PRDM16 co-operates with LHX2 to shape the human brain.

PRDM16 is a dynamic transcriptional regulator of various stem cell niches, including adipocytic, hematopoietic, cardiac progenitors, and neural stem cells. PRDM16 has been suggested to contribute to 1p36 deletion syndrome, one of the most prevalent subtelomeric microdeletion syndromes. We report a patient with a de novo nonsense mutation in the PRDM16 coding sequence, accompanied by lissencephaly and microcephaly features. Human stem cells were genetically modified to mimic this mutation, generating cortical organoids that exhibited altered cell cycle dynamics. RNA sequencing of cortical organoids at day 32 unveiled changes in cell adhesion and WNT-signaling pathways. ChIP-seq of PRDM16 identified binding sites in postmortem human fetal cortex, indicating the conservation of PRDM16 binding to developmental genes in mice and humans, potentially at enhancer sites. A shared motif between PRDM16 and LHX2 was identified and further examined through comparison with LHX2 ChIP-seq data from mice. These results suggested a collaborative partnership between PRDM16 and LHX2 in regulating a common set of genes and pathways in cortical radial glia cells, possibly via their synergistic involvement in cortical development.

Post-cardiac Surgery Delirium: When the Details Matter!

How to cite this article: Suresh V, Magoon R. Post-cardiac Surgery Delirium: When the Details Matter! Indian J Crit Care Med 2024;28(2):185-187.

PRDM16 co-operates with LHX2 to shape the human brain.

PRDM16 is a dynamic transcriptional regulator of various stem cell niches, including adipocytic, hematopoietic, cardiac progenitors, and neural stem cells. PRDM16 has been suggested to contribute to 1p36 deletion syndrome, one of the most prevalent subtelomeric microdeletion syndromes. We report a patient with a de novo nonsense mutation in the PRDM16 coding sequence, accompanied by lissencephaly and microcephaly features. Human stem cells were genetically modified to mimic this mutation, generating cortical organoids that exhibited altered cell cycle dynamics. RNA sequencing of cortical organoids at day 32 unveiled changes in cell adhesion and WNT-signaling pathways. ChIP-seq of PRDM16 identified binding sites in postmortem human fetal cortex, indicating the conservation of PRDM16 binding to developmental genes in mice and humans, potentially at enhancer sites. A shared motif between PRDM16 and LHX2 was identified and further examined through comparison with LHX2 ChIP-seq data from mice. These results suggested a collaborative partnership between PRDM16 and LHX2 in regulating a common set of genes and pathways in cortical radial glia cells, possibly via their synergistic involvement in cortical development.

Perioperative Variation in Optic Nerve Sheath Diameter - A Prospective Observational Study of Traumatic Brain Injury Patients Undergoing Decompressive Craniectomy.

Background: Measuring optic nerve sheath diameter (ONSD) by transbulbar ultrasonography (TBUS) can suffice non-invasive ICP measurement with considerable accuracy. Objective: The primary objective of this study was to evaluate the perioperative variation in ONSD by TBUS in Traumatic Brain Injury (TBI) patients undergoing emergency craniectomy. Methods: We prospectively compared bilateral ONSD measurements in 45 consecutive TBI cases undergoing decompressive craniectomy under general anesthesia; before and after surgery. A total of 180 ONSD images were obtained and measurements were done by the same investigator blinded to the pre/postoperative nature of the image. Results: Based on preoperative Glasgow Coma Scores, 34 cases (75.5%) had severe TBI; 10 cases (22.2%) moderate TBI; and 1 case (2.2%) mild TBI. Preoperative ONSD in the study population were as 6.625 ± 0.414mm. Average ONSD reduced significantly by 0.249 ± 0.148 mm (P < 0.001) after craniectomy. On pooled analysis of cases undergoing right versus left sided craniectomy average ONSD reduced significantly by 0.252 ± 0.173 mm (P < 0.001) and 0.259 ± 0.139 mm (P < 0.001), respectively. ONSD of right eye with left eye and vice-versa were strongly correlated both pre/postoperatively with Pearson correlation coefficients (r)=0.879 (P < 0.001) and r = 0.827 (P < 0.001), respectively. Conclusions: In TBI cases undergoing decompressive craniectomy ONSD is bilaterally increased preoperatively. ONSD reduces significantly immediately after craniectomy; however, the diameters did not near the normal range. There hold a strong correlation between right/left ONSD measurements irrespective of the laterality of injury or side of surgery. Variable elastic properties of ONS in an injured brain can possibly explain our findings.

