Bilateral Whole Lung Lavage in Hereditary Pulmonary Alveolar Proteinosis in a 4-year-old Child Using Extracorporeal Membrane Oxygenation.

The hereditary form of pulmonary alveolar proteinosis (PAP) is an uncommon entity. We report a case of PAP due to colony-stimulating factor 2 receptor alpha (CSF2RA) gene mutation. The standard of care includes whole lung lavage (WLL). We faced two challenges: Firstly, a severely hypoxemic patient, and secondly, the nonavailability of appropriate size of double-lumen endotracheal tube for pediatric patients for a WLL while permitting single-lung ventilation. Hence, we performed WLL using venovenous extracorporeal membrane oxygenation (VV ECMO) with a successful outcome. The patient has been discharged and is off oxygen support since more than a year. There are only a few case reports of children having hereditary PAP treated with WLL using ECMO in Indian and Western literature. HOW TO CITE THIS ARTICLE: Prabhudesai P, Khosla I, Kulkarni S, Arya MK, Pandey A, Yadav N. Bilateral Whole Lung Lavage in Hereditary Pulmonary Alveolar Proteinosis in a 4-year-old Child Using Extra corporeal Membrane Oxygenation. Indian J Crit Care Med 2021;25(9):1069-1072.

Leprosy drug clofazimine activates peroxisome proliferator-activated receptor-γ and synergizes with imatinib to inhibit chronic myeloid leukemia cells.

Leukemia stem cells contribute to drug-resistance and relapse in chronic myeloid leukemia (CML) and BCR-ABL1 inhibitor monotherapy fails to eliminate these cells, thereby necessitating alternate therapeutic strategies for patients CML. The peroxisome proliferator-activated receptor-γ (PPARγ) agonist pioglitazone downregulates signal transducer and activator of transcription 5 (STAT5) and in combination with imatinib induces complete molecular response in imatinib-refractory patients by eroding leukemia stem cells. Thiazolidinediones such as pioglitazone are, however, associated with severe side effects. To identify alternate therapeutic strategies for CML we screened Food and Drug Administration-approved drugs in K562 cells and identified the leprosy drug clofazimine as an inhibitor of viability of these cells. Here we show that clofazimine induced apoptosis of blood mononuclear cells derived from patients with CML, with a particularly robust effect in imatinib-resistant cells. Clofazimine also induced apoptosis of CD34+38- progenitors and quiescent CD34+ cells from CML patients but not of hematopoietic progenitor cells from healthy donors. Mechanistic evaluation revealed that clofazimine, via physical interaction with PPARγ, induced nuclear factor kB-p65 proteasomal degradation, which led to sequential myeloblastoma oncoprotein and peroxiredoxin 1 downregulation and concomitant induction of reactive oxygen species-mediated apoptosis. Clofazimine also suppressed STAT5 expression and consequently downregulated stem cell maintenance factors hypoxia-inducible factor-1α and -2α and Cbp/P300 interacting transactivator with Glu/Asp-rich carboxy-terminal domain 2 (CITED2). Combining imatinib with clofazimine caused a far superior synergy than that with pioglitazone, with clofazimine reducing the half maximal inhibitory concentration (IC50) of imatinib by >4 logs and remarkably eroding quiescent CD34+ cells. In a K562 xenograft study clofazimine and imatinib co-treatment showed more robust efficacy than the individual treatments. We propose clinical evaluation of clofazimine in imatinib-refractory CML.

Assessment of Different Indices as Predictors of Difficult Airway in Obese Patients.

Introduction Difficulties with tracheal intubation contribute to the morbidity and mortality associated with anesthesia. Suggested predictors for difficult airway include, history of obstructive sleep apnea, high Mallampati score, elderly, male, short neck, and high Wilson score. However, none of these has high diagnostic accuracy particularly in obese population. Parameters used to quantify obesity such as Body Mass Index(BMI), mid arm circumference, skin fold thickness, etc. have not been used as independent predictors of difficult airway. This study has been designed to evaluate the accuracy of commonly used tools to assess difficult airway and to test other obesity markers as scale for assessing difficult airway i.e. Bag mask ventilation grade ≥3 or Cormack-Lehane Grade≥3 on Direct Laryngoscopy or number of intubation attempts ≥3. Aim To assess BMI, Mallampati grading, Neck circumference and Thyromental distance as predictors of difficult airway in obese patients and to validate neck circumference to thyromental distance ratio and skin fold thickness as a tool for assessment of difficult airway (Bag mask ventilation grade ≥3 or Cormack-Lehane Grade≥3 on Direct Laryngoscopy or number of intubation attempts ≥3.) in obese patients. Methods This prospective observational study was carried out on 51 obese patients (as per BMI) of ASA grade II, either sex, aged 23 to 57 years posted for elective surgery under general anesthesia with endotracheal intubation. After subjective assessment of difficult airway following data sets and variables were obtained - sex, weight, height, body mass index (BMI), Modified Mallampati class (MPG), Cormack-Lehane (CL) grade, adequacy of bag mask ventilation (BMV), number of endotracheal intubation attempts, patient's neck circumference (NC), thyromental distance (TMD), waist-hip ratio (WHR) and Skin fold thickness. The observations made during the study were statistically analyzed and correlated as predictors for difficult airway. Result Correlation of MPG to CL-grade (r-0.41, p-0.003), BMV (r-0.31, p-0.028) & No. of intubation attempts (r-0.37, p-0.007) was mild & statistically significant. Correlation of Neck Circumference with CL-grade (r-0.57, p-0.000), & No. of intubation attempts (r-0.62, p-0.000), found moderate & statistically significant, & with BMV was mild and statistically significant (r-0.48, p-0.000). Correlation of Thyromental Distance to CL-grade (r-0.65, p-0.000), BMV (r-0.70, p-0.000) & No. of intubation attempts (r-0.61, p-0.000) was moderate & statistically significant. Correlation of BMI to CL-grade (r-0.11, p-0.428), BMV (r-0.04, p-0.757) & No. of intubation attempts (r-0.16, p-0.257) was weak & not significant. Skin Fold Thickness showed no significant association with Difficult airway i.e., CL Grade (p-0.478), BMV (p-0.101), and No. of intubation attempts (p-0.143). Correlation of NC/TMD ratio with BMV (r-0.74, p-0.000), CL-grade (r-0.76, p-0.000), & No. of intubation attempts (r-0.77, p-0.000) was moderate & statistically significant. Conclusion NC, TMD and NC/TMD Ratio depicted a close association with airway difficulty in obese patients. Obesity grade is a risk factor for difficult airway but predictors of obesity including Skin Fold Thickness, individually did not show association with difficult airway (small sample size may be a limiting factor). None of the commonly performed tests alone has proven to be adequate in predicting difficult intubation in the obese population.

