Hedgehog (Hh) signaling pathway is a valid therapeutic target in a wide range of malignancies. We focus here on glioblastoma multiforme (GBM), a lethal malignancy of the central nervous system (CNS). By analyzing RNA-sequencing based transcriptomics data on 149 clinical cases of TCGA-GBM database we show here a strong correlation (r = 0.7) between GLI1 and PTCH1 mRNA expression—as a hallmark of the canonical Hh-pathway activity in this malignancy. GLI1 mRNA expression varied in 3 orders of magnitude among the GBM patients of the same cohort showing a single continuous distribution—unlike the discrete high/low-GLI1 mRNA expressing clusters of medulloblastoma (MB). When compared with MB as a reference, the median GLI1 mRNA expression in GBM appeared 14.8 fold lower than that of the “high-Hh” cluster of MB but 5.6 fold higher than that of the “low-Hh” cluster of MB. Next, we demonstrated statistically significant up- and down-regulation of GLI1 mRNA expressions in GBM patient-derived low-passage neurospheres in vitro by sonic hedgehog ligand-enriched conditioned media (shh-CM) and by Hh-inhibitor drug vismodegib respectively. We also showed clinically achievable dose (50 μM) of vismodegib alone to be sufficient to induce apoptosis and cell cycle arrest in these low-passage GBM neurospheres in vitro. Vismodegib showed an effect on the neurospheres, both by down-regulating GLI1 mRNA expression and by inducing apoptosis/cell cycle arrest, irrespective of their relative endogenous levels of GLI1 mRNA expression. We conclude from our study that this single continuous distribution pattern of GLI1 mRNA expression technically puts almost all GBM patients in a single group rather than discrete high- or low-clusters in terms of Hh-pathway activity. That is suggestive of therapies with Hh-pathway inhibitor drugs in this malignancy without a need for further stratification of patients on the basis of relative levels of Hh-pathway activity among them.

Premise and Objective:Elective laparoscopic cholecystectomy (LC) has low risk for post-operative infectious complications; still most clinicians use persistent post-operative prophylactic antibiotics out of habit, tradition, or simply as defensive practice due to evolving medicolegal implications of a large number of surgeries being showcased as daycare or next day discharge procedures. This randomised prospective trial was done to test the need for such prophylaxis in cases of elective LC in a rural/semi-urban setting.Materials and Methods:Two hundred and ten successive patients undergoing elective LC were randomised into groups receiving single dose of injection ceftriaxone at the time of induction of anaesthesia, (Group A = 112 cases) and those who in addition to above received injection ceftriaxone twice daily for 2 days postoperatively (Group B = 98 cases). Post-operative infectious complications between two groups were compared for variables such as age, sex, body mass index and bile/stone spillage.Results:There was no significant difference in surgical site infection rates between the groups for variables such as age, sex, body mass index, duration of symptoms, American Society of Anesthesiologists grade, duration of surgery and hospital stay. Intraoperative spillage of stones (9.8% [A]: 5.1% [B]) did not increase infectious complications even in the presence of positive bile culture (Group A, N = 7 vs. Group B, N = 3). An operative time of greater than 60 min was found to be associated with increased surgical site infection (P = 0. 0006).Conclusion:Single dose of ceftriaxone at the time of induction is adequate prophylaxis following elective LC even in the rural/semi-urban Indian setting and routine continued administration of antibiotic should be abandoned as it contributes to adverse reactions, drug resistance and unnecessary financial burden.

Contrecoup injuries comprise a group of focal brain injuries that occur at areas distant from the point of impact. It has been hypothesized that patients with contrecoup injuries would have a worse outcome because of the diffuse nature of injury. At Nilratan Sircar Medical College, Kolkata, 74 patients presenting with contrecoup injuries over a period of 1 year were prospectively analyzed. Site of primary impact was determined by clinical and CT scan criteria. The age, modes of injury, Glasgow coma scale (GCS), site of injury, pattern of injury, and mortality were analyzed. Delayed presentation of contrecoup injury in patients who deteriorated over time was also noted in imaging. The presence of contrecoup injury implies that the traumatic forces have dissipated into the brain, and from the biomechanisms explained, the brain is likely to have suffered greater damage than the case in coup injury alone. The present study shows that the presence of contrecoup contusions is associated with a poor prognosis across all GCS and age categories.

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Epidural hematoma (EDH) is a traumatic accumulation of blood between the inner table of the skull and the dural membrane. Contact-related skull deformation causes inbending or fracturing of cranium or both, leading to separation of the dura mater from inner table. This injures the dural arteries, veins, venous sinus, or diploid channels, producing EDH. They usually occur as a result of direct impact injuries to the head, ipsilateral to impact side. Incidence of epidural hematoma is 1 to 3% of all head injuries. Contrecoup EDH cases are rare. and because of its rarity, we present a case report of a 17-year-old boy with contrecoup EDH who sustained head injury due to road traffic accident. Computed tomography of the brain showed left occipital bone fracture and large contrecoup extradural hematoma in right frontal region associated with pneumocephalus and hemorrhagic contusional edema beneath it. The EDH was operated on, and the patient was discharged uneventfully.