Treatments after Immune Checkpoint Inhibitors in Patients with dMMR/MSI Metastatic Colorectal Cancer

Background: Several studies reported improved outcomes with conventional treatments (CT, i.e., chemotherapy ± targeted therapy) administered after immune checkpoints inhibitors (ICI) in certain tumor types. No data are available concerning patients (pts) with metastatic colorectal cancer (mCRC) harboring mismatch repair deficiency/microsatellite instability (dMMR/MSI). We aimed to assess the outcomes of dMMR/MSI mCRC pts receiving CT after ICI failure. Methods: We conducted a retrospective multicenter study investigating the outcomes of all dMMR/MSI mCRC pts who received post-ICI CT between 2015 and 2020. Results: 31 pts (male 61%, median age 56 years) were included. ICI was an anti-PD(L)1 monotherapy in 71% of pts, and 61% received >2 lines before post-ICI CT. The overall response rate and disease control rate were 13% and 45%, with a median progression-free survival (PFS) and overall survival of 2.9 and 7.4 months, respectively. No association of the outcomes with either ICI efficacy or anti-angiogenic agents was observed. Prolonged PFS (range 16.1–21.3 months) was observed in 4 pts (13%). Conclusions: Although conducted on a limited number of patients, our results do not support an association of previous ICI treatment with an enhanced efficacy of CT in dMMR/MSI mCRC. However, prolonged disease control was observed in several cases, suggesting that some pts might derive an unexpected benefit from post-ICI treatments.

Cisplatin and Irinotecan as First-Line Chemotherapy for Previously Untreated Metastatic Thymic Carcinoma: Updated Analysis

Platinum-based chemotherapy is the de facto standard treatment for metastatic or unresectable thymic carcinoma. The optimal chemotherapy regimen has not yet been determined, including whether this should be combined with a second- or third-generation anti-cancer agent. We retrospectively evaluated the data of patients with metastatic or unresectable thymic carcinoma who were treated with a combination of cisplatin and irinotecan as first-line chemotherapy between 2002 and 2021 (trial registration UMIN000012175). The primary endpoint was response rate according to the RECIST criteria version 1.1. Secondary endpoints were disease control rate, progression-free survival (PFS), overall survival (OS), and toxicity (adverse events). Some patients analyzed in this study were also included in the previous trial, which was terminated early. For this analysis, we included 18 patients with a median age of 56 years and an Eastern Cooperative Oncology Group performance status of 0 or 1. All patients had clinical stage IVa or IVb thymic carcinoma according to the Masaoka-Koga staging system. The response rate was 44% and the disease control rate was 89%. The median PFS was 8.4 months (95% confidence interval (CI): 2.7–11.6 months) and the median OS was 45.6 months (95% CI: 15.7–69.1 months). Grade 3 or worse hematological toxicity was observed in 5 patients and grade 3 or worse non-hematological toxicity was observed in 3 patients. None of the patients developed febrile neutropenia, and no treatment-related deaths occurred. Thus, the combination of cisplatin and irinotecan as first-line chemotherapy for metastatic thymic carcinoma showed efficacy and acceptable toxicity.

Trait-Based Vaccination of Individual Meerkats (Suricata suricatta) against Tuberculosis Provides Evidence to Support Targeted Disease Control

Individuals vary in their potential to acquire and transmit infections, but this fact is currently underexploited in disease control strategies. We trialled a trait-based vaccination strategy to reduce tuberculosis in free-living meerkats by targeting high-contact meerkats (socially dominant individuals) in one study arm, and high-susceptibility individuals (young subordinates) in a second arm. We monitored infection within vaccinated groups over two years comparing the results with untreated control groups. Being a member of a high-contact group had a protective effect on individuals’ survival times (Hazard Ratio = 0.5, 95% Confidence Interval, CI: 0.29–0.88, p = 0.02) compared to control groups. Over the study, odds of testing positive for tuberculosis increased more than five-fold in control groups (Odds Ratio = 5.40, 95% CI = 0.94–30.98, p = 0.058); however, no increases were observed in either of the treatment arms. Targeted disease control approaches, such as the one described in this study, allow for reduced numbers of interventions. Here, trait-based vaccination was associated with reduced infection rates and thus has the potential to offer more efficient alternatives to traditional mass-vaccination policies. Such improvements in efficiency warrant further study and could make infectious disease control more practically achievable in both animal (particularly wildlife) and human populations.

