Safety and Tolerability of Continuous Inhaled Iloprost Therapy for Severe Pulmonary Hypertension in Neonates and Infants.

This is a single-center retrospective study to assess the safety and tolerability of continuous inhaled iloprost use as rescue therapy for refractory pulmonary hypertension (PH) in critically ill neonates and infants. A retrospective chart review was performed on 58 infants and data were collected at baseline, 1, 6, 12, 24, 48 and 72 h of iloprost initiation. Primary outcomes were change in heart rate (HR), fraction of inspired oxygen (FiO2), mean airway pressures (MAP), blood pressure (BP) and oxygenation index (OI). Secondary outcomes were need for extracorporeal membrane oxygenation (ECMO) and death. 51 patients treated for >6 h were analyzed in 2 age groups, neonate (≤28 days: n = 32) and infant (29-365 days: n = 19). FiO2 (p < 0.001) and OI (p = 0.01) decreased, while there were no significant changes in MAP, BP and HR. Of the fifteen patients placed on ECMO, seven were bridged off ECMO on iloprost and eight died. Twenty-four out of fifty-one patients (47%) recovered without requiring ECMO, while twelve (23%) died. Iloprost as add-on therapy for refractory PH in critically ill infants in the NICU has an acceptable tolerability and safety profile. Large prospective multicenter studies using iloprost in the neonatal ICU are necessary to validate these results.

Mechanism of drug resistance in HIV-1 protease subtype C in the presence of Atazanavir.

AIDS is one of the deadliest diseases in the history of humankind caused by HIV. Despite the technological development, curtailing the viral infection inside human host still remains a challenge. Therapies such as HAART uses a combination of drugs to inhibit the viral activity. One of the important targets includes HIV protease and inhibiting its activity will minimize the production of mature structural proteins. However, the genetic diversity and the occurrence of drug resistant mutations adds complexity to effective drug design. In this study, we aimed at understanding the drug binding mechanism of one such subtype, namely subtype C and its insertion variant L38HL. We performed multiple molecular dynamics simulations along with binding free energy analysis of wild-type and L38HL bound to Atazanavir (ATV). From the analysis, we revealed that the insertion alters the hydrogen bond and hydrophobic interaction networks. The alterations in the interaction networks increase flexibility at the hinge-fulcrum interface. Further, the effects of these changes affect flap tip curling. Moreover, the changes in the hinge-fulcrum-cantilever interface alters the concerted motion of the functional regions leading to change in the direction of flap movement thus causing a subtle change in the active site volume. Additionally, formation of intramolecular hydrogen bonds in the ATV docked to L38HL restricted the movement of R1 and R2 groups thereby altering the interactions. Overall, the changes in the flexibility of flap together with the changes in the active site volume and compactness of the ligand provide insights for increased binding affinity of ATV with L38HL.

Approach to dyspnoea in pregnancy in the COVID-19 era.

IMPORTANCE: Dyspnoea and hypoxia in pregnant women during the COVID-19 pandemic may be due to causes other than SARS Co-V-2 infection which should not be ignored. Shared decision-making regarding early delivery is paramount. OBJECTIVE: To highlight and discuss the differential diagnoses of dyspnoea and hypoxia in pregnant women and to discuss the risks versus benefit of delivery for maternal compromise. DESIGN, SETTING AND PARTICIPANTS: Case series of two pregnant women who presented with dyspnoea and hypoxia during the COVID-19 pandemic. RESULTS: Two pregnant women presented with dyspnoea and hypoxia. The first case had COVID-19 infection in the 3rd trimester. The second case had an exacerbation of asthma without concurrent COVID-19. Only the first case required intubation and delivery. Both recovered and were discharged home. Conclusion and relevance: Our two cases highlight the importance of making the correct diagnosis and timely decision-making to consider if delivery for maternal compromise is warranted. Whilst COVID-19 is a current healthcare concern other differential diagnoses must still be considered when pregnant women present with dyspnoea and hypoxia.

SARS-CoV-2 Infection in Patients with Down Syndrome, Congenital Heart Disease, and Pulmonary Hypertension: Is Down Syndrome a Risk Factor?

With increasing information available about the epidemiology, pathophysiology, and management of patients affected with severe acute respiratory syndrome corona virus-2 infection, patients with Down syndrome, congenital heart disease, airway obstruction, and pulmonary hypertension present a unique challenge. This case series describes 3 patients with Down syndrome and respiratory failure secondary to coronavirus infection.

A descriptive single-centre experience of the management and outcome of maternal alloantibodies in pregnancy.

