A historical review of experimental imaging of the beating heart coronary microcirculation in vivo

Following a myocardial infarction (MI), the prognosis of patients is highly dependent upon the re-establishment of perfusion not only in the occluded coronary artery, but also within the coronary microcirculation. However, our fundamental understanding of the pathophysiology of the tiniest blood vessels of the heart is limited primarily because no current clinical imaging tools can directly visualise them. Moreover, in vivo experimental studies of the beating heart using intravital imaging have also been hampered due to obvious difficulties related to significant inherent contractile motion, movement of the heart brought about by nearby lungs and its location in an anatomically challenging position for microscopy. However, recent advances in microscopy techniques, and the development of fluorescent reporter mice and fluorescently conjugated antibodies allowing visualisation of vascular structures, thromboinflammatory cells and blood flow, have allowed us to overcome some of these challenges and increase our basic understanding of cardiac microvascular pathophysiology. In this review, the elegant attempts of the pioneers in intravital imaging of the beating heart will be discussed, which focussed on providing new insights into the anatomy and physiology of the healthy heart microvessels. The reviews end with the more recent studies that focussed on disease pathology and increasing our understanding of myocardial thromboinflammatory cell recruitment and flow disturbances, particularly in the setting of diseases such as MI.     

Immunosuppression due to chronic ochratoxicosis in broiler chicks

Crystalline ochratoxin A (OA) was added to the feed of broiler chicks at 0.5 ppm and 2.0 ppm, and humoral and cell-mediated immunity (CMI) were studied. CMI was assessed by skin sensitivity testing, graft versus host (GVH) reaction and T lymphocyte count. Humoral immunity was examined by measuring the haemagglutinin (HA) response to sheep RBC (SRBC). In addition, total lymphocyte counts, total serum protein, albumin and globulin were determined and the phagocytic activity of splenic macrophages was measured in the nitroblue tetrazolium test (NBT). The weights of lymphoid organs were also recorded at post-mortem examination of the birds. Highly significant reductions in CMI were indicated by diminished skin sensitivity, GVH reactions and T lymphocyte counts. On the other hand, only the overall HA titres differed significantly between the various treatment groups. Total lymphocyte counts, total serum protein, serum albumin and serum globulin were significantly depressed on the 21st day of intoxication. The number of NBT-positive cells was drastically reduced in both the intoxicated groups compared with controls (P less than 0.05) and the weights of thymus, bursa of Fabricius and spleen of intoxicated birds were significantly reduced. The study illustrated the immunosuppressive effects of ochratoxicosis in broiler chicks.     

Receptor tyrosine kinase signaling in cancer radiotherapy and its targeting for tumor radiosensitization

Purpose: One of the most important implications of ‘Radiation Biology’ research is to improve cancer radiotherapy with minimum side effects. In this regard, combination of chemotherapy with radiation has significantly improved tumor control as well as overall survival in a variety of cancers. However, this has been achieved at the cost of significant normal tissue toxicity, due to the lack of specificity of chemotherapy. Membrane-localized receptor tyrosine kinases (RTKs) have been found to play a driving role in various hallmarks of cancer. Moreover, an early successful clinical trial using RTK-antagonist (cetuximab) to improve tumor radiosensitivity has led to an advancement in this field of research. However, a comprehensive review integrating these findings of various oncogenic RTKs, from basic radiobiology-to-radiotherapy clinical trials, is lacking in literature. Therefore, the present review analyses relevant in-vitro, in-vivo, preclinical/clinical studies and postulates the concept of ‘Radiation Biology of RTKs in Cancer’.

Conclusions: The present review elucidates the effect of IR on various oncogenic RTKs and their mechanisms, downstream signaling, intracellular translocations, their role in the repair of radiation-induced DNA damage and post-irradiation survival. Based on the knowledge derived from RTK biology and the analysis of relevant clinical trials, this review attempts to identify radiobiological considerations, which could be implemented in future trials, combining radiotherapy with RTK-antagonist. Additionally, we identify the radiosensitizing potential of recently developed RTK-targeted nanoformulations. This review would probably change the Radiation Oncologist’s view for translation of tumor-specific radiosensitization in clinic.     

