Umbilical Level Research Articles

Elevated Expression of ADAMTS-12 in Maternal and Umbilical Cord Serum of Placenta Accreta Spectrum

Objective We investigated a disintegrin and metalloproteinase with thrombospondin type 1 motif-12 (ADAMTS-12) levels in both fetal umbilical cord and maternal blood of pairs diagnosed with placenta accreta spectrum (PAS). Method We analyzed ADAMTS-12 level by ELISA in 160 samples that included 30 control pairs (30 maternal and 30 umbilical cord serums), 20 pairs in the placenta previa (PP), and 30 pairs in the PAS group (30 maternal and 30 umbilical cord serums). Results There were increased serum levels of ADAMTS-12 in maternal serum (p = 0.037) and umbilical cord serum level (p = 0.004) of PAS group compared with the PP and healthy control groups. There was a positive correlation between maternal ADAMTS-12 and fetal ADAMTS-12 serum levels (r = 0.53, p = 0.002). Conclusion Our findings indicate that ADAMTS-12 could be a ­diagnostic biomarker for PAS.

Indicator of thyroid hormones in newborns from mothers with diffuse-endemic goiter

Introduction. Pathologies of thyroid dysfunction associated with iodine deficiency remain one of the urgent problems throughout the world and are mainly associated with natural iodine deficiency in places where about 30% of the world’s population lives.Objective. Study of the dynamics of thyroid hormones in infants born from mothers with diffuse endemic goiter.Materials and methods. A retrospective study of 68 infants from mothers with diffuse endemic goiter (DEG) was carried out. Research methods included: analysis of anamnestic data, palpation, and ultrasound in mothers, with a study of the level of thyroid hormone in newborns and parturient women.Results. Infants from mothers with DEG have characteristic changes in the level of thyroid hormones in the blood, in particular, in the cord blood, the level of thyroid-stimulating hormone (TSH) is 22.4% higher than in the control group (p < 0.05). The difference between free triiodothyronine (T3) and thyroxine (T4) is on average lower by 8.6% and 4.3%, respectively, (p < 0.05 and p < 0.1). On the 3rd day of life, these fluctuations persist, and the level of TSH in the peripheral blood exceeded up to 20.9%, but there were no pronounced clinical signs of congenital pathology associated with the thyroid gland. At the same time, in the first months of life in infants, there is a lag in weight gain by an average of 9.6% about practically healthy newborns.Conclusion. In infants born to mothers with DEG, there is an increase in the umbilical blood level of TSH up to 22.4% about practically healthy newborns, with a simultaneous decrease in T4 to 4.3%, T3 to 8.6%, without pronounced clinical signs of congenital pathology. In these children, in the first months of life, there is a lag in physiological weight gain of up to 9.6%, which should be taken into account when managing children in an outpatient setting.

Comparison between the modified French AmbUlatory Cesarean Section and standard cesarean technique—a randomized double-blind controlled trial

The French AmbUlatory Cesarean Section is a cesarean delivery technique, which includes a vertical fascial incision to the left of the linea alba and an extraperitoneal approach to the uterus. The presumed benefits of this technique are decreased postoperative pain and accelerated recovery. However, evidence supporting these impressions is scarce. This study aimed to compare maternal recovery after French AmbUlatory Cesarean Section vs standard cesarean delivery technique. In this double-blind randomized controlled trial, women undergoing elective cesarean delivery at term were allocated into French AmbUlatory Cesarean Section vs standard cesarean delivery technique. A modified French AmbUlatory Cesarean Section technique was used, adhering to all French AmbUlatory Cesarean Section operative steps except for the extraperitoneal approach. In both groups, the use of intravenous hydration, intrathecal morphine, and bladder catheter was avoided, and all women were encouraged to stand and walk 3 to 4 hours after the operation. The primary adverse composite outcome included either of the following: a visual analog scale score of >6 at 3 to 4 hours after the operation, an inability to stand up and walk to the restroom 3 to 4 hours after the operation, and a 15-Item Quality of Recovery (QoR) questionnaire score of <90 at 24 hours after the operation. The women were followed up for 6 weeks. Overall, 116 women were included in the trial (58 in each group). The adverse composite outcome did not differ between the 2 groups (38.9% for the French AmbUlatory Cesarean Section group vs 53.8% for the regular cesarean delivery group; P=.172). In both groups, more than 90% of the women were able to get up and walk 3 to 4 hours after the operation. Compared with the standard cesarean delivery group, the French AmbUlatory Cesarean Section group had a longer duration of the operation (43.7±11.2 vs 54.4±11.3 minutes; P<.001), a higher rate of intraoperative complications (0.0% vs 13.8%; P=.006), and a higher rate of umbilical cord pH level of <7.2 (3.4% vs 17.2%; P=.029) were noted. Evaluation via phone call 1 week after the operation showed better quality of recovery scores in the French AmbUlatory Cesarean Section group than in the standard cesarean delivery group (27.1±8.4 vs 24.6±8.0; P=.043). Other secondary outcomes did not differ between the 2 groups. As excellent maternal recovery was noted in both groups, we believe that the main factor affecting this recovery is the perioperative management (including avoidance of the use of intraoperative intravenous hydration, intrathecal morphine, and bladder catheter, with early postoperative mobilization). The maternal and neonatal safety outcomes of the French AmbUlatory Cesarean Section technique remain to be proven by larger-scale high-quality randomized controlled trials.