BACKGROUND: Haemolytic disease of the fetus and newborn (HDFN) occurs when maternal IgG alloantibodies to fetal red blood cell antigens cross the placenta, causing haemolysis in the fetus and/or neonate. After delivery, the main concern is hyperbilirubinaemia, which can cause neurological damage. OBJECTIVES: To summarise our current management and outcome data to inform health-care professionals counselling women whose pregnancies are at risk of HDFN and to compare these data with relevant studies. METHODS: This is a retrospective descriptive study of all high-risk pregnancies at risk of HDFN at Guy's and St. Thomas' NHS Foundation Trust (GSTFT) Maternity Unit over a 7-year period. We defined high-risk pregnancies as those in whom anti-D, anti-c, anti-K or high (>32 or doubling strength) titres of all other antibodies were identified. RESULTS: A total of 130 pregnancies in 112 women were followed up. A single alloantibody was found in 93 pregnancies (71.5%) and multiple alloantibodies in 37 pregnancies (28.5%). Anti-D was most commonly encountered (n = 48, 36.9%), followed by anti-c (n = 31, 23.8%) and anti-E (n = 15, 11.5%). In 65 of 130 pregnancies (50%), antibody concentrations triggered scans to screen for fetal anaemia. Of 130 pregnancies, 6 (4.6%) required intrauterine transfusions, and 31 of 130 (26%) neonates required post-natal intervention. Overall, morbidity was 0.1% and mortality 0.002%. CONCLUSIONS: This study demonstrates that morbidity and mortality caused by HDFN is minimal. These results are reassuring for women at risk of HDFN as even severely affected cases are successfully managed in most instances. Further studies are needed to identify predictors of disease severity.

Photoresponsive, reversible immobilization of virus particles on supramolecular platforms.

Here we report on the covalent attachment of photoresponsive azobenzene moieties to cowpea chlorotic mottle virus (CCMV). The modified virus capsids can be reversibly immobilized on cucurbit[8]uril (CB[8]) bearing surfaces via supramolecular complexation.

Short-term outcome of periviable small-for-gestational-age babies: is our counseling up to date?

OBJECTIVE: There are limited data for counseling on and management of periviable small-for-gestational-age (SGA) fetuses. We therefore aimed to investigate the short-term outcome of periviable SGA fetuses in relation to the likely underlying cause. METHODS: This was a retrospective study of data from three London tertiary fetal medicine centers obtained between 2000 and 2015. We included viable singleton pregnancies with a severely small fetus, defined as those with an abdominal circumference ≤ 3rd percentile, identified between 22 + 0 and 25 + 6 weeks' gestation. Data obtained included fetal biometry, presence of placental anomalies, uterine and fetal Doppler and neonatal outcome. We excluded cases with structural abnormalities, proven or suspected abnormal karyotype or genetic syndromes. Cases were classified according to the suspected underlying cause of the small fetal size into one of the following categories: uteroplacental insufficiency, evidence of placental damage with normal uterine artery Doppler, viral infection, or unclassied. RESULTS: There were 245 cases included in the study. Of these, at diagnosis of SGA, 201 (82%) were categorized as uteroplacental cause, 13 (5%) as suspected placental cause, one (0.4%) as suspected viral cause and 30 (12%) could not be assigned to any of these categories. Overall, 101 (41%) cases survived the neonatal period; 89 (36%) underwent in-utero fetal demise, 22 (9%) died neonatally and 33 (14%) pregnancies were terminated. The diagnosis-to-delivery interval was 8.1 weeks in those that survived and 4.5 weeks in those that died neonatally. CONCLUSIONS: Almost 90% of periviable SGA cases are associated with uteroplacental insufficiency or intraplacental damage. Survival is related to gestational age at delivery, with outcomes better than might be assumed at diagnosis and some pregnancies reaching term. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

MobileHeart, a mobile smartphone-based application that supports and monitors coronary artery disease patients during rehabilitation.

Conventional center-based cardiac rehabilitation adherence is poor, adversely affecting long-term efficacy. Innovative strategies such as telerehabilitation are perceived as promising alternatives to improve care delivery. This paper presents the results of prior and ongoing work on the design and development of MobileHeart, a telemedical smartphone-based application to be used in secondary prevention for ischemic heart disease patients. Its constituent components are discussed separately, the minimal necessary cardiovascular monitoring requirements are elaborated in more detail. The results are offered starting from a clinical perspective to stress its relevance in the establishment of scientifically/medically sound programs.

Dichorionic triplet pregnancies: risk of miscarriage and severe preterm delivery with fetal reduction versus expectant management. Outcomes of a cohort study and systematic review.

