Solitary Periosteal Osteoma of the Mandible : A case report

Osteoma of the jaw bones is a rare entity with very few cases reported in the literature. Osteomas are benign, slow-growing osteogenic tumours of the bone commonly encountered in the craniofacial skeleton and characterised by the proliferation of compact or cancellous bone. They can be central, peripheral or extra-skeletal in their location. In the facial region, periosteal osteomas occur more frequently in the paranasal sinuses, but solitary periosteal osteomas of the jaw bones are quite rare. The mandible is more commonly affected than the maxilla, with the sites of predilection being the lingual aspect of the body, the angle and the inferior border. We report a case of a solitary periosteal osteoma on the buccal aspect of the mandible in a 42-year-old woman.

Foetal umbilical artery doppler versus NST as predictors of adverse perinatal outcome in severe preeclampsia and foetal growth restriction

Background: With the advent of electronic foetal monitoring, a relationship between foetal movement and foetal heart rate was observed and that relationship formed the basis for non-stress test (NST). Doppler USG plays an important role in foetal growth restriction (FGR) pregnancies where hemodynamic rearrangements occur in response to foetal hypoxemia. It is now proved that significant Doppler changes occur with reduction in foetal growth at a time when other foetal well-being tests are still normal. This study was done to find out the comparative usefulness of Doppler and NST in the management of FGR and severe preeclampsia and subsequent correlation with perinatal outcome.Methods: This prospective study was conducted on pregnant women with severe preeclamsia and/or FGR beyond 30 weeks of gestation at AHRR Delhi. 50 pregnancies complicated with severe preeclampsia and/or FGR beyond 30 weeks of gestation were selected. Patients meeting the inclusion criteria were subjected to NST. Umbilical arterial Doppler flow was obtained at weekly or twice weekly interval depending on the severity by pulsed wave color doppler indices were measured during foetal apnea by the same examiner at the free loop site where the clearest waveform signal could be visualized. Of 3 measurements, the mean average of S/D ratio was recorded and followed up with serial Doppler assessment and non-stress test. Data was collected and statistical analysis was carried out.Results: The Doppler showed changes earlier than NST giving a significant lead time of up to 20 days with an average of 4.94 days. The UA S/D had the highest sensitivity (88%) and diagnostic accuracy (94%) in predicting the adverse perinatal outcome. The sensitivity and specificity of Doppler as compared to NST was 82.6% and 63.0% respectively with a diagnostic accuracy of 72%. The Doppler has negative predictive value of 80.95% and positive predictive value of 65.5%. Color Doppler has diagnostic accuracy of 72%. The mortality rate in reversal of diastolic flow was 77.77% and in absent UA flow was 16.66%. 12% foetuses were found to have AEDV in UA and among them 66.66% had both FGR+PE as maternal complication. There was 83.33% rate of LSCS, 16.66% neonatal mortality rate, 83.33% NICU stay rate and 66.66% complication rate in neonates. Whereas 18% had REDV and among that 88.88% had both FGR+PE as maternal complication, a similar rate of LSCS, 77.77% rate of neonatal mortality, 100 % NICU stay and 66.66% complication rate in the neonates.Conclusions: Combined foetal testing modalities such as Doppler, NST and biophysical profile provide a wealth of information regarding foetal health. Integrated foetal testing would be ideal for individualized care of the preterm compromised foetuses for timed intervention

Ferricarboxy maltose to treat iron deficiency anemia in pregnancy: is it a feasible option?

Background: Iron deficiency is a common cause of anaemia in pregnancy which influences the health of mother and developing fetus. Intravenous (IV) iron preparations are considered, when oral iron therapy is ineffective or intolerant. Ferric carboxymaltose is an IV preparation that can be given with ease of administration and better tolerated. The aim of this study was to assess the efficacy and safety of IV ferric carboxymaltose in pregnant mother with all grades of anemia in the second and third trimester.Methods: This is a prospective observational study where 44 pregnant women with iron deficiency anemia [IDA] received ferric carboxymaltose up to 15mg/kg in second and third trimester. The parameters that were taken into account, to assess the effectiveness of the treatment was repeat haemoglobin [Hb] measurements and the subjective sense of wellbeing in the patient. The safety of the drug was analysed by continuous fetal heart rate [FHR] monitoring during the infusion and observation of any adverse reactions.Results: Ferric carboxymaltose intravenous infusion significantly increased Hb levels above baseline values in all women. The Increase in Hb levels were observed at 3- and 6-weeks post infusion therapy. FHR monitoring did not show any drug related unfavourable effect on the fetus. Of the 44 women interviewed, 33 (75%) women reported sense of well-being, 7 (15.9%) women could not feel any difference after the infusion and 4 (9.1%) patients could not comment. No serious adverse effects were noticed but minor side effects occurred in 3 (6.8%) patients.Conclusions: This prospective study showed safety and efficacy of ferric carboxymaltose in pregnancy with IDA which is consistent with available observational data

TRAIL-induced variation of cell signaling states provides nonheritable resistance to apoptosis.

