Neuroparacoccidioidomycosis.

Paracoccidioidomycosis (PCM) is caused by a dimorphic fungus Paracoccidioides Brasiliensis and is endemic to subtropical areas of Central and South America. CNS involvement of PCM is extremely variable. NeuroPCM is found in 9.65% to 27.18% of PCM cases .Most neuro PCM patients presents with simultaneous involvement of other organ but isolated or initial CNS involvement may be a feature in 21%. Here we report a case of CNS PCM and this appears to be first reported case of PCM and CNS PCM in India.

Case of Suspected SARS-CoV-2 Vaccine-induced Immune Thrombotic Thrombocytopenia: Dilemma for Organ Donation.

Several vaccines were developed and rolled out at an unprecedented rate in response to the coronavirus disease-2019 (COVID-19) pandemic. Most vaccines approved globally by WHO for emergency use to combat the pandemic were deemed remarkably effective and safe. Despite the safety, rare incidences of vaccine-induced thrombosis and thrombocytopenia (VITT), sometimes known as vaccine-induced prothrombotic thrombocytopenia (VIPIT), have been reported. We report a case of young female with prothrombotic conditions and suspected VITT who developed catastrophic cerebral venous sinus thrombosis (CVST) and progressed to brain death. We highlight hurdles of organ retrieval from a brain-dead patient with suspected SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia. There is limited data and lack of substantial evidence regarding transplantation of organs from brain-dead patients with suspected VITT. How to cite this article: Tiwari AM, Zirpe KG, Gurav SK, Bhirud LB, Suryawanshi RS, Kulkarni SS. Case of Suspected SARS-CoV-2 Vaccine-induced Immune Thrombotic Thrombocytopenia: Dilemma for Organ Donation. Indian J Crit Care Med 2022;26(4):514-517.

Experiences from Garbha-Swasthya helpline.

Garbha-Swasthya helpline is a telephone helpline run by a tertiary care private hospital to address issues related to pregnancy and its complications. A review of the helpline data from September 2010 to December 2012 was conducted to study caller characteristics, number of calls and related information, and the reasons to call. Out of the total 696 voice calls, 421 were new callers and 275 were repeat callers and they comprised mainly pregnant women (73.3%), their relatives (24.8%), and medical professionals (1.9%). Most calls were related to first pregnancy and were mainly from Pune and other cities of Maharashtra. All calls by the medical professionals were regarding drug safety in pregnancy. The commonest category of questions (27.4%) was about exposures (drugs, alcohol, eclipse, radiation, etc.) and preexisting medical illness followed by pregnancy complications (18.5%), common medical issues such as nausea/vomiting during pregnancy, and delivery and postpartum period (14% each). Although the total number of calls received has steadily increased, efforts to create public and professional awareness to increase the usage of this helpline are warranted.

Gamma tocotrienol, a potent radioprotector, preferentially upregulates expression of anti-apoptotic genes to promote intestinal cell survival.

Gamma tocotrienol (GT3) has been reported as a potent ameliorator of radiation-induced gastrointestinal (GI) toxicity when administered prophylactically. This study aimed to evaluate the role of GT3 mediated pro- and anti-apoptotic gene regulation in protecting mice from radiation-induced GI damage. Male 10- to 12-weeks-old CD2F1 mice were administered with a single dose of 200 mg/kg of GT3 or equal volume of vehicle (5% Tween-80) 24 h before exposure to 11 Gy of whole-body γ-radiation. Mouse jejunum was surgically removed 4 and 24h after radiation exposure, and was used for PCR array, histology, immunohistochemistry, and immunoblot analysis. Results were compared among vehicle pre-treated no radiation, vehicle pre-treated irradiated, and GT3 pre-treated irradiated groups. GT3 pretreated irradiated groups, both 4h and 24h after radiation, showed greater upregulation of anti-apoptotic gene expression than vehicle pretreated irradiated groups. TUNEL staining and intestinal crypt analysis showed protection of jejunum after GT3 pre-treatment and immunoblot results were supportive of PCR data. Our study demonstrated that GT3-mediated protection of intestinal cells from a GI-toxic dose of radiation occurred via upregulation of antiapoptotic and downregulation of pro-apoptotic factors, both at the transcript as well as at the protein levels.