Incidence of and Risk Factors for Neonatal Hypothyroidism Among Women with Graves' Disease Treated with Antithyroid Drugs Until Delivery.

Background: The incidence of neonatal hypothyroidism among newborns born to mothers with Graves' disease (GD) who continued antithyroid drug (ATD) treatment until delivery has never been reported. Objective: Our primary objective was to investigate the incidence of neonatal hypothyroidism among newborns born to mothers with GD who were treated with ATD until delivery. Our secondary objective was to identify the cutoff ATD daily doses for neonatal hypothyroidism risk, based on maternal thyrotropin (TSH) receptor antibody (TRAb) levels. Methods: We conducted a retrospective cohort study. We included 305 pregnant women with GD who were treated with an ATD until delivery (63 treated with methimazole [MMI] and 242 treated with propylthiouracil [PTU]). Umbilical cord TSH, free thyroxine (fT4), and TRAb levels were measured at delivery, and we investigated the respective relationships between neonatal hypothyroidism at delivery and maternal fT4 levels, TRAb levels, and daily ATD doses during pregnancy. Neonatal hypothyroidism was diagnosed when the umbilical cord fT4 level was below the lower limit of the reference range. Results: The incidence of neonatal hypothyroidism at delivery was 19.0% ([confidence interval, CI, 11.2-30.4]; 12/63) in the MMI group and 12.8% ([CI, 9.2-17.6]; 31/242) in the PTU group. Neonatal goiter was observed in one neonate in the PTU group, and two infants in the PTU group required levothyroxine treatment. The daily ATD dose in the third trimester was the strongest predictor of neonatal hypothyroidism at delivery; the cutoff MMI dose was 10 mg/day, and the cutoff PTU dose was 150 mg/day. When the maternal TRAb level in the third trimester was above three times the upper limit of the normal range, the cutoff MMI dose was 20 mg/day, and the cutoff PTU dose was 150 mg/day. Conclusions: Maternal fT4 and TRAb levels were higher in the neonatal hypothyroid group, which suggested prolonged GD activity. Careful follow-up is necessary when maternal GD remains active and the ATD dose to control maternal thyrotoxicosis cannot be reduced.

Excess visceral fat area as an independent risk factor for early postoperative complications in patients with obesity undergoing bariatric surgery.

Few studies have investigated the correlation between visceral fat area (VFA) and early postoperative complications in patients with obesity undergoing bariatric surgery. This study aimed to investigate the relationship between VFA and early postoperative complications in patients with obesity following bariatric surgery. The study was conducted at a tertiary university hospital. Patients with obesity who underwent laparoscopic sleeve gastrectomy between June 2016 and October 2020 were divided into two groups based on umbilical level VFA: high-VFA group (umbilical level VFA ≥ 100 cm2) and low-VFA group (umbilical level VFA < 100 cm2). Baseline characteristics, intraoperative and postoperative conditions, and early postoperative complications were compared between the groups. The primary outcome was early postoperative complications, and the secondary outcome was postoperative hospital stay. The study included 152 patients, with 82 patients in the low-VFA group and 70 patients in the high-VFA group. The high-VFA group had a higher incidence of early postoperative complications (14.29% vs. 2.44%, P = 0.013) than the low-VFA group. The length of postoperative hospital stay did not differ significantly between the groups. Our study suggests that excess VFA is an independent risk factor for early postoperative complications following bariatric surgery, and VFA may be used in preoperative evaluations.

