Low versus standard dose intravenous alteplase in the treatment of acute ischemic stroke in Egyptian patients

Objectives:To assess low dose altepase outcome and safety in comparison with a standard-dose regimen for acute ischemic stroke treatment in Egyptian patients.Materials:An observational prospective cohort non-randomized single blinded study was carried out during the period from November 2017 to December 2018. Eighty Egyptian acute ischemic stroke patients, all eligible for intravenous alteplase, were subdivided into 2 groups (40 patients in each group). Patients were thrombolysed at a dose of 0.6 mg/kg in the first group and 0.9 mg/kg in the second group. Both groups were compared in regard to safety and outcome. Safety was expressed by the rate of symptomatic intracranial hemorrhage (SICH) and 3 months mortality, while outcome was expressed by favorable outcomes at three months (modified Rankin Scale [mRS] of 0 to 2).Results:In the first group, 69.2% (n=27) achieved favorable outcomes at 90 days compared with 64.1% (n=25) in the second group (p=0.631). Ninety-day mortality was 5% (n=2) in the first group versus 2.5% (n=1) in the second group (p=0.556). Symptomatic intracranial hemorrhage was noted in 3 patients in the second group and zero patients in the first group (p=0.077).Conclusion:Low-dose alteplase could be a practical alternative for Egyptian populations with acute ischemic stroke especially in 3 to 4.5 hours window.

Cerebrovascular stroke is the second death and the seventh disability leading cause worldwide.¹ Tissue-type plasminogen activator (tPA) alteplase was the first medication approved by the Food and Drug Administration (FDA) for the acute ischemic stroke (AIS) treatment on June 1996, within 3 hours of stroke onset with a recommended dose of 0.9 mg/kg (maximum 90mg).² In 2008, the safety of using alteplase within 3 to 4.5 hours of stroke onset was approved by the Safe Implementation of Treatments in Stroke International Stroke Thrombolysis Registry (SITS -ISTR)³ and the European Cooperative Acute Stroke Study (ECASS III).⁴ However, thrombolytic therapy use has not been widely adopted, especially in developing countries. The restricted time window (3 to 4.5 hours), intracerebral hemorrhage (ICH) risk and the drug high cost are major obstacles preventing its broad application.⁵ Coagulation and fibrinolysis responses differ among different races, which increase symptomatic intracerebral hemorrhage (SICH) risk with standard-dose alteplase⁶ in Asian populations, many Asian neurologists considered alteplase low dose to be a better alternative for ischemic stroke treatment. Many studies had been conducted in order to prove the efficacy and safety of Alteplase low dose.^7-9 One of these studies was the Japan Alteplase Clinical Trial (J-ACT) conducted by Yamaguchi et al¹⁰ According to this study, using a 0.6 mg/kg dose of intravenous recombinant tissue plasminogen activator (rtPA) in Japanese patients was safe and effective. Despite the relatively stroke high rate among Egyptian populations, 963/100,000 inhabitants, only less than 1% of stroke patients receive intravenous thrombolysis. A major reason for this is the drug cost.^11,12 Low-dose regimens (0.6 mg/kg) use will lower the economic burden of thrombolytic therapy in the community and will greatly promote the implementation of this therapy in Egypt. Our study aim was to assess the outcome and safety of alteplase low dose in comparison to the standard-dose regimen in AIS treatment in Egypt.     

Routine versus selective histologic analysis of gallbladder specimens for the detection of incidental gallbladder cancers. A retrospective review over 9 years of activity with a special focus on patients' age

Background

Incidental gallbladder cancer (IGC) is an infrequent possibility in patients undergoing cholecystectomies. Routine histologic examination of all gallbladder specimens is the current approach to detect this disease. Our study presents the influence of age to perform a selective histologic analysis.

Methods

A retrospective review was conducted of all gallbladder specimens during the last 9 years in our hospital. The medical notes were retrieved for cases of IGC or dysplasia and perioperative data were collected.