BACKGROUND: In trichorionic pregnancies, fetal reduction from three to two lowers the risk of severe preterm delivery, but provides no advantage in survival. Similar data for dichorionic triamniotic (DCTA) triplets is not readily available. OBJECTIVES: To document the natural history of DCTA triplets and the effect of reduction on the risk of miscarriage and severe preterm delivery, compared with expectant management. SEARCH STRATEGY: Systematic search on MEDLINE, EMBASE, and the Cochrane Library. SELECTION CRITERIA: DCTA triplets with three live fetuses at 8-14 weeks of gestation, outcome data with expectant management and/or reduction, miscarriage before 24 weeks of gestation and/or severe preterm delivery before 32-33 weeks of gestation. DATA COLLECTION AND ANALYSIS: Five studies were included. Data from these were combined with data from three centres. MAIN RESULTS: There were 331 DCTA triplets. The miscarriage rate was 8.9% (95% CI 5.8-13.3%) and the severe preterm delivery rate was 33.3% (95% CI 27.5-39.7%), with expectant management. The miscarriage rate was 14.5% (95% CI 7.6-26.2%) with a reduction of the monochorionic pair, 8.8% (95% CI 3.0-23.0%) with a reduction of one fetus of the monochorionic pair, and 23.5% (9.6-47.3%) with a reduction of the fetus with a separate placenta. Severe preterm delivery rates were 5.5% (95% CI 1.9-14-9%), 11.8% (95% CI 4.7-26.6%), and 17.6% (95% CI 6.2-41.0%), respectively. CONCLUSIONS: In DCTA triplets, expectant management is a reasonable choice when the top priority is a liveborn infant. Where the priority is to minimise severe preterm delivery, the most advisable option is fetal reduction. Further studies are needed to clarify which particular technique is advisable to optimise the outcome.

Meta-analysis of gut barrier dysfunction in patients with acute pancreatitis.

BACKGROUND: The gut is implicated in the pathogenesis of acute pancreatitis but there is discrepancy between individual studies regarding the prevalence of gut barrier dysfunction in patients with acute pancreatitis. The aim of this study was to determine the prevalence of gut barrier dysfunction in acute pancreatitis, the effect of different co-variables, and changes in gut barrier function associated with the use of various therapeutic modalities. METHODS: A literature search was performed using PRISMA and MOOSE guidelines. Summary estimates were presented as pooled prevalence of gut barrier dysfunction and the associated 95 per cent c.i. RESULTS: A total of 44 prospective clinical studies were included in the systematic review, of which 18 studies were subjected to meta-analysis. The pooled prevalence of gut barrier dysfunction was 59 (95 per cent c.i. 48 to 70) per cent; the prevalence was not significantly affected by disease severity, timing of assessment after hospital admission or type of test used, but showed a statistically significant association with age. Overall, nine of 13 randomized clinical trials reported a significant improvement in gut barrier function following intervention compared with the control group, but only three of six studies that used standard enteral nutrition reported a statistically significant improvement in gut barrier function after intervention. CONCLUSION: Gut barrier dysfunction is present in three of five patients with acute pancreatitis, and the prevalence is affected by patient age but not by disease severity. Clinical studies are needed to evaluate the effect of enteral nutrition on gut function in acute pancreatitis.

Optical control over bioactive ligands at supramolecular surfaces.

In this communication we report for the first time the use of azobenzene modified glycoconjugates to establish optical control over bioactive ligands at a supramolecular ß-cyclodextrin (ß-CD) surface. Several studies were conducted to investigate the photoresponsive immobilization of proteins and bacteria on these supramolecular surfaces.

Prospective evaluation of 125 consecutive laparoscopic myomectomies.

With technological advancement and increasing skill in minimal access surgery, laparoscopic myomectomy is increasingly performed for the management of symptomatic fibroids in appropriately selected women. We present a series of 125 consecutive laparoscopic myomectomies to assess whether the number, size and location of fibroids affect the length of hospital stay. Total of 462 myomas were removed from 125 patients. The mean size of fibroids removed was 7.6 cm and the mean number of fibroids was 3.69. None of our patients had major intraoperative complication involving bladder or bowel. Our laparotomy conversion rate was 1.6% (2 out of 125). There was no significant difference based on size, number or weight of fibroids removed in relation to the day of discharge in our series. We conclude that the size and number of fibroids removed do not affect the day of discharge.

Integrated approach for demarcating subsurface pollution and saline water intrusion zones in SIPCOT area: a case study from Cuddalore in Southern India.

This paper deals with a systematic hydrogeological, geophysical, and hydrochemical investigations carried out in SIPCOT area in Southern India to demarcate groundwater pollution and saline intrusion through Uppanar River, which flows parallel to sea coast with high salinity (average TDS 28, 870 mg/l) due to back waters as well as discharge of industrial and domestic effluents. Hydrogeological and geophysical investigations comprising topographic survey, self-potential, multi-electrode resistivity imaging, and water quality monitoring were found the extent of saline water intrusion in the south and pockets of subsurface pollution in the north of the study area. Since the area is beset with highly permeable unconfined quaternary alluvium forming potential aquifer at shallow depth, long-term excessive pumping and influence of the River have led to lowering of the water table and degradation of water quality through increased salinity there by generating reversal of hydraulic gradient in the south. The improper management of industrial wastes and left over chemicals by closed industries has led surface and subsurface pollution in the north of the study area.

