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Abstract Introduction The pathogenesis of vascular cognitive impairment (VCI) is not fully understood. GPR39, an orphan G‐protein coupled receptor, is implicated in neurological disorders but its role in VCI is unknown. Methods We performed GPR39 immunohistochemical analysis in post mortem brain samples from mild cognitive impairment (MCI) and control subjects. DNA was analyzed for GPR39 single nucleotide polymorphisms (SNPs), and correlated with white matter hyperintensity (WMH) burden on pre mortem magnetic resonance imaging. Results GPR39 is expressed in aged human dorsolateral prefrontal cortex, localized to microglia and peri‐capillary cells resembling pericytes. GPR39–capillary colocalization, and density of GPR39‐expressing microglia was increased in aged brains compared to young. SNP distribution was equivalent between groups; however, homozygous SNP carriers were present only in the MCI group, and had higher WMH volume than wild‐type or heterozygous SNP carriers. Discussion GPR39 may play a role in aging‐related VCI, and may serve as a therapeutic target and biomarker for the risk of developing VCI.

Multicentric reticulohistiocytosis is a rare multisystem disorder of unknown etiology that is characterized by erosive polyarthritis and papulonodular lesions on the skin, mucous membranes, and internal organs. We report the case of a 54-year-old female who was misdiagnosed as having rheumatoid arthritis and underwent numerous joint replacement surgeries for progressively destructive arthritis in her hands, shoulders, hips, and knees. The patient finally received a diagnosis of multicentric reticulohistiocytosis after histopathological examination of the patient’s left knee arthroplasty which revealed a diffuse histiocytic infiltrate, multinucleated giant cells, and finely granulated eosinophilic cytoplasm with a ground-glass appearance.

Dysregulated lysophosphatidic acid receptor 1 (LPAR1) signaling is implicated in fibrotic diseases, including systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF). Fipaxalparant (HZN-825) is a small molecule acting as a negative allosteric modulator of LPAR1 and is in phase 2 clinical evaluations for treating diffuse cutaneous SSc and IPF. This open-label, phase 1 study examined the pharmacokinetics (PKs), food effect, and safety of fipaxalparant in healthy volunteers. Dose proportionality was evaluated for fipaxalparant single doses of 150, 300, and 450 mg under fasted conditions. Food effect was tested with a 450-mg single dose under fasted conditions or with a high-fat meal. Multiple-dose PKs for twice-daily dosing of either 300 or 450 mg with low- or high-fat meals was also assessed. Fipaxalparant was safe and well tolerated in healthy volunteers (n = 36) under all conditions. Fipaxalparant exposure increased in a less than dose-proportional manner from 150 to 450 mg. At 450 mg, a high-fat meal increased the maximum observed concentration and area under the curve by approximately 1.9- and 2.1-fold, respectively. These results, combined with prior preclinical and phase 2a data, informed dose selection of fipaxalparant 300 mg once and twice daily with a meal for phase 2b studies., (© 2024 The Authors. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