Results

A total of 3,330 cholecystectomies were conducted over the study period, 3,041 for gallstone disease. Twelve patients were found with dysplasia and 13 patients with IGC, all of them occurred in gallbladders removed for gallstone diseases. There were 18 men with a median age of 65 years (range 18 to 85). Median age for cancer patients was 70 years (range 51 to 85) and 54 years for dysplasia (range 18 to 75). No patient below the age of 51 years (n = 1,464) experienced IGCs.

Conclusion

Age should be considered as an additional factor for a selective approach to the histologic analysis of all gallbladder specimens following cholecystectomies.     

External validation of the Heidenreich criteria for patient selection for unilateral or bilateral retroperitoneal lymph node dissection for post-chemotherapy residual masses of testicular cancer

Objective

To validate the Heidenreich criteria for patient selection for unilateral retroperitoneal lymph node dissection (RPLND) for residual masses after chemotherapy for nonseminomatous germ cell tumor (NSGCT).

Subjects/patients and methods

For validation, the data of 59 patients who underwent RPLND for residual masses of NSGCT were used. Of these patients, 23 (39 %) qualified for a modified RPLND, the others had an indication for a bilateral dissection. Results from histopathology after RPLND and follow-up data for relapse inside or outside the zone of the resection template were considered for validation.

Results

In the study cohort, median age at time of RPLND was 31 years. The 2-year disease-free survival was 90 and 96 % for the bilateral and the unilateral RPLND patients, respectively. Overall, 8 (14 %) relapses were observed after a median follow-up of 54 month. Of these, 6 were outside of the resection field and 2 were in-field. Of the 23 patients with indication for a modified RPLND, 1 patient relapsed in the contralateral testis and 1 inside the modified RPLND template. No relapse was observed outside the modified RPLND field and inside the untouched contralateral RPLND field. The Heidenreich criteria did therefore not misclassify a single patient.

Conclusion

The Heidenreich criteria for the selection of candidates for unilateral RPLND for residual masses after chemotherapy allow a highly reliable selection of patients. The application of the Heidenreich criteria can help to reduce comorbidity and invasiveness of RPLND.     

Fibroblast growth factor 2 decreases bleomycin‐induced pulmonary fibrosis and inhibits fibroblast collagen production and myofibroblast differentiation

Fibroblast growth factor (FGF) signaling has been implicated in the pathogenesis of pulmonary fibrosis. Mice lacking FGF2 have increased mortality and impaired epithelial recovery after bleomycin exposure, supporting a protective or reparative function following lung injury. To determine whether FGF2 overexpression reduces bleomycin‐induced injury, we developed an inducible genetic system to express FGF2 in type II pneumocytes. Double‐transgenic (DTG) mice with doxycycline‐inducible overexpression of human FGF2 (SPC‐rtTA;TRE‐hFGF2) or single‐transgenic controls were administered intratracheal bleomycin and fed doxycycline chow, starting at either day 0 or day 7. In addition, wild‐type mice received intratracheal or intravenous recombinant FGF2, starting at the time of bleomycin treatment. Compared to controls, doxycycline‐induced DTG mice had decreased pulmonary fibrosis 21 days after bleomycin, as assessed by gene expression and histology. This beneficial effect was seen when FGF2 overexpression was induced at day 0 or day 7 after bleomycin. FGF2 overexpression did not alter epithelial gene expression, bronchoalveolar lavage cellularity or total protein. In vitro studies using primary mouse and human lung fibroblasts showed that FGF2 strongly inhibited baseline and TGFβ1‐induced expression of alpha smooth muscle actin (αSMA), collagen, and connective tissue growth factor. While FGF2 did not suppress phosphorylation of Smad2 or Smad‐dependent gene expression, FGF2 inhibited TGFβ1‐induced stress fiber formation and serum response factor‐dependent gene expression. FGF2 inhibition of stress fiber formation and αSMA requires FGF receptor 1 (FGFR1) and downstream MEK/ERK, but not AKT signaling. In summary, overexpression of FGF2 protects against bleomycin‐induced pulmonary fibrosis in vivo and reverses TGFβ1‐induced collagen and αSMA expression and stress fiber formation in lung fibroblasts in vitro, without affecting either inflammation or epithelial gene expression. Our results suggest that in the lung, FGF2 is antifibrotic in part through decreased collagen expression and fibroblast to myofibroblast differentiation. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Philtrum length and intercommissural distance measurements at mixed dentition period