TNFα-related apoptosis-inducing ligand (TRAIL), specifically initiates programmed cell death, but often fails to eradicate all cells, making it an ineffective therapy for cancer. This fractional killing is linked to cellular variation that bulk assays cannot capture. Here, we quantify the diversity in cellular signaling responses to TRAIL, linking it to apoptotic frequency across numerous cell systems with single-cell mass cytometry (CyTOF). Although all cells respond to TRAIL, a variable fraction persists without apoptotic progression. This cell-specific behavior is nonheritable where both the TRAIL-induced signaling responses and frequency of apoptotic resistance remain unaffected by prior exposure. The diversity of signaling states upon exposure is correlated to TRAIL resistance. Concomitantly, constricting the variation in signaling response with kinase inhibitors proportionally decreases TRAIL resistance. Simultaneously, TRAIL-induced de novo translation in resistant cells, when blocked by cycloheximide, abrogated all TRAIL resistance. This work highlights how cell signaling diversity, and subsequent translation response, relates to nonheritable fractional escape from TRAIL-induced apoptosis. This refined view of TRAIL resistance provides new avenues to study death ligands in general

Correlation of intra partum electronic fetal monitoring with neonatal outcome

Background: The importance of fetal monitoring during labour has been realized since long. The stress of uterine contractions may affect the fetus adversely especially if the fetus is already compromised, when the placental reserves are suboptimal, or when cord undergoes compression as in those associated with diminished liquor amnii or iatrogenic uterine hyperstimulation due to injudicious use of oxytocin. Even a fetus which is apparently normal in the antenatal period may develop distress during labour. Hence fetal monitoring during antepartum and intrapartum periods is of vital importance for timely detection of fetal distress so that appropriate management may be offered.Methods: This study was a prospective observational study included 100 patients of more than 34 weeks period of gestation were divided into two groups. Patients in labour were analyzed on an Electronic Monitor. Delivery conducted was either by vaginal route, instrumental or by caesarean section depending upon the fetal heart rate tracings and their interpretations as per the case. At the time of delivery umbilical cord blood was taken for the pH analysis. All new born babies were seen by the paediatrician immediately after the delivery and 1 and 5 minute APGAR score assessed for the delivered baby. The various EFM Patterns obtained were compared with the neonatal status at birth using the parameters already mentioned. The false positives and false negatives if any were tabulated. Data so obtained was analyzed statistically thereafter. Statistical Package for Social Sciences (SPSS) Version 13.0 was used for the purpose of analysis.Results: Results revealed that among the 50 subjects of the case group, 7 subjects showed the absence of the beat to beat variability, 12 subjects showed early deceleration, 32 subjects showed late deceleration, and 6 subjects showed the presence of variable deceleration. No significant association of beat to beat variability, early and variable deceleration could be established with meconium staining/NICU admissions/low APGAR. A significant positive association between persistent late deceleration with MSL, APGAR <7 at 1 min, and Instrumental/LSCS delivery was seen. A significant positive association between any CTG abnormality and APGAR at 1 min, type of delivery, and meconium staining was seen.Conclusions: EFM should be used judiciously. Cardiotocography machines are certainly required in the labour room. Equally important is the proper interpretation of the CTG tracings so that unjustified caesarean sections can be minimized, at the same time picking up cases of fetal distress in time which is likely to improve fetal outcome

Antenatally diagnosed congenital anomalies-trend in tertiary care hospital

Background: Antenatally diagnosed, congenital abnormalities of the fetus are frequently offered antenatal surgical consultation in all tertiary care hospitals to adequately counsel prospective parents. We aimed to assess the current trends in antenatally diagnosed congenital malformations of fetus in patients who had presented to our hospital for reassessment or surgical consultation and these patients were counselled and prognosticated after confirmation of anomaly at our centre accordingly.Methods: This was a retrospective study of all the cases diagnosed antenatally with fetal abnormalities. All cases were referred to either pediatric surgery outpatient department or fetal medicine subunit of a tertiary care centre from January 2017-December 2018. The complete records of these pregnant women were perused, presence and type of anomaly confirmed at our centre and trends about types of anomalies analysed.Results: A total of 209 women were analyzed for antenatal anomalies, out of these patients medical termination of pregnancy was offered to 27 (12.9%) patients, in which 38 anomalies were detected and in 182 (87%) patients pregnancy was continued to delivery. A total of 223 anomalies were detected in this group with some patients having fetuses with more than one anomaly. Gastrointestinal abnormalities were present in 94 (51.6%) patients of those who delivered and accounted for the most common anomaly followed by CNS abnormality which accounted for 39 (21.4%) of total abnormalities and genitourinary abnormalities contributed to 28 (13.3%) of abnormalities. A total of 85.2% of patients were referred after 20 weeks.Conclusions: The significant number of patients with major congenital anomalies are still diagnosed at a date later than permissible time for termination of gestation (20 weeks). There were cases where anomaly scan was done at a later gestation and then there were others where inadequate counselling made patient to present late for prognostication. However, there are certain anomalies that are picked up late and are likely to be missed in the routine anomaly scan. Therefore, antenatal detection and early referral helps in offering early counselling and better outcome for pregnancy.