Background: The first-line treatment for most giant cell tumors (GCTs) of bone is surgical; radiotherapy (RT) is reserved for inoperable or refractory cases. While RT techniques have undergone a dramatic change over the past few decades, with the higher energy megavoltage RT replacing orthovoltage RT, concerns for high rates of malignant transformation following RT have limited its use. Evidence suggests a lower incidence of secondary malignancy after treatment with megavoltage compared with orthovoltage RT, but this has not been studied in GCTs. Our main purpose was to compare the incidence of malignant transformation of GCTB between patients treated with orthovoltage vs. megavoltage RT., Methods: A literature review was performed to identify studies reporting GCTBs treated with RT from 01/1900 through 12/2019. Studies that did not report RT modality or separate orthovoltage and megavoltage results were excluded. Included in the analysis were 6 patients from our institution. Primary outcome was the incidence of malignant transformation; secondary outcomes were time to transformation and incidence of local recurrence. Fisher's exact tests and independent sample t -tests were used, and significance was set at p < 0.05., Results: Twenty-two studies were included, which reported on 168 GCTBs treated with orthovoltage and 393 treated with megavoltage RT. Transformation incidence was 14% ( n  = 24) for orthovoltage and 1.8% ( n  = 7) for megavoltage RT, an 8-fold difference (odds ratio (OR) 9.1, 95% confidence interval (CI) 3.9-22, p < 0.001). Mean time to transformation was 8.7 years for orthovoltage and 11.2 years for megavoltage RT ( p =0.28). Incidence of local recurrence was 38% (63/167) for orthovoltage and 17% (66/393) for megavoltage RT (OR 3.3, 95% CI 2.0-4.6, p < 0.001)., Conclusions: The risk of developing a malignancy after RT of GCTB is 8 times lower with megavoltage than with orthovoltage. Malignant transformation with megavoltage, while not zero, is lower than that in historical series. Use of modern RT techniques in inoperable or refractory GCTB may be appropriate., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Farah N. Musharbash et al.)

Background . Idiopathic thrombocytopenic purpura (ITP) is a bleeding disorder in which the immune system destroys native platelets. In this condition an autoantibody is generated against a platelet antigen. ITP affects women more often than men and is more common in children than adults. Objective . To assess the effect of Helicobacter pylori eradication therapy (HPET) on platelet count in Helicobacter pylori associated chronic immune thrombocytopenic purpura (chronic ITP) in adult. Materials and Methods . It is an interventional prospective study conducted at Liaquat University of Medical and Health Sciences, Jamshoro, from 2014 to 2015. A set of 85 patients diagnosed with chronic ITP were included in the study via convenient sampling. Patients with platelets count < 100 × 10 9 /L for >3 months were selected. They were posed to first-line investigations which comprised complete blood count (CBC) and peripheral blood smear examination followed by second-line tests including bone marrow examination and Helicobacter pylori stool specific antigen (HpSA-EIA). Standard H. pylori eradication therapy was offered and the patients were assessed at regular intervals for 6 months. Results. Of the 85 study patients, 32 (37.6%) were male and 53 (62.3%) were female. Mean ages of H. pylori positive and negative subjects were 43.89 ± 7.06 and 44.75 ± 7.91 years, respectively. Bone marrow examination confirmed the diagnosis and excluded other related BM disorders. H. pylori stool antigen (HpSA) was detected in 34 (40%) patients and hence regarded as H. pylori positive; the rest were negative. Treatment with eradication therapy significantly improved the mean platelet counts from 48.56 ± 21.7 × 10 9 /l to 94.2 ± 26.8 × 10 9 /l. Conclusion. We concluded that the anti-H. pylori eradication therapy improves blood platelet counts in chronic immune thrombocytopenia., Competing Interests: The authors declare that they have no competing interests.