Umbilical cord serum insulin-like growth factor-1 levels of infants of diabetic mothers are correlated with diastolic dysfunction detected by tissue Doppler echocardiography.

To our knowledge, this is the first study to examine the relationship between cord serum IGF-1 levels and diastolic functions of IDMs assessed by TDI. A weak correlation was found between IGF-1 levels and IVS and LVPW thicknesses in M-Mode and LV e' and LV e'/a' parameters in TDI, revealing diastolic dysfunction in IDMs. • The umbilical cord blood serum IGF-1 level of IDMs is higher than in infants of healthy mothers. • Diastolic dysfunction is a well-studied and frequently observed consequence in IDMs. • This is the first study to examine the relationship between cord serum IGF-1 levels and diastolic functions of IDMs assessed by TDI. • A weak correlation was detected between the median cord serum IGF-1 level of IDMs and the median values of IVS, LVPW, LV e', LV a', LV e'/a' ratio.

S-44-5: RELATIONS OF AGE, VISCERAL FAT AREA, HOMA-R, AND LIFESTYLE HABITS WITH HYPERTENSION IN THE COMPREHENSIVE HEALTH CHECKUP PROGRAM

Objective: Relations of visceral fat with hypertension (HT) have been reported in both Caucasians and in Asians. However, few studies have examined each systolic and diastolic blood pressure (BP) in detail. We investigated the relations of BP status with various metabolic parameters, including visceral fat area (VFA), subcutaneous fat area (SFA), insulin resistance index HOMA-R and lifestyle habits in participants in our health checkup program. Design and method: Cross-sectional study. A total of 3,480 male and 2,467 female subjects, aged 16–93 years (median: 59 years), who participated in the comprehensive health checkup program at our University Hospital, were enrolled in this study. Informed consent was obtained from each subject, and subjects who met the predetermined exclusion criteria or were on treatment for diabetes mellitus (DM) were excluded from the analyses. We divided participants into 4 groups according to BP status criteria: normotensive (NT), high normal (HN), HT, and HT with medication (HT+Tx). We used low-energy computed tomography to measure VFA, SFA, and waist circumference at the umbilical level. Results: Participants aged 50–70 years in the HN, HT, and HT+Tx groups had significantly higher mean VFAs compared with subjects in the NT group (P &lt; 0.0001 for both gender). Exercise habit was not related with HT status in either gender. In univariate and multivariate analyses, systolic BP was correlated with age, VFA, and HOMA-R, and diastolic BP was correlated with VFA, family history (FH) of HT, and alcohol intake (&gt; 20 g/day). Furthermore, multiple logistic regression analyses (including HT+Tx group) with HT as a dependent variable revealed that age, FH of HT, VFA, HOMA-R, and alcohol intake were relevant (Table, P &lt; 0.0001). Conclusions: These results from our comprehensive health checkup program suggest that age, FH of HT, VFA, HOMA-R, and alcohol intake are independently related to HT status.

Sarcopenia and excess visceral fat accumulation negatively affect early urinary function after I-125 low-dose-rate brachytherapy for localized prostate cancer.

To evaluate the effects of sarcopenia and excess visceral fat accumulation on early urinary function after I-125 low-dose-rate brachytherapy for prostate cancer. We retrospectively reviewed consecutive patients who underwent brachytherapy for prostate cancer. Pre-treatment computed tomography was used to measure skeletal muscle index at the L3 level to assess sarcopenia and visceral fat area at the umbilical level. The International Prostate Symptom Score and the University of California Los Angeles Prostate Cancer Index were used to assess quality of life during the 24months after brachytherapy. Logistic regression analysis was used to examine whether sarcopenia and excess visceral fat accumulation had clinically significant effects on post-treatment quality of life. Among 246 patients, 92 (37.4%) were stratified into the sarcopenia group and 141 (57.3%) into the excess visceral fat accumulation group. The sarcopenia group had significantly lower University of California Los Angeles Prostate Cancer Index urinary function than the non-sarcopenia group 24months post-brachytherapy. The excess visceral fat accumulation group had significantly poorer International Prostate Symptom Score total, storage, and voiding scores than the non-excess accumulation group 12months post-brachytherapy. In the multivariate analysis, sarcopenia had a clinically significant adverse effect on the University of California Los Angeles Prostate Cancer Index urinary function at 12months. Excess visceral fat accumulation had a clinically significant adverse effect on the International Prostate Symptom Score voiding and storage scores at 12months. Sarcopenia and excess visceral fat accumulation negatively affect urinary function early after I-125 low-dose-rate brachytherapy for prostate cancer.

