Bench-to-bedside imaging in brain metastases: a road to precision oncology.

Radiology has seen tremendous evolution in the last few decades. At the same time, oncology has made great strides in diagnosing and treating cancer. Distant metastases of neoplasms are being encountered more often in light of longer patient survival due to better therapeutic strategies and diagnostic methods. Brain metastasis (BM) is a dismal manifestation of systemic cancer. In the present scenario, magnetic resonance imaging (MRI), computed tomography (CT) and positron emission tomography (PET) are playing a big role in providing molecular information about cancer. Lately, molecular imaging has emerged as a stirring arena of dynamic imaging techniques that have enabled clinicians and scientists to noninvasively visualize and understand biological processes at the cellular and molecular levels. This knowledge has impacted etiopathogenesis, detection, personalized treatment, drug development, and our understanding of carcinogenesis. This article offers insight into the molecular biology underlying brain metastasis, its pathogenesis, imaging protocols, and algorithms. It also discusses disease-specific molecular imaging features, focusing on common tumors that spread to the brain, such as lung, breast, colorectal cancer, melanoma, and renal cell carcinoma. Additionally, it covers various targeted treatment options, criteria for assessing treatment response, and the role of artificial intelligence in diagnosing, managing, and predicting prognosis for patients with brain metastases.

Clinicopathological Profile and Survival Outcomes in Patients with Localised Extremity Synovial Sarcomas.

AIMS: Synovial sarcoma is a rare but aggressive variant of soft-tissue sarcoma. Literature is sparse and reported mostly from the West. We analysed the clinical profiles and prognostic factors of extremity synovial sarcoma patients in order to study their clinical journey. MATERIALS AND METHODS: This was a retrospective analysis. All patients with extremity synovial sarcoma treated between 1992 and 2020 were included. Patients with metastases at presentation were excluded. A descriptive analysis of demographic and clinicopathological features of patients undergoing limb salvage surgery (LSS) or amputation was carried out. Overall survival and disease-free survival were calculated for the entire cohort as well as for the LSS and amputation groups. Factors prognostic for survival were identified. RESULTS: In total, 157 patients had localised extremity synovial sarcoma. Predominantly, young adults (median 31 years) and males (61%) were affected. Over 70% of patients presented after recurrence or unplanned surgeries. Sixty-seven per cent of tumours were >5 cm, 69% were deep and 23% involved bone. The limb salvage rate was 64%. In the LSS group, adjuvant radiotherapy and chemotherapy were given to 72% and 68% of patients, respectively. In the amputation group, 72% of patients received adjuvant chemotherapy. In a median follow-up of 59 months, 39.4% of patients had recurrences, the majority (61.2%) were systemic. Five-year overall survival and disease-free survival were 53.4% and 49.8%, respectively. Overall survival was 63.9% and 29.7% in the LSS and amputation groups, respectively. On multivariate analysis, tumour size, depth, omission of radiotherapy and bone invasion were found to be the adverse prognostic factors. CONCLUSION: This is one of the largest studies on extremity synovial sarcoma. Mostly males and young adults were affected. The limb salvage rate was 64%, despite most being referred after unplanned surgery. Almost 70% of patients received radiotherapy and chemotherapy. Overall survival was inferior in the amputation group. Tumour size >5 cm, depth and bone invasion were negative, whereas adjuvant radiotherapy was a positive prognostic factor for survival. Chemotherapy had no impact on survival.

Post-treatment imaging of gliomas: challenging the existing dogmas.

Gliomas are the commonest malignant central nervous system tumours in adults and imaging is the cornerstone of diagnosis, treatment, and post-treatment follow-up of these patients. With the ever-evolving treatment strategies post-treatment imaging and interpretation in glioma remains challenging, more so with the advent of anti-angiogenic drugs and immunotherapy, which can significantly alter the appearance in this setting, thus making interpretation of routine imaging findings such as contrast enhancement, oedema, and mass effect difficult to interpret. This review details the various methods of management of glioma including the upcoming novel therapies and their impact on imaging findings, with a comprehensive description of the imaging findings in conventional and advanced imaging techniques. A systematic appraisal for the existing and emerging techniques of imaging in these settings and their clinical application including various response assessment guidelines and artificial intelligence based response assessment will also be discussed.