Anthropometric measurements of the lip and mouth are of great importance in clinical dysmorphology as well as reconstructive plastic surgery. In this study, the philtrum length (PhL) and intercommissural distance (ICmD) nomograms for Egyptian children in the mixed dentition period were established. A group of 1,338 Egyptian students in primary schools (735 boys and 603 girls) were included in the study. The students were at mixed dentition period and their ages ranged from 7 to 12 years. Anthropometric norms of PhL and ICmD were developed with significant sex difference in certain groups. A ratio between PhL and ICmD was developed. These data will help facilitate both objective and subjective evaluation of the lip and mouth for proper diagnosis of orofacial anomalies and variations as well as for ideal treatment plans.     

Effects of preoperative long-term glycemic control on operative outcomes following pancreaticoduodenectomy

Background

Diabetes mellitus is postulated to be both a risk factor and manifestation of pancreatic adenocarcinoma. This study evaluated the effects of preoperative glycemic control as determined by hemoglobin A1c (HbA1c) on outcomes following pancreaticoduodenectomy (PD).

Methods

A prospective cohort study whereby HbA1c was assessed preoperatively in 243 patients undergoing PD was performed. The primary outcome measure was operative morbidity. Secondary outcomes included individual adverse events, time to dietary resumption, and length of stay.

Results

Preoperative HbA1c ranged from 4.0% to 13.5%. Overall morbidity and incidence of specific adverse events were similar regardless of preoperative HbA1c. No correlation between HbA1c and length of stay, dietary resumption, or readmission was observed. Pancreatic fistula formation had a decreased incidence in patients with elevated versus normal HbA1c (2.2% vs 9.6%, P = .083).

Conclusions

PD can be safely performed in patients with HbA1c levels suggestive of poor long-term preoperative glycemic control. Medical efforts to optimize HbA1c should not delay resection.     

The effect of interleukin-17F on vasculogenic mimicry in oral tongue squamous cell carcinoma

Oral tongue squamous cell carcinoma (OTSCC) is one of the most common cancers worldwide and is characterized by early metastasis and poor prognosis. Recently, we reported that extracellular interleukin-17F (IL-17F) correlates with better disease-specific survival in OTSCC patients and has promising anticancer effects in vitro. Vasculogenic mimicry (VM) is the formation of an alternative vasculogenic system by aggressive tumor cells, which is implicated in treatment failure and poor survival of cancer patients. We sought to confirm the formation of VM in OTSCC and to investigate the effect of IL-17F on VM formation. Here, we showed that highly invasive OTSCC cells (HSC-3 and SAS) form tube-like VM on Matrigel similar to those formed by human umbilical vein endothelial cells. Interestingly, the less invasive cells (SCC-25) did not form any VM structures. Droplet-digital PCR, FACS, and immunofluorescence staining revealed the presence of CD31 mRNA and protein in OTSCC cells. Additionally, in a mouse orthotopic model, HSC-3 cells expressed VE-cadherin (CD144) but lacked Von Willebrand Factor. We identified different patterns of VM structures in patient samples and in an orthotopic OTSCC mouse model. Similar to the effect produced by the antiangiogenic drug sorafenib, IL-17F inhibited the formation of VM structures in vitro by HSC-3 and reduced almost all VM-related parameters. In conclusion, our findings indicate the presence of VM in OTSCC and the antitumorigenic effect of IL-17F through its effect on the VM. Therefore, targeting IL-17F or its regulatory pathways may lead to promising therapeutic strategies in patients with OTSCC.