Hyperhomocysteinemia and low vitamin B12 are associated with the risk of early pregnancy loss: A clinical study and meta-analyses.

One-carbon metabolism is crucial for the maintenance of healthy pregnancy and alterations in this pathway have been associated with various pregnancy-related complications. Therefore, the present study was conducted to test the hypothesis that the altered folic acid, vitamin B12 and homocysteine levels are associated with the risk of early pregnancy loss (EPL). Plasma folic acid, vitamin B12 and homocysteine levels were analyzed in 83 females with EPL and 70 healthy pregnant females in their first trimester. Further, meta-analyses of folic acid, vitamin B12 and homocysteine were also performed involving various eligible studies. Results from our case-control study and meta-analysis showed that folic acid deficiency is not associated with the risk of EPL. On the other hand, low vitamin B12 and hyperhomocysteinemia were individually found to be significant risk factors for EPL in the present study (P < .01, P < .05, respectively) and meta-analysis as well (P < .001, P < .05, respectively). Vitamin B12 deficiency in combination with hyperhomocysteinemia was a more serious risk factor for EPL (Odds Ratio = 4.98, P = 0.002). Therefore, we conclude that vitamin B12 deficiency and elevated homocysteine levels are independent risk factors for EPL, and of higher risk when combined. The assessment of vitamin B12 and homocysteine levels may serve as a good screening marker for EPL risk.

Osteoblast studied on gelatin based biomaterials in rabbit Bone Bioengineering.

The bone-derived-osteoblast seeded biomaterials scaffold in tissue engineering, have displayed prominence in the treatment of the osseous medical condition. In vitro osteogenesis of rabbit osteoblast cell (rOb) from bone tissue (rT) and MSC-derived rOb from bone marrow (rM) on Gelatin-Hydroxyapatite (HG) based biomaterials was investigated. In this work, lyophilized biomaterial was prepared by the addition of amorphous chitosan ('C') to 'H' dispersed in 'G' matrix, to find its role in biomaterials biocompatibility. Isolated rOb seeded biomaterials were studied using CLSM and flow cytometry for proliferation potential. The biomaterial's core and surface morphology was studied from SEM-EDX and AFM respectively. Upon co-culture with HCG, rT over rM showed rabbit bone extracellular matrix (ECM) mimicking properties both in in vitro studies and biomaterials micro architecture. The in vitro metabolic behaviour was studied by Alamar Blue (AB) assay, DNA content using Hoechst 33258, potency via the activity of Alkaline Phosphatase (ALP), Calcium's relative content by Alizarin Red S (ARS) assay. A novel combination of biomaterials-cell interaction was observed when rT was co-cultured with HCG and proved effective in osteogenesis with regard to Bone Bioengineering.

In vitro studies on gelatin/hydroxyapatite composite modified with osteoblast for bone bioengineering.

A promising route towards bone tissue engineering is made by the raw materials of the composite which mimics properties of the extracellular matrix components. Herein, the favourable human origin bone cells were seeded on the scaffold types to investigate the best co-culture system. The same has been achieved after the synthesis and characterization of gelatin/hydroxyapatite composites infused with chitosan for their calcium to phosphate (Ca/P) ratio by SEM-EDX. Also, in vitro biodegradation and bio-mineralization determined after immersing in lysozyme and SBF respectively. Uni-axial Compressive Strength (UCS), porosity, qualitative to quantitative phase development by XRD and FTIR were evaluated. The human bone cell-seeded composite was tested by flow cytometry, CLSM, SEM and DSC. This study statistically signified the human mesenchymal stem cell (hM) derived bone cell as potential raw material for minor to severe bone related tissue regenerative studies.

The National Rural Health Mission in India: its impact on maternal, neonatal, and infant mortality.

The National Rural Health Mission (NRHM) has been a watershed in the history of India's health sector. As a previously unattempted investment, governance, and mobilization effort, the NRHM succeeded in injecting new energy into India's public health system. A huge expansion of infrastructure and human resources is the hallmark of the NRHM action. Demand-side initiatives led to enhanced utilization of public health facilities, especially for facility births. The impact is visible. The Mission has brought Millennium Development Goals 4 and 5 within India's grasp. Acceleration in infant and neonatal mortality reduction is especially notable. The NRHM has created conditions for the country to move toward universal health coverage.