). SAEs were mostly due to SSc progress, secondary autoimmune diseases, or infections. Two deaths after aHSCT were transplantation related and three during long-term follow-up due to pulmonary arterial hypertension.ConclusionDisease progression and secondary autoimmune diseases may necessitate IS after aHSCT in SSc. Rituximab seems to be an efficacious treatment option in this setting. Long-term data on the safety of aHSCT is reassuring.

Trans-Catheter Valve-in-Valve Implantation for the Treatment of Aortic Bioprosthetic Valve Failure

Aortic valve-in-valve (ViV) procedure is a valid treatment option for patients affected by bioprosthetic heart valve (BHV) degeneration. However, ViV implantation is technically more challenging compared to native trans-catheter aortic valve replacement (TAVR). A deep knowledge of the mechanism and features of the failed BHV is pivotal to plan an adequate procedure. Multimodal imaging is fundamental in the diagnostic and pre-procedural phases. The main challenges associated with ViV TAVR consist of a higher risk of coronary obstruction, severe post-procedural patient-prosthesis mismatch, and a difficult coronary re-access. In this review, we describe the principles of ViV TAVR.

Efficacy and Safety of Trans-Arterial Yttrium-90 Radioembolization in Patients with Unresectable Liver-Dominant Metastatic or Primary Hepatic Soft Tissue Sarcomas

Patients with liver-dominant metastatic or primary hepatic soft tissue sarcomas (STS) have poor prognosis. Surgery can prolong survival, but most patients are not surgical candidates, and treatment response is limited with systemic chemotherapy. Liver-directed therapies have been increasingly employed in this setting, and Yttrium-90 trans-arterial radioembolization (TARE) is an understudied yet promising treatment option. This is a retrospective analysis of 35 patients with metastatic or primary hepatic STS who underwent TARE at a single institution between 2006 and 2020. The primary outcomes that were measured were overall survival (OS), liver progression-free survival (LPFS), and radiologic tumor response. Clinical and biochemical toxicities were assessed 3 months after the procedure. Median OS was 20 months (95% CI: 13.9–26.1 months), while median LPFS was 9 months (95% CI: 6.2–11.8 months). The objective response rate was 56.7%, and the disease control rate was 80.0% by mRECIST at 3 months. The following correlated with better OS post-TARE: liver disease control (DC) at 6 months (median OS: 40 vs. 17 months, p = 0.007); LPFS ≥ 9 months (median OS: 50 vs. 8 months, p < 0.0001); ECOG status 0–1 vs. 2 (median OS: 22 vs. 6 months, p = 0.042); CTP class A vs. B (median OS: 22 vs. 6 months, p = 0.018); and TACE post-progression (median OS: 99 vs. 16 months, p = 0.003). The absence of metastases at diagnosis was correlated with higher median LPFS (7 vs. 1 months, p = 0.036). Two grade 4 (5.7%) and ten grade 3 (28.6%) laboratory toxicities were identified at 3 months. There was one case of radioembolization-induced liver disease and two cases of radiation-induced peptic ulcer disease. We concluded that TARE could be an effective and safe treatment option for patients with metastatic or primary hepatic STS with good tumor response rates, low incidence of severe toxicity, and longer survival in patients with liver disease control post-TARE.

Topical Drug Delivery to the Posterior Segment of the Eye

Topical drug delivery to the posterior segment of the eye is a very complex challenge. However, topical delivery is highly desired, to achieve an easy-to-use treatment option for retinal diseases. In this review, we focus on the drug characteristics that are relevant to succeed in this challenge. An overview on the ocular barriers that need to be overcome and some relevant animal models to study ocular pharmacokinetics are given. Furthermore, a summary of substances that were able to reach the posterior segment after eye drop application is provided, as well as an outline of investigated delivery systems to improve ocular drug delivery. Some promising results of substances delivered to the retina suggest that topical treatment of retinal diseases might be possible in the future, which warrants further research.

Interventional Bronchus Occlusion Using Amplatzer Devices – A Promising Treatment Option for Children with Persistent Air Leak

Background: Persistent air leak (PAL) is a severe complication of secondary spontaneous pneumothorax (SSP). Surgical interventions are usually successful when medical treatment fails, but can be associated with significant complications and loss of potentially recoverable lung parenchyma. Methods: Retrospective analysis of efficacy and safety of interventional bronchus occlusions (IBO) using Amplatzer devices (ADs) in children with PAL secondary to SSP. Results: Six patients (four males, 4–15 years of age) underwent IBO using ADs as treatment for PAL. Necrotizing pneumonia (NP) was the most common cause (n=4) of PAL. Three patients were previously healthy and three suffered from chronic lung disease. All patients required at least two chest tubes prior to the intervention for a duration of 15–43 days and all required oxygen or higher level of ventilatory support. In three cases, previous surgical interventions had been performed without success. All children improved after endobronchial intervention and we observed no associated complications. All chest tubes were removed within 5–25 days post IBO. In patients with PAL related to NP (n=4), occluders were removed bronchoscopically without re-occurrence of pneumothorax after a mean of 70 days (IQR: 46.5–94). Conclusion: IBO using ADs is a safe and valuable treatment option in children with PAL independent of disease severity and underlying cause. A major advantage of this procedure is its less invasiveness compared to surgery and the parenchyma- preserving approach.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in Gastric Cancer with Peritoneal Metastasis—Indian Experience

Introduction Peritoneal metastasis secondary to gastric cancer is associated with poor prognosis. Recent studies have shown that cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may be an efficacious treatment option for an otherwise palliative condition. Methods A retrospective single institutional study of patents diagnosed with gastric carcinoma and peritoneal metastasis and treated with CRS and HIPEC from February 2015 to December 2019. Results Sixteen patients with gastric cancer and peritoneal carcinomatosis were treated with CRS and HIPEC. Three patients underwent upfront surgery, and five patients underwent interval surgery. The mean peritoneal cancer index (PCI) was 3.5, and adequate complete cytoreduction (CC) score of 0/1 was achieved in all patients. All patients received HIPEC with mitomycin C. Major surgical complications were in 12.5% of patients. Grade I surgical site infection was present in one patient. Three patients had prolonged gastrointestinal (GI) recovery. The 30-day mortality was zero. Median follow-up time was 39 months. The median progression-free survival (PFS) was 12 months (95% confidence interval [CI] 6.86–17.13). The median overall survival (OS) was 17 months (95% CI 6.36–27.64). Conclusion Multidisciplinary treatment of perioperative chemotherapy with CRS and HIPEC is a promising treatment option, which may prolong survival in selected patients, and large randomized clinical trials are warranted for it to become standard of care.