Outcomes among preterm infants with patent ductus arteriosus: Relationship with treatment, gestational age, hemodynamic status and timing of treatment.

BACKGROUND: There remains controversy regarding the outcomes resulting from treatment versus conservative management of patent ductus arteriosus (PDA) among preterm infants. The effects of extreme prematurity, hemodynamic status of the PDA, and age at treatment remain poorly defined. STUDY DESIGN: This retrospective case-control study including infants < 1250 gm who were categorized into 3 groups: Group 1: without PDA, Group 2: with untreated PDA, and Group 3: treated PDA. Diagnosis and treatment of PDA extracted from the medical records. Demographics, clinical characteristics, and outcomes compared using chi-square and analysis of variance. Logistic regression used to estimate adjusted odds ratios. RESULTS: The study included 734 infants, with 141(19%) in Group 1, 329 (45%) in 2, and 264 (36%) in 3. Group 3 had higher incidence of bronchopulmonary dysplasia (BPD) (aOR, 2.9; 95%CI 1.7-4.8). Infant treated for hemodynamically significant PDA (HSPDA) had higher incidence of BPD (aOR, 1.9; 95%CI 1.0-3.8) and retinopathy of prematurity (ROP) (aOR, 3.4; 95%CI 1.6-6.9). There were no differences in outcome associated with treatment among≤26 weeks gestation and the age when treated. CONCLUSION: Infants with PDA who were treated had higher incidence of BPD. Among those who were treated, those with HSPDA had a higher incidence of BPD and ROP.

Microbial community in human gut: a therapeutic prospect and implication in health and diseases.

The interest in the working and functionality of the human gut microbiome has increased drastically over the years. Though the existence of gut microbes has long been speculated for long over the last few decades, a lot of research has sprung up in studying and understanding the role of gut microbes in the human digestive tract. The microbes present in the gut are highly instrumental in maintaining the metabolism in the body. Further research is going on in this field to understand how gut microbes can be employed as potential sources of novel therapeutics; moreover, probiotics have also elucidated their significant place in this direction. As regards the clinical perspective, microbes can be engineered to afford defence mechanisms while interacting with foreign pathogenic bodies. More investigations in this field may assist us to evaluate and understand how these cells communicate with human cells and promote immune interactions. Here we elaborate on the possible implication of human gut microbiota into the immune system as well as explore the probiotics in the various human ailments. Comprehensive information on the human gut microbiome at the same platform may contribute effectively to our understanding of the human microbiome and possible mechanisms of associated human diseases.

Efficacy of middle-ear packing in success of type 1 tympanoplasty: a prospective randomised study.

OBJECTIVE: A prospective randomised study was undertaken to compare the results of type 1 tympanoplasty with and without middle-ear packing with gelfoam. METHOD: Eighty patients undergoing type 1 tympanoplasty were randomised into two groups according to packing in the middle ear: with gelfoam and without gelfoam. The data in terms of graft uptake rate, hearing gain and subjective improvement were analysed at one and three months. RESULTS: The graft uptake rate between both groups did not show a statistically significant difference. There was conductive hearing loss in the gelfoam group in the early post-operative period. Subjectively, patients were more comfortable with respect to heaviness and hearing gain than in the non-gelfoam group. CONCLUSION: Gelfoam use in middle-ear packing is not an essential step and causes more discomfort in patients during the early post-operative period. It should be a surgeon's choice to use it when and where it is necessary.

The long noncoding RNA MALAT1 suppresses miR-211 to confer protection from ultraviolet-mediated DNA damage in vitiligo epidermis by upregulating sirtuin 1.