Airborne Infections and Emergency Surgery: The COVID-19 Pandemic Perspective.

COVID-19 which emerged in Wuhan, China has rapidly spread all over the globe and the World Health Organisation has declared it a pandemic. COVID-19 disease severity shows variation depending on demographic characteristics like age, history of chronic illnesses such as cardio-vascular/renal/respiratory disease; pregnancy; immune-suppression; angiotensin converting enzyme inhibitor medication use; NSAID use etc but the pattern of disease spread is uniform - human to human through contact, droplets and fomites. Up to 3.5% of health care workers treating COVID-19 contact an infection themselves with 14.8% of these infections severe and 0.3% fatal. The situation has spread panic even among health care professionals and the cry for safe patient care practices are resonated world-wide. Surgeons, anesthesiologists and intensivists who very frequently perform endotracheal intubation, tracheostomy, non-invasive ventilation and manual ventilation before intubation are at a higher odds ratio of 6.6, 4.2, 3.1 and 2.8 respectively of contacting an infection themselves. Elective surgery is almost always deferred in fever/infection scenarios. A surgeon and an anesthesiologist can anytime encounter a situation where in a COVID-19 patient requires an emergency surgery. COVID-19 cases requiring surgery predispose anesthesiologists and surgeons to cross-infection threats. This paper discusses, the COVID-19 precautionary outlines which has to be followed in the operating room; personal protective strategies available at present; methods to raise psychological preparedness of medical professionals during a pandemic; conduct of anesthesia in COVID-19 cases/suspect cases; methods of decontamination after conducting a surgery for COVID-19 case in the operating room; and post-exposure prophylaxis for medical professionals.

Implementation and adherence to a speciality-specific checklist for neurosurgery and its influence on patient safety.

BACKGROUND AND AIMS: Neurosurgery involves a high level of expertise coupled with enduring and long duration of working hours. There is a paucity of published literature about the experience with a speciality-specific checklist in neurosurgery. We conducted a cross-sectional observational study to identify the adherence to various elements of the Modified World Health Organization Surgical Safety Checklist (WHO SSC) for neurosurgery by the operating room (OR) team. METHODS: We implemented an intra-operative Modified WHO SSC consisting of 40 tools for neurosurgery, in 200 consecutive elective cases. Trained anaesthesiologists assumed the role of checklist co-ordinator. The checklist divided the surgery into 5 phases, each corresponding to a specific time-period. The adherence rates to various tools were evaluated and areas where the checklist prompted a corrective measure were analysed. RESULTS: A total of 131 cases undergoing craniotomy and 69 cases undergoing spine surgery were studied. With the 40-point modified SSC applied in 200 cases, we analysed a total of 8000 observations. The modified checklist prompted the OR team to adhere to speciality-specific safety practices about application of compression stockings (9.5%); airway precautions in unstable cervical spine (2.5%); precautions for treatment of raised intracranial pressure (10.5%); and intraoperative neuro-monitoring (5%). CONCLUSION: The implementation of Modified WHO SSC for Neurosurgery, by a designated checklist co-ordinator, can rectify anaesthetic and surgical facets promptly, without increasing the OR time. The anaesthesiologist as SSC coordinator can effectively implement an intraoperative checklist ensuring excellent participation of operating room team members.

Fluid responsiveness to passive leg raising in patients with and without coronary artery disease: A prospective observational study.