A case of valproate induced non-hepatic hyperammonemic encephalopathy

Sodium valproate is a broad spectrum anticonvulsant. Valproate induced hyperammonemic encephalopathy with normal liver function is a serious, but less common entity

Rituximab therapy in pulmonary alveolar proteinosis improves alveolar macrophage lipid homeostasis

Rationale Pulmonary Alveolar Proteinosis (PAP) patients exhibit an acquired deficiency of biologically active granulocyte-macrophage colony stimulating factor (GM-CSF) attributable to GM-CSF specific autoantibodies. PAP alveolar macrophages are foamy, lipid-filled cells with impaired surfactant clearance and markedly reduced expression of the transcription factor peroxisome proliferator-activated receptor gamma (PPARγ) and the PPARγ-regulated ATP binding cassette (ABC) lipid transporter, ABCG1. An open label proof of concept Phase II clinical trial was conducted in PAP patients using rituximab, a chimeric murine-human monoclonal antibody directed against B lymphocyte specific antigen CD20. Rituximab treatment decreased anti-GM-CSF antibody levels in bronchoalveolar lavage (BAL) fluid, and 7/9 patients completing the trial demonstrated clinical improvement as measured by arterial blood oxygenation. Objectives This study sought to determine whether rituximab therapy would restore lipid metabolism in PAP alveolar macrophages. Methods BAL samples were collected from patients pre- and 6-months post-rituximab infusion for evaluation of mRNA and lipid changes. Results Mean PPARγ and ABCG1 mRNA expression increased 2.8 and 5.3-fold respectively (p ≤ 0.05) after treatment. Lysosomal phospholipase A2 (LPLA2) (a key enzyme in surfactant degradation) mRNA expression was severely deficient in PAP patients pre-treatment but increased 2.8-fold post-treatment. In supplemental animal studies, LPLA2 deficiency was verified in GM-CSF KO mice but was not present in macrophage-specific PPARγ KO mice compared to wild-type controls. Oil Red O intensity of PAP alveolar macrophages decreased after treatment, indicating reduced intracellular lipid while extracellular free cholesterol increased in BAL fluid. Furthermore, total protein and Surfactant protein A were significantly decreased in the BAL fluid post therapy. Conclusions Reduction in GM-CSF autoantibodies by rituximab therapy improves alveolar macrophage lipid metabolism by increasing lipid transport and surfactant catabolism. Mechanisms may involve GM-CSF stimulation of alveolar macrophage ABCG1 and LPLA2 activities by distinct pathways

Systems medicine dissection of chr1q-amp reveals a novel PBX1-FOXM1 axis for targeted therapy in multiple myeloma

Understanding the biological and clinical impact ofcopy number aberrations (CNA)for the development of precision therapies in cancer remains anunmet challenge. Genetic amplification of chromosome 1q (chr1q-amp) is a major CNAconferring adverse prognosis in several types of cancer, including in the blood cancer multiple myeloma (MM). Although severalgenes across chr1q portend high-risk MM disease, the underpinning molecular aetiology remains elusive. Here, with reference to the 3D chromatin structure, we integrate MMpatient multi-omics datasets with genetic variables to obtain an associated clinical risk map across chr1q and to identify 103 adverse prognosis genes in chr1q-amp MM. Prominent amongst these genes, the transcription factor PBX1 is ectopically expressed by genetic amplification and epigenetic activation of its own preserved 3D regulatory domain. By binding to reprogrammed super-enhancers, PBX1 directly regulates critical oncogenic pathways and a FOXM1-dependent transcriptional programme. Together, PBX1 and FOXM1 activate a proliferative gene signature which predicts adverse prognosis across multiple types of cancer. Notably, pharmacological disruption of the PBX1-FOXM1 axis with existing agents (thiostrepton) and a novel PBX1 small-molecule inhibitor (T417) is selectively toxic against chr1q-amplified myeloma and solid tumour cells. Overall, our systems medicine approach successfully identifies CNA-driven oncogenic circuitries, links them to clinical phenotypes and proposes novel CNA-targeted therapystrategies in multiple myeloma and other types of cancer