Objective: To review induction of labor analyzed by body mass index (BMI) category in primigravidas and multigravidas., Design: Prospective observational study., Population: Women enrolled after sonographic confirmation of singleton pregnancy in the first trimester., Setting: Large university teaching hospital., Methods: Maternal height and weight were measured accurately before BMI calculation. Clinical details were recorded after review of individual obstetric records., Main Outcome Measures: Emergency cesarean section and obstetric interventions., Results: Of 2000 women enrolled, 50.4% (n = 1008) were primigravidas and 17.3% (n = 346) were obese. The induction rate was 25.6% and the overall cesarean section rate 22.0%. Primigravidas were more likely to have labor induced than multigravidas (38.1% vs. 23.4%, p < 0.001). Compared with women with a normal BMI, obese primigravidas but not obese multigravidas were more likely to have labor induced. In primigravidas who had labor induced, the cesarean section rate was 20.6% (91/442) compared with 8.3% (17/206) in multigravidas who had labor induced (p < 0.001). In obese primigravidas, induction of labor was also more likely to be associated with other interventions such as epidural analgesia, fetal blood sampling and emergency cesarean section. In contrast, induction of labor in obese multigravidas was not only less common but also not associated with an increase in other interventions compared with multigravidas with a normal BMI., Conclusions: Due to the short-term and long-term implications of an unsuccessful induction in an obese primigravida, we recommend that induction of labor should only be undertaken for strict obstetric indications after careful consideration by an experienced clinician., (© 2013 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: The aim of this study was to profile longitudinal changes in thigh muscle and fat with gestation and to determine whether thigh measurements can improve the prediction of birth weight (BW)., Methods: A prospective longitudinal study of subcutaneous soft tissue measurements was conducted in 328 singleton fetuses at 28 and 37 weeks gestation. Estimated fetal weight (EFW) was calculated using abdominal circumference, femur length, biparietal diameter, and head circumference., Results: The fetal abdominal subcutaneous tissue (FAST) and thigh muscle and fat show an increase with gestation. At 28 weeks gestation, the abdominal circumference, thigh fat, FAST, and EFW percentile were found to be significant predictors of BW. A combination of EFW percentile and thigh fat were found to be the optimal multivariate model at 28 weeks for predicting BW. At 37 weeks, BW prediction using EFW percentile, FAST, and thigh fat was the most accurate. The results revealed acceptable reproducibility for fetal thigh muscle and fat., Conclusion: This study provides reference ranges for thigh fat and muscle at 28 and 37 weeks gestation. The inclusion of fetal thigh fat in the algorithm improves the predictive power for birth weight. This information is important to explore the role of fetal thigh in the detection of aberrant growth., (© 2013 John Wiley & Sons, Ltd.)

Objective: The aims of the study were to establish reference ranges for placental length and thickness in a low-risk obstetric population and to assess the likelihood of a small for gestational age (SGA) neonate on the basis of placental length at 18-24 weeks' gestation., Methods: Placental length and thickness were measured by two sonographers in 520 singleton pregnancies. Uterine artery Doppler studies and a placental morphological assessment were also performed. Placental size was correlated with the birthweight centiles at delivery., Results: A placental length <10th centile between the gestational age of 18 and 24 weeks is a significant factor associated with SGA neonate [odds ratio (OR) = 2.8, 95% CL, 1.1-6.9]. An abnormal uterine artery Doppler is a significant factor for SGA neonate (OR = 3.4, 95% CL, 1.6-7.4). There was a weak relationship between cord insertion <2 cm from the placental margin and an SGA neonate (OR = 1.8, 95% CL, 0.4-8.2)., Conclusion: We have provided reference ranges for placental length and thickness from 18 to 24 weeks' gestation. A single measurement of placental length incorporated into the anatomy scan may assist in the early detection of a group at risk of delivering an SGA neonate., (© 2012 John Wiley & Sons, Ltd.)

Objective: We evaluated screening with a diagnostic oral glucose tolerance test earlier than 20 weeks gestation in women with moderate to severe obesity., Design: Prospective observational study., Setting: Large university teaching hospital., Population: We enrolled 100 women booking for antenatal care in the first trimester at their convenience., Methods: Height and weight were measured and body mass index calculated. Only women with a body mass index > 34.9 kg/m(2) were included. Women were booked for a 100 g oral glucose tolerance test before 20 weeks and, if normal, another test at 28 weeks gestation., Main Outcome Measures: Impaired glucose tolerance and gestational diabetes mellitus., Results: Of the 100 women given an appointment for an oral glucose tolerance test before 20 weeks gestation, 92 attended. Of these, 10 (10.8%) women had an abnormal result, with impaired glucose tolerance in five (5.4%) cases and gestational diabetes mellitus in five (5.4%) cases. Of those with a normal result at 20 weeks, 81 attended for a repeat test at 28 weeks gestation. A further four (4.9%) had impaired glucose tolerance and four (4.9%) had gestational diabetes mellitus. A total of 18 (20.5%) of the 88 women who complied with screening had an abnormal test., Conclusions: Women who have moderate/severe obesity have a one in five chance of having an abnormal diagnostic oral glucose tolerance test when screened for gestational diabetes mellitus. To optimize maternal glycemic control in pregnancy, we suggest that women with a body mass index > 34.9 kg/m(2) may need to be screened early in pregnancy and, if the test is normal, again at 28 weeks gestation., (© 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2012 Nordic Federation of Societies of Obstetrics and Gynecology.)