A case report of multiple Mycobacterium Kansasii bone infection with pathological fracture of T11 vertebral body and thoracic spinal cord injury

Rationale: Cases of vertebral infection with bone destruction and spinal cord injury caused by Mycobacterium kansasii infection are rarely reported, and the infection is usually associated with severe immunosuppression. Patient concerns: A 62-year-old male patient was hospitalized for 10 days due to recurrent low back pain with diminished skin sensation below the umbilical level. Diagnosis: The patient had no underlying disease. MRI showed multiple bone destruction lesions throughout the body, pathological fractures of the T11 vertebral body, and compression and degeneration of the thoracic spinal cord. Complete back abscess puncture examination, CT-guided vertebral puncture examination, metagenomic next-generation sequencing and bone marrow puncture and other examinations to confirm the diagnosis of Mycobacterium kansasii infection. Intervention: According to the drug susceptibility test of pathogenic bacteria, combined antiinfective treatment was given. After 3 weeks of drug treatment, the patient underwent thoracic posterior debridement, spinal canal decompression, and pedicle screw internal fixation. Outcome: The skin sensation of the patient’s lower limbs was improved 1 month after the operation compared with that before the operation. After adhering to oral drug treatment, the inflammatory index decreased steadily. Four months after the operation, the skin sensation of the patient’s lower extremities returned to normal. Lessons: Regular, adequate, and full course of drug treatment is the key to the treatment of Mycobacterium kansasii infection. Next-generation metagenomic sequencing can improve the efficiency and accuracy of the detection of Mycobacterium kansasii. For patients with abscesses and spinal nerve compression, surgical decompression and abscess removal are effective treatment options.

Umbilical cord blood interleukin-6 level as a predictor of early-onset neonatal sepsis

&#x0D; &#x0D; Background Neonatal sepsis is a global health problem contributing significantly to neonatal morbidity and mortality. It is difficult to clinically distinguish neonates with and without sepsis. Interleukin-6 (IL-6) concentration in neonates has high sensitivity and specificity to predict neonatal sepsis in infants at risk.&#x0D; Objective To determine the utility of umbilical cord blood IL-6 as a predictor of early-onset neonatal sepsis.&#x0D; Methods This prospective cohort study was conducted in neonates born to mothers with sepsis risk factors from December 2020 to January 2021. We measured IL-6 from umbilical cord blood taken after placental expulsion. IL-6 ³16.4 pg/ml was considered to be elevated. Subjects were monitored for signs of clinical sepsis until 72 hours after birth. We also recorded the presence of other maternal and infant risk factors of sepsis and assessed association between IL-6 and other risk factors with the occurrence of sepsis, expressed as relative risk (RR) with 95% confidence interval (95%CI).&#x0D; Results During the study period, 40 neonates were born to mothers with sepsis risk factors; 13 (32.5%) developed clinical sepsis. Significantly more infants with elevated IL-6 developed neonatal sepsis (55.5%) than those with normal IL-6 (13.6%). After multivariate analysis incorporating other significant variables, the risk factors predictive of clinical early-onset neonatal sepsis were IL-6 [RR 5.54 (95%CI 1.68-18.25); P=0.016], prematurity [RR 4.92 (95%CI 1.66-14.59); P=0.014], and initial Apgar score [RR 3.38 (95%CI 1.34-3.38); P=0.046].&#x0D; Conclusion In neonates with maternal risk factors, an IL-6 level of ³16.4 pg/ml is associated with an increased risk of early-onset neonatal sepsis.