BACKGROUND: The absence of melanocytes poses a challenge for long-term tissue homeostasis in vitiligo. Surprisingly, while individuals with Fitzpatrick phototypes I-II (low melanin content) have a higher incidence of melanoma and nonmelanoma skin cancer, people with vitiligo are at a decreased risk for the same. OBJECTIVES: To understand the molecular mechanisms that protect vitiligo skin from ultraviolet (UV)-induced DNA damage by (i) characterizing differentially expressed microRNAs in lesional vs. nonlesional epidermis and (ii) identifying their upstream regulators and downstream gene targets. METHODS: Genome-wide microRNA profiling of nonlesional and lesional epidermis was performed on five individuals with stable nonsegmental vitiligo using next-generation RNA sequencing. The relevance of the upstream regulator and downstream target gene of the most differentially expressed microRNA was studied. RESULTS: Our study found sirtuin1 (SIRT1), an NAD-dependent deacetylase, to be a direct target of miR-211 - the most significantly downregulated microRNA in lesional epidermis. Inhibition of SIRT1 with EX-527 downregulated keratin 10 and involucrin, suggesting that SIRT1 promotes keratinocyte differentiation. Overexpression of miR-211 mimic led to a significant increase in γ-H2AX positivity and cyclobutane pyrimidine dimer (CPD) formation, hallmarks of UVB-mediated DNA damage. These effects could be ameliorated by the addition of resveratrol, a SIRT1 activator. Furthermore, a long noncoding RNA, MALAT1, was identified as a negative upstream regulator of miR-211. Overexpression of MALAT1 resulted in increased expression of SIRT1 and a concomitant removal of UVB-induced CPDs in primary keratinocytes. CONCLUSIONS: These findings establish a novel MALAT1-miR-211-SIRT1 signalling axis that potentially confers protection to the 'amelanotic' keratinocytes in vitiligo.

Roflumilast counteracts DMH-induced preneoplastic colon damage in albino Wistar rats.

OBJECTIVE: The study explored the chemoprophylactic potential of roflumilast against 1,2-dimethylhydrazine (DMH) actuated preneoplastic colon damage in albino Wistar rats. METHODS: Animals were arbitrarily divided into five groups of six animals each. DMH was used to induce preneoplastic colon damage (20 mg/kg/7 days, subcutaneously, for 42 days). Roflumilast was administered subcutaneously at two doses (1 and 5 mg/kg/day, from day 28 to 42). At the end of the study, the animals were recorded for the electrocardiographic changes and heart rate variability (HRV) paradigms on 42nd day, using PowerLab system. Blood samples were collected from all the animals to measure hydrogen sulfide (H2S) and nitric acid. The colon tissue was dissected out and analyzed for inflammatory markers, biochemical parameters including, superoxide dismutase, thiobarbituric acid reactive substances, catalase, and glutathione reductase and histopathology. RESULTS: DMH caused derangement of HRV factors, abnormal antioxidant markers, and elevated levels of inflammatory markers. H2S and nitric oxide levels upsurge in DMH-treated rats and promoted preneoplastic damage. Histopathologically, loss of crypts, goblet cells, and distorted lamina propria were observed in toxic group. Treatment with roflumilast was able to curtail down oxidative stress and inflammatory markers and stabilitate the hemodynamic derangements as well as was able to restore the normal architecture of colonic mucosa. CONCLUSION: The findings from the present study conclude that treatment with roflumilast positively modulates the preneoplastic colon damage.

Associations of cutaneous and extracutaneous infections with hidradenitis suppurativa in U.S. children and adults.

BACKGROUND: Hidradenitis suppurativa (HS) is associated with bacterial colonization, skin-barrier disruption, immune dysregulation and treatments that can increase infection risk. OBJECTIVES: To determine whether HS is associated with cutaneous and extracutaneous infections and related outcomes. METHODS: Data from the 2002-2012 National Inpatient Sample were analysed, including a 20% sample of U.S. hospitalizations (n = 87 053 155). RESULTS: The prevalence (with 95% confidence interval) of infections was higher in adults (34·0%, 33·2-34·7% vs. 23·4%, 23·2-23·6%) and children (31·8%, 28·7-34·9% vs. 12·6% (12·1-13·1%) with vs. without HS. Inpatients with HS had higher prevalences of infections overall (excluding cellulitis and erysipelas) than those with psoriasis, but lower than those with atopic dermatitis. In multivariable logistic regression models adjusting for sociodemographics, HS was associated with 18 of 45 infections examined (adults: 16 of 45; children: six of 45), including acute infections (herpes simplex virus, herpes zoster, necrotizing fasciitis, septicaemia, bone infection, Clostridium difficile, methicillin-sensitive and methicillin-resistant Staphylococcus aureus, Streptococcus, Pseudomonas, mycobacterial, fungal, viral), chronic infections (HIV, hepatitis B) and antibiotic-resistant infections. HS alone was associated with increased infections. Patients with comorbid cancer; HIV; cardiometabolic, autoimmune or mental health diagnoses or acne had even higher odds of infections. Inpatients with HS with vs. without serious infection had increased inpatient mortality (0·71% vs. 0·16%), mean length of stay (7·3 vs. 4·8 days) and cost of care (US$13 578 vs. $9242), with a mean annual excess 41 050 days and $71 622 339 cost of hospitalization. CONCLUSIONS: Adults and children with HS had increased acute and chronic, cutaneous, extracutaneous and systemic infections, which were associated with increased mortality and cost. What's already known about this topic? Little is known about the risk of infection in patients with hidradenitis suppurativa (HS). What does this study add? Adults and children with HS had increased cutaneous, extracutaneous and systemic infections, at even higher rates than in patients with psoriasis and atopic dermatitis. These infections were associated with increased inpatient mortality and cost. Respond to this article.