A Prospective Randomized Study Comparing Maternal and Fetal Effects of Forceps Delivery and Vacuum Extraction

Objective

To compare maternal and neonatal effects of assisted vaginal delivery by forceps and vacuum extraction.

Methods

A prospective randomized study. One hundred eligible women requiring assisted vaginal delivery in the second stage of labor were randomized to deliver by forceps or vacuum extraction.

Results

All of those allocated to forceps delivery actually delivered with the allocated instrument (100 % delivery rate in forceps vs. 90 % in VE); however, maternal trauma (40 % in forceps vs. 10 % in VE, p < 0.001), use of analgesia (p < 0.001), and blood loss at delivery (234 ml in VE vs. 337 ml in forceps group, p < 0.05) were significantly less in the group allocated to deliver by vacuum extraction. Vacuum extraction, however, appears to predispose to an increase in neonatal jaundice and incidence of cephalhematoma. More serious neonatal morbidity was rare in both groups.

Conclusion

Extrapolation of the data from the study reveals that there is a significant reduction in maternal injuries. However, vacuum extraction has the potential to injure babies more.     

Pentafecta: a new concept for reporting outcomes of robot-assisted laparoscopic radical prostatectomy

Background

Widespread use of prostate-specific antigen screening has resulted in younger and healthier men being diagnosed with prostate cancer. Their demands and expectations of surgical intervention are much higher and cannot be adequately addressed with the classic trifecta outcome measures.

Objective

A new and more comprehensive method for reporting outcomes after radical prostatectomy, the pentafecta, is proposed.

Design, setting, and participants

From January 2008 through September 2009, details of 1111 consecutive patients who underwent robot-assisted radical prostatectomy performed by a single surgeon were retrospectively analyzed. Of 626 potent men, 332 who underwent bilateral nerve sparing and who had 1 yr of follow-up were included in the study group.

Measurements

In addition to the traditional trifecta outcomes, two perioperative variables were included in the pentafecta: no postoperative complications and negative surgical margins. Patients who attained the trifecta and concurrently the two additional outcomes were considered as having achieved the pentafecta. A logistic regression model was created to evaluate independent factors for achieving the pentafecta.

Results and limitations

Continence, potency, biochemical recurrence–free survival, and trifecta rates at 12 mo were 96.4%, 89.8%, 96.4%, and 83.1%, respectively. With regard to the perioperative outcomes, 93.4% had no postoperative complication and 90.7% had negative surgical margins. The pentafecta rate at 12 mo was 70.8%. On multivariable analysis, patient age (p = 0.001) was confirmed as the only factor independently associated with the pentafecta.

Conclusions

A more comprehensive approach for reporting prostate surgery outcomes, the pentafecta, is being proposed. We believe that pentafecta outcomes more accurately represent patients’ expectations after minimally invasive surgery for prostate cancer. This approach may be beneficial and may be used when counseling patients with clinically localized disease.     

Bilateral Traumatic Intracranial Hematomas and its Outcome: a Retrospective Study

The objective of this study was to evaluate the age distribution, mode of injury, type of hematomas, and their surgical outcome in patients with bilateral traumatic head injuries. The present study included 669 cases of traumatic head injury who presented at the neurosurgery emergency out of which 94 cases had bilateral head injuries from the period of August 2009 to April 2014. The data from the hospital computerized database were retrospectively analysed. Cases of bilateral traumatic head injury included 94 patients out of which 88.29 % (n?=?83) were males and 11.70 % (n?=?11) were females. Commonest mode of injury was road traffic accident in 56.38 % (n?=?53) followed by fall from height in 29.78 % (n?=?28). In our study, 25.53 % patients had epidural hematoma (EDH) with intracerebral hematoma (ICH) or contusion (n?=?24), followed by EDH with subarachnoid hemorrhage (SAH) in 18.08 % (n?=?17). At the time of discharge, all those patients managed conservatively had good Glasgow outcome scale (GOS) while with surgical intervention 58 % patients had good GOS, 19 % had moderate disability, and 9 % remained with severe disability. In cases of bilateral hematomas, EDH is most common and should be managed in neurosurgical emergency. Other combinations of bilateral intracranial hematomas should be managed according to the surgical indication and serial CT imaging.