V-004 REDO ETEP APPROACH FOR SMALL BOWEL INCARCERATION DUE TO POSTERIOR SHEATH SEPARATION: AN UNUSUAL COMPLICATION

Abstract Aims The retromuscular-preperitoneal approach of primary or incisional hernias is a technique that is being performed more frequently due to the more anatomical position of the mesh, the lower rates of complications and recurrences in the short and long term.However, this technique is not without complications, the most frequent being retromuscular seromas or hematomas, the rarest being incarcerated hernias secondary to dehiscence of the posterior sheath closure,hence the importance of presenting this case. Methods Video-case presentation. Results 40-year-old man with surgical histories:open appendectomy 20years-ago, and endoscopic repair(eTEP-Rives) of umbilical hernia and diastasis of the rectus abdominis. He went to the emergency room 4days after surgery(eTEP) due to sudden, intense abdominal pain, located in the mesogastrium.Abdominal-CT:hernial defect at the umbilical level (posterior-sheath-dehiscence) with incarcerated and dilated small-bowel inside. We decided to perform urgent surgical intervention.An iterative eTEP-retromuscular-laparoscopic-approach was performed,observing hernial defect due to dehiscence of the posterior-sheath suture at the umbilical level with incarcerated small bowel loops within the retromuscular space.Hernia content revision and reduction is performed, previous mesh is removed and since tension is visualized for the closure of the hernial defect, right Hemi-TAR is performed, after which a tension-free closure of the the posterior sheath, and PVDF-mesh is placed.The patient presented a satisfactory evolution. Conclusions The enhanced view totally-extraperitoneal-approach(eTEP) is a valid, effective and safe option in cases of acute complications,such as the one presented,through which more complex separation techniques(TAR) can be associated to achieve a correct and tension-free closure of the abdominal wall, presenting the advantages of MIS.

P-095 RECTUS DIASTASIS REPAIR: VARIATIONS OF POSTPARTUM ABDOMINAL WALL ANATOMICAL CHANGES PROPOSE A TAILORED SURGICAL REPAIR. EARLY RESULTS OF THE EXTENDED REPAIR TECHNIQUE STUDY

Abstract Aim A pregnancy can result in permanent anatomical changes such as a persistent rectus diastasis (RD), a widened linea semilunaris and retracted oblique muscles. The diverse anatomical changes contribute to the abdominal deformation and may present in a variety of combinations. A standardized suture repair of the RD may not be sufficient in severe abdominal wall deformation cases. This observational cohort study evaluated an extended repair technique. Method A cohort of 44 postpartum women with training resistant core instability symptoms planned for surgical repair were examined with ultrasonography prior to surgery. Participants with severe anatomical changes i.e. diastasis of the linea semilunaris exceeding one cm, were offered an extended repair, re-approximation of both linea alba and linea semilunaris. Results were evaluated with ultrasonography and the Disability Rating Index (DRI), two and twelve months after surgery. A standardized rectus diastasis suture repair was used in 24 participants with an isolated rectus diastasis. A combined repair with reapproximation of both the linea alba and the linea semilunaris was performed in 20 participants. Results Preoperative mean rectus diastasis (widest measurement) was 45 mm (30–75 mm), a mean diastasis of the linea semilunaris (umbilical level) of 15 mm (0–35 mm). There were no recurrencies at the 12-month follow-up. Early results showed significant improvements of physical function (DRI) but no differences between the two repair technique groups. Conclusion The extended repair seems to be a safe and sufficient repair technique in cases with a RD combined with a linea semilunaris diastasis.

Placental and Umbilical Cord Blood Oxidative Stress Level and Telomere Homeostasis in Early Onset Severe Preeclampsia.

Although the etiopathogenesis of preeclampsia (PE) is unknown, evidence suggests that it may be associated with increased oxidative stress. Studies have shown that oxidative stress can affect DNA fragments called telomeres. However, the interactions of PE, oxidative stress, and telomere length are not clearly known. This study aims to evaluate the oxidative/anti-oxidative stress balance in the placenta and umbilical cord and examine the effect of oxidative stress on telomeres. Cord blood and placental samples were collected from 27 pregnant women with severe PE (280/7-336/7 gestational weeks) and 53 healthy pregnant women. Telomere length (TL) was measured by real-time PCR in the cord blood and placenta tissue. Total antioxidant status (TAS) and total oxidant status (TOS) levels were measured in the cord blood and placenta tissue using a colorimetric method. No significant differences were found between groups regarding age, BMI, gravida, parity, and newborn gender (p>0.05). Cord blood and placental TL of PE patients were significantly shorter than the control group, while cord blood and placental TAS and TOS levels were higher (p<0.05). The results of a multivariate logistic regression analysis showed that the level of placental TOS in PE patients (OR=1.212, 95% CI=1.068-1.375) was an independent risk factor affecting PE. This study found that oxidative stress is an independent risk factor in the development of PE and shortens TL in both placental and umbilical cord blood. Future research on telomere homeostasis may offer a new perspective for the treatment of PE.

