The importance of correctly timing cancer immunotherapy

Introduction: The treatment options for cancer—surgery, radiotherapy and chemotherapy—are now supplemented with immunotherapy. Previously underappreciated but now gaining strong interest are the immune modulatory properties of the three conventional modalities. Moreover, there is a better understanding of the needs and potential of the different immune therapeutic platforms. Key to improved treatment will be the combinations of modalities that complete each other’s shortcomings.

Area covered: Tumor-specific T-cells are required for optimal immunotherapy. In this review, the authors focus on the correct timing of different types of chemotherapeutic agents or immune modulators and immunotherapeutic drugs, not only for the activation and expansion of tumor-specific T-cells but also to support and enhance their anti-tumor efficacy.

Expert opinion: At an early phase of disease, clinical success can be obtained using single treatment modalities but at later disease stages, combinations of several modalities are required. The gain in success is determined by a thorough understanding of the direct and indirect immune effects of the modalities used. Profound knowledge of these effects requires optimal tuning of immunomonitoring. This will guide the appropriate combination of treatments and allow for correct sequencing the order and interval of the different therapeutic modalities.     

Prednisone dosing per body weight or body surface area in children with nephrotic syndrome—is it equivalent?

The current guidelines recommend a dosage of prednisone of 60 mg/m² body surface area per day (BSA PRED) for the initial therapy of nephrotic syndrome (NS). Alternatively, a dosage of 2 mg/kg body weight per day (W PRED) can be used. We hypothesized that the BSA PRED and W PRED are not equivalent and analyzed the differences between BSA PRED calculated with various formulas for body surface area (BSA), W PRED and the dose of prednisone prescribed for our patients. We performed a retrospective chart review of the patients at their initial presentation of NS. Thirty-three children were included, of median age 3.34 years at presentation. The W PRED was significantly lower than BSA PRED (P < 0.05), with a median W PRED:BSA PRED ratio of 0.85 [interquartile range (IQR) 0.8 to 0.9]. The difference between W PRED and BSA PRED decreased proportionally to patients’ weights up to 30 kg. No differences were noted between the various BSA formulas using both weight and height for the calculation of BSA. The Bland–Altman analysis showed a proportional error between W PRED and BSA PRED up to the average daily dose of 60 mg, with a mean bias of 0.86 (95% limits of agreement = 0.68 to 1.05). Ten out of the 33 patients (30%) were given a lower than recommended BSA PRED dose by more than 5 mg/day. In conclusion, the dosage of prednisone at 2 mg/kg per day versus 60 mg/m² per day is not equivalent for patients with weights <30 kg and/or dose <60 mg/day.     

Does experience with laparoscopic colorectal surgery influence intraoperative outcomes?

Background  This study aimed to define the management and risk factors for intraoperative complications (IOC) and conversion in laparoscopic colorectal surgery, and to assess whether surgeon experience influences intraoperative outcomes. Methods  Consecutive patients undergoing laparoscopic colorectal procedures from 1991 to 2005 were analyzed from a longitudinal prospectively collected database. All patients referred to the four surgeons involved in this study were offered a minimally invasive approach. Patient characteristics, perioperative variables, and surgeon experience data were analyzed and compared. Results  A total of 991 consecutive laparoscopic colorectal procedures were studied. The majority of operations were performed for malignant disease (n = 526, 53%), and most frequently consisted of segmental colonic resections (n = 718, 72%). A total of 85 patients (8.6%) had an IOC. Patients experiencing an IOC had a significantly higher median body weight (75 versus 68 kg, p = 0.0047) and had a higher proportion of previous abdominal surgery (31% versus 20%, p = 0.029). Only 39% of patients suffering an IOC required conversion to open surgery. A total of 126 (13%) cases were converted to open surgery. On multivariable analysis, previous abdominal surgery [odds ratio (OR) 3.40, 95% confidence interval (CI) 1.39–8.35, p = 0.0076] was independently associated with having an IOC and a conversion to open within the same procedure. With increasing experience, individual surgeons were found to operate on heavier patients (p = 0.025), and on patients who had a higher rate of previous intra-abdominal surgery (p < 0.0001). Despite these risk factors, the early and late experience demonstrated no significant difference in terms of IOCs (p = 0.54) and conversion to open surgery (p = 0.40). Conclusions  The majority of IOCs can be managed laparoscopically. With increasing experience surgeons can perform laparoscopic colorectal surgery on a patient population with a greater proportion of previous abdominal surgery and a higher mean body weight without adversely affecting their rates of intraoperative complications or conversion. Oral presentation at the Scientific Session of the Society of American Gastrointestinal and Endoscopic Surgeons, April 12th, 2008, Philadelphia, PA.     

Efficacy of azithromycin versus systemic meglumine antimoniate (Glucantime) in the treatment of cutaneous leishmaniasis

Cutaneous leishmaniasis (CL) treatment is painful, and cosmetic results are often unsatisfying. Azithromycin has been reported to be effective in treatment of CL caused by Leishmania viannia braziliensis. The efficacy of azithromycin was compared with Glucantime in treatment of Old World leishmaniasis. Of 49 patients, 22 received 500 mg/day azithromycin for 5 days/month. Treatment cycles were repeated monthly to a maximum of 4 months; 27 patients received 60 mg/kg intramuscular meglumine antimoniate for 20 days. Both groups were followed up for 16 weeks. In the azithromycin group, 2 patients withdrew because of GI symptoms. The response rates of 20 patients (29 lesions) were as follows: full improvement, 10.3%; partial improvement, 27.6%; and 62.1%, no response. In the glucantime group with 27 patients (58 lesions), these rates were 34.4%, 13.8%, and 51.7%, respectively (P = 0.036). Azithromycin was determined to be not as effective as Glucantime in treatment of Old World CL.     

Evaluation serum levels of Insulin Growth Factor-1 (IGF-1) and its association with clinical parameters in severe COVID-19

Inflammopharmacology - Severe coronavirus disease-2019 (COVID-19) is associated with dysregulated immune response and extreme inflammatory injury. Considering the role of insulin growth factor-1...