A retrospective cohort study was carried out in a university teaching hospital to determine the prospective risk of unexpected fetal death in uncomplicated monochorionic diamniotic (MCDA) twin pregnancies after viability. All MCDA twins delivered at or after 24 weeks' gestation from July 1999 to July 2007 were included. Pregnancies with twin-twin transfusion syndrome, growth restriction, structural abnormalities, or twin reversed arterial perfusion sequence were excluded. Of the 144 MCDA twin pregnancies included in our analysis, the risk of intrauterine death was 4.9%. The prospective risk of unexpected intrauterine death was 1 in 43 after 32 weeks' gestation and 1 in 37 after 34 weeks' gestation. Our results demonstrate that despite close surveillance, the unexpected intrauterine death rate in uncomplicated MCDA twin pregnancies is high. This rate seems to increase after 34 weeks' gestation, suggesting that a policy of elective preterm delivery warrants evaluation., (© 2011 The Authors Acta Obstetricia et Gynecologica Scandinavica © 2011 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: To review maternal mortality in a large stand-alone maternity hospital in a European city and to determine whether the increased cesarean rate was associated with an increase in maternal deaths., Methods: The details of maternal deaths at Coombe Women and Infants University Hospital, Dublin, Ireland, as published in the hospital's Annual Clinical Reports for 1995-2009, were reviewed. Maternal mortality ratio was defined as the number of maternal deaths per 100,000 live births., Results: Over 15 years, 112,326 women delivered 114 170 infants weighing at least 500 g. The cesarean rate increased from 14.1% in 1995 to 26.5% in 2009 (20.0% overall). The maternal mortality ratio was low at 2.7 per 100 000 live births. There were 2 maternal deaths following cesarean, neither of which was attributable to the operation., Conclusion: In Ireland, a large stand-alone maternity hospital can achieve a low maternal mortality ratio, according to international standards, despite an increase in cesarean rate over the past 2 decades. There was no evidence that the increased cesarean rate had an adverse impact on maternal mortality ratio., (Copyright © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Objective: Previous studies on weight gain in pregnancy suggested that maternal weight on average increased by 0.5-2.0 kg in the first trimester of pregnancy. This study examined whether mean maternal weight or body composition changes in the first trimester of pregnancy., Design: Prospective observational study., Population: We studied 1,000 Caucasian women booking for antenatal care in the first trimester of pregnancy., Setting: Large university teaching hospital., Methods: Maternal height and weight were measured digitally in a standardized way and Body Mass Index (BMI) was calculated. Maternal body composition was measured using segmental multifrequency Bioelectrical Impedance Analysis (BIA). Sonographic examination confirmed the gestational age and a normal ongoing singleton pregnancy in all subjects., Main Outcome Measures: Maternal weight, maternal body composition., Results: The mean BMI was 25.7 kg/m(2) and 19.0% of the women were in the obese category (> or =30.0 kg/m(2)). Cross-sectional analysis by gestational age showed that there was no change in mean maternal weight, BMI, total body water, fat mass, fat-free mass or bone mass before 14 weeks gestation., Conclusions: Contrary to previous reports, mean maternal weight and mean body composition values remain unchanged in the first trimester of pregnancy. This has implications for guidelines on maternal weight gain during pregnancy. We also recommend that calculation of BMI in pregnancy and gestational weight gain should be based on accurate early pregnancy measurements, and not on self-reported or prepregnancy measurements.