Minimally Invasive Tensiometry: A New Modality for Per-Operative Measurement of Medialization and Tension During Laparoscopic Hernia Surgery.

Background: Newly developed techniques for minimally invasive abdominal wall reconstruction (AWR) for complex ventral hernia are continuously evolving. In order to achieve hernia defect closure, the aponeurotic edges of the hernia defect need to be approximated. Currently, surgeons have no way to objectively measure and quantify the traction required to approximate these edges. This study presents minimally invasive tensiometry (MINT), a novel technology for measuring fascial tension, as well as initial experiences and results using it. Methods: The MINT device was designed using rapid prototyping principles. It was designed as an add-on tool for any existing laparoscopic instrument, enabling objective assessment of abdominal wall tension by the use of a manually operated linear spring. Pre-clinical measurements of medialization at 10 and 20N of tension during AWR were performed on fresh-frozen Post-Mortem Human Specimens (PMHS). Results: Three specimens were included, and a total number of 36 measurements of medialization at three different levels of the abdominal wall were performed under structured and similar circumstances. Median total medialization with 20 Newton (N) of applied tension was 25 mm (mm) cranially, 37.5mm at the umbilicus and 27.5mm at the caudal level. The highest rate of medialization was seen at the umbilical level (2.25mm/N). Conclusion: MINT is a novel non-invasive technique, which allows surgeons to intraoperatively measure fascial tension when performing AWR. The MINT device is easy to use and reproduce. The next step is to start performing clinical measurements applying MINT during AWR.

The Optimal Axial Anatomical Site for a Single-Slice Area to Quantify the Total Volume of Visceral Adipose Tissue in Quantitative CT.

PurposeDetermine the association between cross-sectional visceral adipose tissue (VAT) area of different anatomic locations and total abdominopelvic VAT volume; identify the optimal measurement site in a single-slice to quantify the total VAT volume.MethodParticipants who underwent non-contrast abdominal scan by quantitative CT (QCT) were enrolled from May 2021 to October 2021. The VAT area (cm2) at different anatomic sites as upper-pole, lower-pole, and hilum of the kidney, intervertebral disc of L2/L3 and L5/S1, and umbilical level were measured on QCT PRO BMD workstation (Mindways QCT PRO workstation). The total VAT volume (cm3) from the upper pole of kidney to the L5/S1 intervertebral disc of the pelvis (abdominopelvic region) was obtained by using Siemens Healthineers Syngo via Frontier cardiac risk assessment. Regression models were used to identify the optimal single-slice in different gender for estimating VAT volume. Statistical significance was established at P < 0.05.ResultsTotal of 311 Chinese participants including 179 men [age, 55.1 ± 14.9 years; body mass index (BMI), 24.2 ± 3.2 kg/m2; total VAT volume, 2482.6 ± 1276.5 mL] and 132 women [age, 54.3 ± 14.9; BMI, 23.5 ± 2.9; total VAT volume, 1761.5 ± 876.4]. Pearson’s correlation analysis revealed a strong association between the VAT area and total abdominopelvic VAT volume at the hilum of the kidney in both men (r=0.938, P<0.001) and women (r=0.916, P<0.001). Adjust for covariates including age, BMI, and waist circumference make a relatively small effect on predicting the total VAT volume.ConclusionsMeasurement of cross-sectional areas at the hilum of the kidney in both genders showed a strongest relation to TVAT volume. Our results may provide an identifiable and valuable axial landmark for measuring visceral adipose tissue in clinical practice.