Relationship of intertwin crown-rump length discrepancy to chorionicity, fetal demise and birth-weight discordance.

OBJECTIVES: To study the frequency and clinical significance of crown-rump length (CRL) discrepancy at 11-14 weeks of gestation in twin pregnancies from an unselected population. METHODS: This was a retrospective analysis of all twin pregnancies that underwent a routine 11-14-week scan at a large teaching hospital. Fetal loss was defined as fetal demise of one or both twins after 14 weeks. RESULTS: A total of 507 twin pregnancies were studied; 382 (75.3%) were dichorionic and 125 (24.7%) were monochorionic twins. The discrepancy in CRL was expressed as a percentage of the CRL of the larger twin. The 95(th) and 99(th) centile for CRL discrepancy in twins was 12.2% and 19.3%, respectively. The discrepancy in CRLs in monochorionic and dichorionic twins was not significantly different (Mann-Whitney U = 22,406, P = 0.302). In 39 twin pairs, there was subsequent intrauterine death of one or both twins. Fetal loss was more common in monochorionic twins (24/125) than in dichorionic twins (15/382) (chi-square = 30.9, P < 0.001). In monochorionic twins, the discrepancy in CRLs in the 24 cases with subsequent loss was significantly greater than in the 101 twin pairs with no subsequent loss (Mann-Whitney U = 896, P = 0.048). The discrepancy in CRLs in 15 dichorionic twins with subsequent loss was not different from that in the 367 twins with no loss (Mann-Whitney U = 2116.5, P = 0.129). The CRL discrepancy was significantly correlated with birth-weight discordance in twins (Spearman's rho = 0.128, P = 0.006). However, this was due to a significant correlation in dichorionic twins (Spearman's rho = 0.127, P = 0.016) but not in monochorionic twins (Spearman's rho = 0.145, P = 0.14). CONCLUSIONS: Fetal loss is significantly associated with discrepancy in CRL at the 11-14-week scan in monochorionic twins and discordance in birth weights is significantly associated with discrepancy in CRL in dichorionic twins. However, intertwin CRL discrepancy is of limited value in screening for these adverse events.

The prediction of intra-partum fetal compromise in prolonged pregnancy.

This is a prospective study conducted in a dedicated post-dates clinic to investigate the importance of antenatal ultrasound, Doppler and cardiotocographic (CTG) indices in the prediction of adverse intra-partum events in prolonged pregnancy. Operative delivery for abnormal fetal ECG-ST segment analysis and/or an arterial cord pH < 7.15 were regarded as adverse events. There were 462 singleton pregnancies with 87 adverse intra-partum events included in the analysis. Intra-partum adverse events were associated with nulliparity, oligohydramnios and induction of labour. The birth weight of fetuses was significantly less in the group with adverse intra-partum events. Logistic regression analysis showed that only nulliparity, birth weight and oligohydramnios had a significant independent influence on the risk of an adverse intra-partum event. Nulliparity was associated with five-fold increase in risk of an adverse intra-partum event. Oligohydramnios was associated with a three-fold increase in the risk. The risk decreased with increasing birth weight.

Effective CD4+ T-cell restoration in gut-associated lymphoid tissue of HIV-infected patients is associated with enhanced Th17 cells and polyfunctional HIV-specific T-cell responses.

Human immunodeficiency virus (HIV) infection leads to severe CD4+ T-cell depletion in gut-associated lymphoid tissue (GALT) that persists despite the initiation of highly active antiretroviral therapy (HAART). It is not known whether restoration of gut mucosal CD4+ T cells and their functions is feasible during therapy and how that relates to immune correlates and viral reservoirs. Intestinal biopsies and peripheral blood samples from HIV-infected patients who were either HAART naive or on long-term HAART were evaluated. Our data demonstrated that gut CD4+ T-cell restoration ranged from modest (<50%) to high (>50%), compared with uninfected controls. Despite persistent CD4+ T-cell proviral burden and residual immune activation in GALT during HAART, effective CD4+ T-cell restoration (>50%) was achieved, which was associated with enhanced Th17 CD4+ T-cell accumulation and polyfunctional anti-HIV cellular responses. Our findings suggest that a threshold of>50% CD4+ T-cell restoration may be sufficient for polyfunctional HIV-specific T cells with implications in the evaluation of vaccines and therapeutics.