Introduction: Hemodynamic stability and fluid responsiveness (FR) assume importance in perioperative management of patients undergoing major surgery. Passive leg raising (PLR) is validated in assessing FR in intensive care unit patients. Very few studies have examined FR to PLR in intraoperative scenario. We prospectively studied FR to PLR using transesophageal echocardiography (TEE), in patients with no coronary artery disease (CAD) undergoing major neurosurgery and those with CAD undergoing coronary artery bypass grafting (CABG). Methods: We enrolled 29 adult consenting patients undergoing major neurosurgery with TEE monitoring and 25 patients undergoing CABG. After induction of anesthesia, baseline hemodynamic parameters were obtained which was followed by PLR using automated adjustment of the operating table. Clinical and TEE-derived hemodynamic parameters were recorded at 1 and 10 min after PLR following which patients were returned to supine position. Results: A total of 162 TEE and clinical examinations were done across baseline, 1 and 10 min after PLR; and paired comparison was done at data intervals of baseline versus 1 min PLR, baseline versus 10 min PLR, and 1 min versus 10 min PLR. There was no significant change in hemodynamic variables at any of the paired comparison intervals in patients undergoing neurosurgery. CABG cases had significant hemodynamic improvement 1 min after PLR, partially sustained at 10 min. Conclusion: Patients undergoing CABG had significant hemodynamic response to PLR, whereas non-CAD patients undergoing neurosurgery did not. A blood pressure-left ventricular end-diastolic volume combination represented strong correlation in response prediction (Pearson's coefficient 0.641; P < 0.01).

Post-herpetic Neuralgia: A Systematic Review of Current Interventional Pain Management Strategies.

BACKGROUND: Post-herpetic neuralgia (PHN) is usually a constant or intermittent burning, stabbing, or sharp shooting pain with hyperalgesia or allodynia, persisting beyond the healing of herpetic skin lesions. This review was carried out in concordance to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. We used PICOS (Population, Intervention, Control, and Outcome Study) design for inclusion of potential studies into this review. Online literature available in PubMed, Cochrane, and Embase was searched for studies from January 1995 till March 2020, which evaluated interventional treatments in PHN by an independent reviewer, using the relevant medical subject heading (MeSH) terms. We analyzed the following outcome parameters with regard to each intervention-pain status at predefined fixed intervals after the intervention, quality of sleep using any of the reported questionnaires, analgesic consumption, functional evaluation, and quality of life assessment after the intervention. CONCLUSION: Interventional pain management options provide effective and long-lasting pain relief to patients not responding to medical management. The choice of intervention will depend on the region involved, cost, and invasiveness. Simple procedures such as intercostal nerve blocks/neurolysis, stellate ganglion blocks, paravertebral neurolysis, epidural steroid injections, and dorsal root ganglion-radiofrequency ablation are effective interventions, and if they fail, spinal cord stimulators could be effective in the hands of experienced pain physicians.

An Algorithm Measuring Donor Cell-Free DNA in Plasma of Cellular and Solid Organ Transplant Recipients That Does Not Require Donor or Recipient Genotyping.

Cell-free DNA (cfDNA) has significant potential in the diagnosis and monitoring of clinical conditions. However, accurately and easily distinguishing the relative proportion of DNA molecules in a mixture derived from two different sources (i.e., donor and recipient tissues after transplantation) is challenging. In human cellular transplantation, there is currently no useable method to detect in vivo engraftment, and blood-based non-invasive tests for allograft rejection in solid organ transplantation are either non-specific or absent. Elevated levels of donor cfDNA have been shown to correlate with solid organ rejection, but complex methodology limits implementation of this promising biomarker. We describe a cost-effective method to quantify donor cfDNA in recipient plasma using a panel of high-frequency single nucleotide polymorphisms, next-generation (semiconductor) sequencing, and a novel mixture model algorithm. In vitro, our method accurately and rapidly determined donor:recipient DNA admixture. For in vivo testing, donor cfDNA was serially quantified in an infant with a urea cycle disorder after receiving six daily infusions of donor liver cells. Donor cfDNA isolated from 1 to 2 ml of recipient plasma was detected as late as 24 weeks after infusion suggesting engraftment. The percentage of circulating donor cfDNA was also assessed in pediatric and adult heart transplant recipients undergoing routine endomyocardial biopsy with levels observed to be stable over time and generally measuring <1% in cases without moderate or severe cellular rejection. Unlike existing non-invasive methods used to define the proportion of donor cfDNA in solid organ transplant patients, our assay does not require sex mismatch, donor genotyping, or whole-genome sequencing and potentially has broad application to detect cellular engraftment or allograft injury after transplantation.