Intramuscular Adipose Tissue Content Predicts Patient Outcomes after Allogeneic Hematopoietic Stem Cell Transplantation

During clinical courses involving treatment with allogeneic hematopoietic stem cell transplantation (allo-HSCT), multidisciplinary patient assessment including physical function is indispensable, and quantitative skeletal muscle loss is a poor prognostic marker. Deteriorating quality of muscle from intramuscular adipose tissue degeneration can be important as well, because many patients are cachexic or sarcopenic before allo-HSCT, although this approach has not yet been used in such patients. We conducted this retrospective cohort study to evaluate the quality as well as quantity of skeletal muscle using computed tomography (CT) scans. The psoas muscle mass index (PMI) and radiographic density (RD) calculated by cross-sectional area and averaged CT values of the psoas major muscle at the umbilical level were used to determine the quantity and quality of muscle, respectively. A total of 186 adult patients, ranging in age from 17 to 68 years (median, 49 years), were included in this study, with 46 (24.7%) assigned to the lower PMI group and 49 (26.3%) assigned to the lower RD group. Low RD was identified as an independent risk factor for poor overall survival after allo-HSCT (adjusted hazard ratio [HR], 2.54; P < .01), whereas PMI was not significant. Decreased RD along with a reduced 6-min walking distance before transplantation were significant factors in increased nonrelapse mortality (HR, 2.69; P = .01). This study is the first to suggest the use of a qualitative skeletal muscle index to serve as a prognostic indicator following allo-HSCT. RD should be included in pretransplantation screening parameters, and approaches that include rehabilitation focused on improving both muscle quality and quantity may improve the prognosis of allo-HSCT.

Factors associated with the progression of myosteatosis in patients with cirrhosis

ObjectivesThe presence of myosteatosis is one factor associated with poor prognosis for patients with cirrhosis; however, the factors contributing to worsening myosteatosis are, to our knowledge, unknown. The aim of this study was to clarify the changes in myosteatosis, and the factors involved in these changes. MethodsThe present study enrolled 178 patients with cirrhosis who underwent computed tomography twice to measure changes in skeletal muscle attenuation (SMA) at the L3 level. Factors associated with SMA and those associated with changes in SMA were examined. ResultsUsing linear multiple regression analysis, age (β = –0.22), skeletal muscle index (SMI; skeletal muscle area divided by height squared; β = 0.25), and visceral and subcutaneous fat indices (VFI and SFI; the visceral and subcutaneous fat areas at the umbilical level divided by height squared; β = –0.08, β = –0.06, respectively) were identified as associated with SMA. The 100-d change in SMA was –0.21 ± 1.29 Hounsfield units (HU). Changes in SMI and SMA were positively associated (R = 0.183, P = 0.014), whereas those in VFI and SMA were negatively associated (R = –0.172, P = 0.022). No association was noted between the 100-d changes in SFI and SMA. In patients whose SMI increased and VFI decreased, the 100-d change in SMA was 0.24 ± 1.82 HU, which was marginally different from that in patients whose SMI decreased and VFI increased (–0.44 ± 1.32 HU, P = 0.077). ConclusionsIn patients with cirrhosis, myosteatosis progressed, and decreases in SMI and increases in VFI were correlated with its progression.

Application of a Physiologically Based Pharmacokinetic Approach to Predict Theophylline Pharmacokinetics Using Virtual Non-Pregnant, Pregnant, Fetal, Breast-Feeding, and Neonatal Populations.

Perinatal pharmacology is influenced by a myriad of physiological variables that are changing dynamically. The influence of these covariates has not been assessed systemically. The objective of this work was to use theophylline as a model drug and to predict its pharmacokinetics before, during (including prediction of the umbilical cord level), and after pregnancy as well as in milk (after single and multiple doses) and in neonates using a physiological-based pharmacokinetic (PBPK) model. Neonatal theophylline exposure from milk consumption was projected in both normal term and preterm subjects. Predicted infant daily doses were calculated using theophylline average and maximum concentration in the milk as well as an estimate of milk consumption. Predicted concentrations and parameters from the PBPK model were compared to the observed data. PBPK predicted theophylline concentrations in non-pregnant and pregnant populations at different gestational weeks were within 2-fold of the observations and the observed concentrations fell within the 5th−95th prediction interval from the PBPK simulations. The PBPK model predicted an average cord-to-maternal plasma ratio of 1.0, which also agrees well with experimental observations. Predicted postpartum theophylline concentration profiles in milk were also in good agreement with observations with a predicted milk-to-plasma ratio of 0.68. For an infant of 2 kg consuming 150 ml of milk per day, the lactation model predicted a relative infant dose (RID) of 12 and 17% using predicted average (Cavg,ss) and maximum (Cmax,ss) concentration in milk at steady state. The maximum RID of 17% corresponds to an absolute infant daily dose of 1.4 ± 0.5 mg/kg/day. This dose, when administered as 0.233 mg/kg every 4 h, to resemble breastfeeding frequency, resulted in plasma concentrations as high as 3.9 (1.9–6.8) mg/L and 2.8 (1.3–5.3) (5th−95th percentiles) on day 7 in preterm (32 GW) and full-term neonatal populations.