The mental health burden in acne vulgaris and rosacea: an analysis of the US National Inpatient Sample.

BACKGROUND: Little is known about the mental health (MH) hospitalization among patients with acne and rosacea. AIMS: To determine the MH disorders and cost burden associated with acne and rosacea. METHODS: Data were examined from the 2002-2012 US National Inpatient Sample, comprising a sample of ~20% of all US paediatric and adult hospitalizations (n = 87 053 155 admissions). RESULTS: A diagnosis of ≥ 1 MH disorder was much more common among all inpatients with vs. those without a diagnosis of acne (43.7% vs. 20.0%, respectively) and rosacea (35.1% vs. 20.0%, respectively). In multivariable logistic regression models controlling for sex, age, race/ethnicity and insurance status, acne (adjusted OR = 13.02; 95% CI 11.75-14.42) and rosacea (adjusted OR = 1.70; 95% CI 1.56-1.95) were associated with significantly higher odds of a primary admission for an MH disorder (13 and 8, respectively, of 15 MH disorders examined). Both acne and rosacea were associated with higher risk of mood, anxiety, impulse control and personality disorders, and with > $2 million of excess mean annual costs of hospitalization for MH disorders in the USA. CONCLUSION: In this study, inpatients with acne or rosacea had increased odds of comorbid MH disorders. In particular, there was an increased number of hospital admissions secondary to a primary MH disorder with coexistent acne/rosacea. MH comorbidities were associated with considerable excess costs among inpatients with acne or rosacea.

Efficacy and safety of brodalumab in patients with psoriasis who had inadequate responses to ustekinumab: subgroup analysis of two randomized phase III trials.

BACKGROUND: Brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, has demonstrated superior efficacy and safety over ustekinumab as induction therapy for moderate-to-severe psoriasis. OBJECTIVES: To evaluate the efficacy and safety of brodalumab through week 52 in patients who had inadequate responses to ustekinumab. METHODS: A subgroup analysis of the phase III AMAGINE-2/-3 double-blind randomized controlled trials was performed. Participants were aged 18-75 years and had a Psoriasis Area and Severity Index (PASI) ≥ 12, static Physician's Global Assessment score ≥ 3 and involvement of ≥ 10% body surface area. The studies were registered at ClinicalTrials.gov: AMAGINE-2, NCT01708603; AMAGINE-3, NCT01708629. RESULTS: At baseline, patients with or without prior biologic experience who had an adequate response at week 16 on ustekinumab or brodalumab had lower rates of involved body surface area, PASI, prior biologic use, psoriatic arthritis and body mass index than patients who experienced inadequate response at or after week 16. Among patients who experienced inadequate response to ustekinumab, those rescued with brodalumab had PASI ≥ 75%, ≥ 90% and 100% improvement response rates of 72·6%, 58·1% and 36·3%, respectively, at week 52 compared with 61·7%, 25·5% and 5·4%, respectively, in patients who continued ustekinumab. Exposure-adjusted rates of treatment-emergent adverse events were similar among patients rescued with brodalumab (377·3 adverse events per 100 patient-years) and those who remained on ustekinumab (389·9 adverse events per 100 patient-years). CONCLUSIONS: Among patients who experienced inadequate responses to ustekinumab, rescue with brodalumab improved skin clearance outcomes compared with continuing ustekinumab.

