Radiotherapy and combination chemotherapy with carmustine,vincristine, and procarbazine (BVP) in primary brain tumors

Summary 26 patients with astrocytoma grade 11–111, and 36 with malignant glioma (astrocytoma grade IV or glioblastoma) were submitted three days after surgery to a cycle of combination chemotherapy, including BCNU, VCR, PCZ (BVP). Eighteen days after surgery, patients received 40 Gy (astrocytoma grade 11–111) or 45 Gy (malignant glioma) of megavoltage whole-brain irradiation, with an additional boost to the tumor bed of 20 Gy, delivered in 6 weeks. Vincristine was injected weekly during radiotherapy. At the end of radiotherapy, patients received BVP every 6 weeks for at least 8 cycles or until a recurrence or progressive disease. Performance status of grade 1 or 2 was achieved in 15 (60%) and in 5 (20%), respectively, of patients with astrocytoma grade 11–111 after 6 months, and in 6 ps. (29%) and in 9 ps. (42%) after 12 months of follow-up. Only 2 (5.5%) and 18 (64%) patients with malignant glioma achieved a performance status of grade 1 or 2 after 6 months, and these proportions are 6% and 35%, respectively, after 12 months. After a 5-year follow-up, 59% of patients with astrocytoma are still alive, with a median survival time of 60+ months, whereas only 4% of patients with malignant glioma are alive, with a median of 11.2 months.     

Urgent desensitization in patients bridged to heart transplantation under extracorporeal membrane oxygenation support: A preliminary experience

Antihuman leukocyte antigen (HLA) antibodies restrict the access to cardiac allografts. Desensitization therapy is a major challenge in patients with cardiogenic shock waiting for urgent heart transplantation (HT). We retrospectively reviewed six patients (mean age of 37.5 years [16–70]) who underwent plasmapheresis (PP) under extracorporeal membrane oxygenation (ECMO) before transplant between January 2017 and September 2018. The average duration of follow‐up was 25 months [20–32]. Mean fluorescence intensity (MFI) of HLA‐specific antibodies was reported as follows: score 4 for MFI < 1000, score 6 for 1000 < MFI < 3000 and score 8 for MFI > 3000. The mean duration of ECMO support was 29 days [1–74] and 6.8 [1–29] PP sessions were performed per patient before transplant. The mean number of HLA‐specific antibodies before HT was 9.6 for score 6 [4–13] and 5.8 for score 8 [1–12]. Four patients had major complications after transplantation (2 hemorrhagic shocks, 5 infectious events). Mean MFI reduction rate was 94% [79–100] for Class I and 44.2% for Class II [0–83]. Hospital survival was 100%, and early antibody‐mediated rejection was diagnosed in one patient at 7 days after HT. Plasmapheresis under ECMO support was associated with favorable early outcomes in highly sensitized candidates for urgent heart transplantation.     

Ipilimumab for the treatment of metastatic prostate cancer

Introduction: Immunotherapy with checkpoint inhibitors is beginning to be recognized as a valid weapon for the treatment of metastatic prostate cancer (PCa) when chemotherapy fails. Ipilimumab (ipi) is a fully humanized monoclonal antibody that blocks the activity of CTLA4. It also has a molecular weight of 148 kDa and is water-soluble at physiological pH. Ipi was first approved by the FDA for the treatment of malignant melanoma and is currently being studied in metastatic castration-resistant prostate cancer, with promising early results.

Areas covered: The aim of this review is to collate the most significant preclinical and clinical studies available that look at ipi to propose new strategies for the future.

Expert opinion: Additional studies are required to reduce toxicity and increase the activity of ipi in PCa. A possible strategy is to combine ipi with standard anti-cancer therapeutics such as vaccines, PDL1 inhibitors, antiandrogen drugs, and chemotherapy agents. Several initial results have suggested that combination strategies are useful to increase the activity in mCRPC, even if the toxicity of the treatment can increase. The activity of combined treatments is still not predictable, but considering the ongoing studies, we believe that they have good potential that will lead to the discovery of an optimal therapeutic strategy.     

Stress hyperglycemia is predictive of worse outcome in patients with acute ischemic stroke undergoing intravenous thrombolysis

Journal of Thrombosis and Thrombolysis - No study investigated the possible detrimental effect of stress hyperglycemia on patients affected acute ischemic stroke (AIS) undergoing intravenous...     

When Genetic Load Does Not Correlate with Phenotypic Spectrum: Lessons from the GnRH Receptor (GNRHR)

Context: A broad spectrum of GnRH-deficient phenotypes has been identified in individuals with both mono- and biallelic GNRHR mutations. Objective: The objective of the study was to determine the correlation between the severity of the reproductive phenotype(s) and the number and functional severity of rare sequence variants in GNRHR. Subjects: Eight hundred sixty-three probands with different forms of GnRH deficiency, 46 family members and 422 controls were screened for GNRHR mutations. The 70 subjects (32 patients and 38 family members) harboring mutations were divided into four groups (G1-G4) based on the functional severity of the mutations (complete or partial loss of function) and the number of affected alleles (monoallelic or biallelic) with mutations, and these classes were mapped on their clinical phenotypes. Results: The prevalence of heterozygous rare sequence variants in GNRHR was significantly higher in probands vs. controls (P < 0.01). Among the G1-G3 groups (homozygous subjects with successively decreasing severity and number of mutations), the hypogonadotropic phenotype related to their genetic load. In contrast, subjects in G4, with only monoallelic mutations, demonstrated a greater diversity of clinical phenotypes. Conclusions: In patients with GnRH deficiency and biallelic mutations in GNRHR, genetic burden defined by severity and dose is associated with clinical phenotype. In contrast, for patients with monoallelic GNRHR mutations this correlation does not hold. Taken together, these data indicate that as-yet-unidentified genetic and/or environmental factors may combine with singly mutated GNRHR alleles to produce reproductive phenotypes.     

Reverse flow first dorsal metacarpal artery flap for covering the defect of distal thumb

Reconstruction of distal thumb injuries still remains a challenge for hand surgeons. Surgical treatment includes the use of local, regional, and free flaps. The purpose of this report is to present the results of the use of a sensitive reverse flow first dorsal metacarpal artery (FDMA) flap. The skin flap was designed on the radial side of the proximal phalanx of the index finger based on the ulnar and radial branch of the FDMA and a sensory branch of the superficial radial nerve. This neurovascular flap was used in five patients to cover distal soft‐tissue thumb defects. All flaps achieved primary healing except for one patient in whom superficial partial necrosis of the flap occurred, and the defect healed by second intention. All patients maintained the thumb original length and were able to return to their previous daily activities. The reverse flow FDMA flap is a reliable option to cover immediate and delayed defects of distal thumb, offering acceptable functional and cosmetic outcomes in respect to sensibility, durability, and skin‐match. © 2013 Wiley Periodicals, Inc. Microsurgery 34:283–286, 2014.