Disentangling Litter Size and Farrowing Duration Effects on Piglet Stillbirth, Acid-Base Blood Parameters and Pre-Weaning Mortality.

The current study evaluated interactions between farrowing duration and litter size on the level of asphyxia, vitality, percentage of stillbirth, and pre-weaning mortality of piglets. Farrowing duration was measured in 159 crossbred gilts and sows (Yorkshire × Dutch Landrace). Litter size ranged between 12 and 21 piglets. Blood acid–base parameters in umbilical cord blood and vitality scores of piglets were determined immediately after birth. Number of piglets born alive and stillborn as well as individual piglet weights at birth were recorded. Pre-weaning mortality (excluding stillbirth) was determined throughout lactation. Litter size as well as farrowing duration were categorized to evaluate the interaction between the two. There tended to be an interaction between litter size and farrowing duration for pre-weaning mortality (p = 0.10). In small litters (12–15 piglets), a prolonged farrowing duration (>250 min) tended to increase pre-weaning mortality compared with a short (<150 min) and medium farrowing duration (150–250 min), while for large litters (19–21 piglets), a medium to long farrowing duration tended to decrease pre-weaning mortality. No other interactions between litter size and farrowing duration were found. Piglets within large litters showed a higher umbilical cord lactate level (p < 0.01), lower average vitality score (p = 0.01), and a higher stillborn percentage (p < 0.01) compared with piglets within medium size (16–18 piglets) and small litters. Each additional piglet born to a litter linearly decreased average piglet birth weight (17.6 g, p < 0.01), increased farrowing duration (11 min, p < 0.01), and increased stillbirth (0.5%, p = 0.04). A medium farrowing duration resulted in a lower stillborn percentage compared with a short or prolonged farrowing duration, suggesting that farrowing duration might have an optimum. When analyzed linearly, stillborn percentage increased with 1.85% per every 100 min (p < 0.01) of farrowing duration. It can be concluded that both litter size and farrowing duration affect stillborn percentage, but independent from each other. However, these two factors tended to interact regarding pre-weaning mortality, suggesting that setting a certain threshold for maximal farrowing duration should be taken with care, because this appears to depend on litter size.

Subcutaneous adipose tissue is a positive predictor for bone mineral density in prepubertal children with Prader-Willi syndrome independent of lean mass.

Emerging evidence suggests a fat depot-specific relationship with bone mineral density (BMD) in children, particularly in those who are overweight/obese. However, this has not yet been investigated in detail in children with Prader-Willi syndrome (PWS), a genetic syndrome characterized by a decreased lean mass (LM) and increased fat mass (FM). The objective of this study is to investigate the relationships of LM and FM, particularly fat distribution, with bone mineral parameters. This is a retrospective and cross-sectional study. Forty-seven prepubertal Japanese children with PWS (22males, mean age: 6.86 years) were included. No subjects had type 2 diabetes mellitus or osteoporotic medications. LM, FM, and BMD and bone mineral content in the total body less head and the lumbar spine were measured using dual-energy x-ray absorptiometry, in addition to subcutaneous/visceral adipose tissue (SAT/VAT), and the ratio of VAT to SAT (V/S) by computed tomography at the umbilical level. Bone mineral apparent density was calculated to correct for bone size. LM positively correlated with bone mineral parameters after controlling for age, sex, growth hormone (GH) treatment, and FM. Although FM did not correlate with bone mineral parameters, compartment-specific analysis revealed that SAT positively and V/S negatively correlated with bone mineral parameters after controlling for age, sex, GH treatment and LM. A compartment-specific effect of FM on bone mineral parameters was noted such that SAT was a positive predictor for BMD independent of LM in prepubertal children with PWS.