Role of extra oral monofocal distractor device in the correction of the facial asymmetry, sleep apnoea, and quality of life associated with TMJ ankylosis.

OBJECTIVES: The purpose of this study is to evaluate the role of primary osteo-distraction prior to ankylosis release in patients, diagnosed with sleep apnoea, facial asymmetry, and reduced quality of life secondary to temporomandibular joint (TMJ) ankylosis. METHODS: Ten patients in the age group of 13-40 years with TMJ ankylosis underwent primary osteo-distraction for mandibular advancement. They were evaluated pre- and post-operatively using radiographs, various questionnaires, and subjective evaluation of facial asymmetry, sleep apnoea, and quality of life (QOL). RESULTS: All the ten patients showed significant improvement in their sleep apnoea symptoms with a mean of 6.20 ± 1.39 (P < 0.05). The mean advancement of the mandible in all the ten patients (both bilateral and unilateral ankylosis) was 15.8 mm (P < 0.05). The quality of life showed marked improvement from very poor to very satisfactory (P < 0.001). CONCLUSION: Primary mandibular distraction is an effective method of correction of facial asymmetry, sleep apnoea, and quality of life in patients with TMJ ankylosis.

Association between hidradenitis suppurativa and hospitalization for psychiatric disorders: a cross-sectional analysis of the National Inpatient Sample.

BACKGROUND: Hidradenitis suppurativa (HS) is associated with pain, disfigurement, psychosocial distress and poor quality of life, all of which may lead to a higher likelihood of mental health (MH) disorders. However, little is known about the MH comorbidities of HS. OBJECTIVES: To determine the MH disorders and cost burden associated with HS. METHODS: Data were examined from the 2002-2012 National Inpatient Sample, comprising approximately a 20% sample of all U.S. paediatric and adult hospitalizations (87 053 155 admissions). RESULTS: MH disorders were much more common in inpatients with vs. without HS (34·27% vs. 20·05%). In multivariable logistic regression models controlling for sex, age, race/ethnicity and insurance status, HS was associated with significantly higher odds of an MH disorder (adjusted odds ratio 2·53, 95% confidence interval 2·42-2·63), including 10 of 15 MH disorders examined. In contrast, HS was not associated with primary hospitalization for an MH disorder overall (odds ratio 0·95, 95% confidence interval 0·84-1·07), but it was associated with primary hospitalization for eight of 15 MH disorders examined. Among inpatients with HS, primary admission for an MH disorder was associated with female sex, public or no insurance and more chronic diseases, but inversely associated with older age and nonwhite race/ethnicity. HS was associated with > $38 million (USD) of excess mean annual costs of hospitalization for MH disorders. CONCLUSIONS: Inpatients with HS had increased odds of comorbid MH disorders, overall, and multiple primary MH admissions, in particular, which were associated with considerable excess costs.

Association of vitiligo with hospitalization for mental health disorders in US adults.

BACKGROUND: Vitiligo has a complex bidirectional relationship with mental health (MH) disturbances. However, little is known about the relationship between vitiligo and MH emergencies. OBJECTIVE: To examine the associations of vitiligo and MH hospitalizations in the United States. METHODS: Data from the 2002 to 2012 National Inpatient Sample were analysed, including a ~20% sample of all US hospitalizations (n = 87 053 155 children and adults). Prevalence of hospitalization for MH disorders, their length of stay (LOS) and cost of care were determined for those with vitiligo compared to those without vitiligo. RESULTS: Hospitalization for MH disorders occurred more commonly in those with vitiligo compared to those without vitiligo (4.17% vs. 2.18%). In multivariable logistic regression models, vitiligo was associated with higher odds of admission for any MH disorder [adjusted odds ratio (95% confidence interval): 1.69 (1.61-1.78)], including 14 of 15 MH disorders examined. Associated MH disorders included anxiety, schizophrenia, depression, suicidal risk, personality disorder, ADD/ADHD and conduct disorder, substance use disorder, childhood and adolescent psychiatric illnesses, alcohol-related disorders, adjustment disorders, developmental disorders, impulse control disorders, history of mental health disorders and miscellaneous mental health disorders. Vitiligo patients hospitalized with any MH disorder had higher geometric-mean (95% confidence interval) cost of inpatient care [$10 992 ($10 477-$11 507) vs. $10 082 ($9728-$10 435)] and LOS [5.6 (5.3-5.8) vs. 4.8 (4.6-4.9); P < 0.0001] compared to those without vitiligo, with $10.5 million excess annual costs from hospitalization with MH disorders in persons with vitiligo. CONCLUSIONS: Persons with vitiligo had increased hospitalization for multiple MH disorders, which were associated with a considerable cost burden.