Mobilization of progenitor cells into peripheral blood by gamma-tocotrienol: a promising radiation countermeasure.

Gamma-tocotrienol (GT3), a vitamin E isoform, is shown to induce high levels of granulocyte colony stimulating factor (G-CSF) in mice. G-CSF is a key cytokine used for stimulation of hematopoiesis, and mobilization of hematopoietic stem and progenitor cells into peripheral blood. GT3 is also shown to induce vascular endothelial growth factor (VEGF), another important cytokine necessary for vasculogenesis and endothelial progenitor mobilization. Since GT3 induces both these cytokines, we tested whether GT3 mobilizes hematopoietic and endothelial progenitors in mice. GT3 (200mg/kg) was injected in 10-week-old CD2F1 mice and mobilization of progenitors in peripheral blood was analyzed at 24, 48, and 72 h post-administration. Circulating hematopoietic progenitor cells (HPCs, Lin(-), cKit(+)), endothelial progenitor cells (EPCs, Lin(-), CD34(+), Flk(+)), and stromal progenitor cells (SPCs, Lin(-), CD29(+), CD105(+)) in peripheral blood mononuclear cells (PBMCs) were analyzed simultaneously by flow cytometry. Mobilized HPCs, EPCs and SPCs in PBMC were also measured by colony-forming unit (CFU) assay in progenitor-specific media. Three groups of mice received vehicle, GT3 and GT3 plus AMD3100, a receptor antagonist used to enhance mobilization. GT3 induced significant mobilization of all three progenitor cell types compared to vehicle in peripheral blood; AMD3100 enhanced GT3-induced mobilization even further. Mobilization of progenitor cells in peripheral blood by GT3 indicates that GT3 can be used as an alternative to G-CSF and VGEF to mobilize HPCs and EPCs.

Gamma-tocotrienol, a radiation prophylaxis agent, induces high levels of granulocyte colony-stimulating factor.

Gamma-tocotrienol (GT3), a promising radioprotectant, is shown to protect CD2F1 mice from radiation-induced neutropenia and thrombocytopenia when given 24h prior to total-body irradiation. GT3 also is shown to increase white blood cells (WBC) and absolute neutrophil counts (ANC) transiently in peripheral blood. We hypothesized that increases in WBC and ANC may involve stimulation of hematopoiesis possibly by cytokines and growth factors. To evaluate the effects of GT3 on hematopoietic system, we measured various cytokines, chemokines and growth factors by cytokine array and Bio-Plex assays. Both showed strong induction of various cytokines and chemokines. GT3 treatment resulted in significant increases in G-CSF, IL-1α, IL-1ß, IL-6, IL-12p70, IL-17, MIP-1α, and KC levels. G-CSF levels increased markedly within 12-24h after administration (5441 pg/ml in GT3-treated groups compared to 17 pg/ml in vehicle control). Most of these cytokine levels were elevated in the presence or absence of radiation. Time-course analysis of G-CSF and IL-6 induction showed that both cytokines were induced transiently after GT3 administration, and returned to normal levels by 48 h post-administration. For G-CSF, the peak was observed between 12 and 24h post-administration of GT3; however, the highest levels of IL-6 were obtained between 6 and 12h. These results demonstrate that GT3 induced high levels of G-CSF and other inflammatory cytokines and chemokines within 24h after administration. Survival studies reported showed that the most efficacious time for administering GT3 was 24h prior to irradiation, possibly because it induced key hematopoietic cytokines in that time window. These results also suggest a possible role of GT3-induced G-CSF stimulation in protecting mice from radiation-induced neutropenia and thrombocytopenia.