Peripheral ulcerative keratitis: A review of aetiology and management

Background: Peripheral ulcerative keratitis (PUK) is a severe inflammatory disease of the peripheral cornea that can be caused by local factors or systemic inflammatory disease.Aim: The purpose of this review is to give an overview of the pathophysiology, aetiology, clinical features, diagnosis, and management of PUK.Method: A PubMed search was conducted using the keywords, ‘peripheral ulcerative keratitis’ and ‘Mooren’s ulcer’.Results: The peripheral cornea has unique characteristics the predispose to the development of PUK. These include fine capillary arcades that allow for deposition of immune complexes and subsequent activation of an inflammatory cascade with corneal melt. Several conditions have been implicated in the aetiology of PUK. The most commonly cited causes are rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA) and various dermatoses. In patients with RA, PUK usually presents in established disease, whereas in GPA, PUK may be the presenting feature in up to 60% of cases. In RA it heralds the onset of a systemic vasculitis with significant associated morbidity and mortality. The management of PUK follows an individualised stepwise approach. All patients require supportive measures to encourage healing and halt the process of keratolysis. Systemic autoimmune conditions need a systemic corticosteroid as a fast-acting agent to halt the inflammatory process while cytotoxic therapy maintains long term disease control. Failure to achieve disease control with CTT, necessitates the use of a biologic agent.Conclusion: Peripheral ulcerative keratitis is a severe inflammatory disease of the peripheral cornea that needs a thorough diagnostic workup and stepwise management approach.

2021 CDC Update: Treatment and Complications of Sexually Transmitted Infections (STIs)

The Centers for Disease Control and Prevention (CDC) recently updated their Sexually-Transmitted Infection (STI) Treatment Guidelines with a revision to the approach to gonococcal infections in December 2020 and other STIs in July 2021. This article reviews the new recommendations and highlights important updates from the 2015 iteration that are crucial for primary care and community health practice.

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.

A novel risk score for disease control prediction of Chronic rhinosinusitis

Objectives: To assess the impact of risk factors on the disease control among CRS patients, following 1 year of functional endoscopic sinus surgery (FESS), and combining the risk factors to formulate a convenient, visualized prediction model. Design: A retrospective and nonconcurrent cohort study Setting and Participants: A total of 325 patients with Chronic rhinosinusitis (CRS) from June 2018 to July 2020 at the First Affiliated Hospital, the Third Affiliated Hospital, and the Seventh Affiliated Hospital of Sun Yat-sen University. Main Outcomes Measures: Outcomes were time to event measures: the disease control of CRS after surgery 1 year. The presence of nasal polyps, smoking habits, allergic rhinitis (AR), the ratio of tissue eosinophil (TER), and peripheral blood eosinophil count (PBEC)and asthma was assessed. The logistic regression models were used to conduct multivariate and univariate analyses. Asthma, TER, AR, PBEC were also included in the nomogram. The calibration curve and AUC (Area Under Curve) were used to evaluate the forecast performance of the model. Results: In univariate analyses, most of the covariates had significant associations with the endpoints, except for age, gender, and smoking. The nomogram showed the highest accuracy with an AUC of 0.760 (95% CI, 0.688-0.830) in the training cohort. Conclusions: In this cohort study that included the asthma, AR, TER, PBEC had significantly affected the disease control of CRS after surgery. The model provided relatively accurate prediction in the disease control of CRS after FESS and served as a visualized reference for daily diagnosis and treatment.