Improvement in itch and other psoriasis symptoms with brodalumab in phase 3 randomized controlled trials.

BACKGROUND: Patients with psoriasis have lesional symptoms, including itch, which can reduce quality of life. The efficacy and safety of brodalumab, an interleukin-17 receptor A antagonist, in treating moderate-to-severe psoriasis have been reported in three randomized, controlled, phase 3 trials (AMAGINE-1/-2/-3). OBJECTIVE: The effect of brodalumab on lesional symptoms was assessed using the psoriasis symptom inventory (PSI), a validated patient-reported instrument. METHODS: Patients were randomized to receive brodalumab (140 or 210 mg every 2 weeks [Q2W]), placebo (AMAGINE-1/-2/-3), or ustekinumab (AMAGINE-2/-3) during a 12-week induction phase, followed by a maintenance phase through week 52. Patients electronically rated the severity of PSI items (itch, burning, stinging, pain, redness, scaling, cracking and flaking) during the previous 24 h on a scale of 0 (not at all severe) to 4 (very severe). At each visit, the PSI total score responder status was assessed, with responders defined as having an average weekly total inventory score ≤8 with no item score >1 at week 12. RESULTS: Across AMAGINE-1/-2/-3, brodalumab was associated with improvements in PSI total scores and itch scores vs. placebo from week 2 through week 12 (P < 0.001 in both domains). In AMAGINE-2/-3, brodalumab 210 mg Q2W demonstrated faster onset of PSI total score and itch responses (week 2, 22.1% and 36.4%, respectively) vs. ustekinumab (week 2, 6.9% and 17.1%, respectively) and was associated with improved itch responses vs. ustekinumab after 52 weeks of constant treatment. CONCLUSION: Brodalumab demonstrated rapid, robust improvements in symptoms assessed by the PSI, including itch, vs. placebo and ustekinumab.

Impact of previous biologic use on the efficacy and safety of brodalumab and ustekinumab in patients with moderate-to-severe plaque psoriasis: integrated analysis of the randomized controlled trials AMAGINE-2 and AMAGINE-3.

BACKGROUND: Biologics are being used increasingly to treat moderate-to-severe psoriasis. Efficacy may differ in patients with previous exposure to biologics. OBJECTIVES: To investigate the impact of previous biologic exposure on the efficacy and safety of brodalumab and ustekinumab in patients with moderate-to-severe plaque psoriasis. METHODS: Two placebo- and ustekinumab-controlled phase III clinical trials. There was an initial 12-week induction phase where patients were treated with brodalumab [210 mg or 140 mg every 2 weeks (Q2W)], ustekinumab or placebo. Efficacy end points included ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) and static Physician's Global Assessment (score of 0 or 1) vs. placebo, PASI 100 vs. ustekinumab, Dermatology Life Quality Index and Psoriasis Symptom Inventory. Adverse events were monitored throughout. RESULTS: In total, 493 patients [334 (27%) brodalumab 210 mg Q2W and 159 (26%) ustekinumab] had received prior biologics; 150 (12%) and 62 (10%), respectively, reported previously failed treatment with a biologic. Brodalumab efficacy in patients with or without previous exposure to biologics was statistically equivalent: 40·9% and 39·5% of biologic-naive and -experienced patients achieved PASI 100 at week 12, compared with 21·1% and 17·0% with ustekinumab (both P < 0·001). In patients where prior biologics had been successful or failed, 41·7% and 32·0% achieved PASI 100, compared with 21·1% and 11·3% with ustekinumab. Tolerability was similar, and did not appear to be influenced by previous treatment with biologics. CONCLUSIONS: The efficacy of brodalumab 210 mg Q2W was similar regardless of prior biological therapy (P = 0·31, 0·32 and 0·64 for PASI 75, 90 and 100, respectively). Almost twice as many patients achieved PASI 100 or complete clearance with brodalumab at week 12 compared with ustekinumab; the differences were most noticeable where previous biologics had failed. Both treatments were well tolerated.

Small-scale screening of novel biobased monomers: the curious case of 1,3-cyclopentanediol.

In this work, we report on the small scale polycondensation and consecutive analysis of novel polyesters based on the potentially renewable 1,3-cyclopentanediol (CPdiol). To avoid evaporation of monomers during thin-film polymerization reactions, trimer pre-polyesters have been synthesized from the corresponding acid-chlorides with diol monomers. Polymerization of these trimers was explored by thermogravimetric analysis to identify potential side reactions, and to assess the ideal polymerization temperature. In general we observe that trans-1,3-cyclopentanediol exhibits good thermal stability up to 200 °C, whereas thermal dehydration of the alcohol end-groups occurs upon further heating. In contrast, for cis-1,3-cyclopentanediol, the ester bonds of the cyclopentane end-groups become labile, thereby generating carboxylic acid end-groups, and 3-cyclopentenol already at 180 °C. The thermal dehydration reactions yield double bond end-groups, which in turn facilitate cross-linking through cross-coupling and Diels-Alder reactions, leading to an increase in molecular weight. Despite the limited thermal stability of CPdiol, here we demonstrate that polymerization of CPdiol can successfully be achieved in thin-film polycondensation conditions at 180 °C, yielding molecular weights well above 10 kg mol-1.

Maternal magnesium therapy, neonatal serum magnesium concentration and immediate neonatal outcomes.

OBJECTIVE: The fetus is exposed to magnesium administered to the pregnant mother. However, there is controversy regarding magnesium-related neonatal adverse outcomes, largely driven by a limited understanding of the factors that influence neonatal serum magnesium concentrations and associated outcomes. The objective of this study was to examine the relationship between antenatal maternal magnesium dose and serum concentrations, neonatal serum magnesium concentration and immediate neonatal outcomes. STUDY DESIGN: A retrospective study was conducted at a community-based teaching hospital. Neonatal serum magnesium concentrations within 48 h of birth were used to stratify magnesium-exposed neonates into three groups: group 1: <2.5 mg dl-1, group 2: ⩾2.5 to <4.5 mg dl-1, and group 3:⩾4.5 mg dl-1. Immediate neonatal outcomes were compared between the three groups. Total maternal magnesium dose and serum magnesium concentrations before the delivery were correlated with neonatal serum magnesium concentrations and outcomes. RESULTS: Of the 304 mother-baby dyads between 24 and 34 weeks gestation, 237 received antenatal magnesium. Neonatal serum magnesium concentration was 3.14±0.83 mg dl-1 in exposed and 1.96±0.42 mg dl-1 in unexposed neonates (P<0.001). Compared with group 2, neonates had higher odds of grade 3 or 4 intraventricular hemorrhage in group 1 (adjusted odds ratio (AOR) 5.95 (95% confidence interval (CI) 1.05 to 33.66)) and group 3 (AOR 8.42 (95% CI 1.35 to 52.54)). Group 3 neonates also had increased odds of periventricular leukomalacia (AOR: 5.37 (95% CI 1.02 to 28.28) compared with group 2 neonates. Predictors of neonatal serum magnesium concentrations included maternal magnesium dose (r=0.66, P<0.0001), duration of therapy (r=0.70, P<0.0001) and serum concentration (r=0.72, P<0.001). CONCLUSION: The between-group differences highlight that there is a therapeutic range of neonatal serum magnesium concentrations for neuroprotective effects of antenatal magnesium sulfate, while concentrations outside of this range may be associated with adverse neonatal outcomes. Further studies are needed to determine the optimal dose and duration of maternal magnesium to minimize adverse neonatal outcomes.