Reduced chemokine C-C motif ligand 1 expression may negatively regulate colorectal cancer progression at liver metastatic sites.

Colorectal cancer (CRC) liver metastasis, albeit a stage-IV disease, is completely curable by surgical resection in selected patients. In addressing the molecular basics of this phenomenon, differentially expressed genes at primary and liver metastatic sites were screened by RNA sequencing with the use of paraffin-embedded surgical specimens. Chemokine C-C motif ligand 1 (CCL1), a chemotactic factor for a ligand of the chemokine C-C motif receptor 8 (CCR8), was isolated as one of the differentially expressed genes. Histological analysis revealed that the number of CCL1-positive cells, mainly tumour associated macrophages (TAMs) located in the stroma of CRC, decreased significantly at liver metastatic sites, while the expression level of CCR8 on CRC remained unchanged. To explore the biological significance of the CCL1-CCR8 axis in CRC, CCR8-positive CRC cell line Colo320DM was used to assess the effect of the CCL1-CCR8 axis on major signalling pathways, epithelial mesenchymal transition induction and cell motility. Upon stimulation of recombinant CCL1 (rCCL1), phosphorylation of AKT was observed in Colo320DM cells; on the other hand, the corresponding significant increase in MMP-2 levels demonstrated by RT-qPCR was nullified by siRNA (siCCR8). In the scratch test, rCCL1 treatment significantly increased the motility of Colo320DM cells, which was similarly nullified by siCCR8. Thus, the activation of the CCL1-CCR8 axis is a positive regulator of CRC tumour progression. Reduced CCL1 expression of TAMs at liver metastatic sites may partly explain the unique slow tumour progression of CRC, thus providing for a grace period for radical resection of metastatic lesions.

Stereoselective synthesis of D-glycero-D-manno-heptose-1ß,7-bisphosphate (HBP) from D-mannurono-2,6-lactone.

The synthesis of D-glycero-D-manno-heptose-1ß,7-bisphosphate (HBP) from D-mannose is described. This synthetic approach is notable for the elongation of the seventh carbon, employing mannurono-2,6-lactone, the substrate-controlled establishment of the C-6 configuration, and the nucleophilic introduction of phosphate at the C-1 position through the utilization of 4,6-O-benzylidene-α-triflate.

Development and validation of machine learning model for predicting treatment responders in patients with primary biliary cholangitis.

AIMS: Ursodeoxycholic acid is the first-line treatment for primary biliary cholangitis, and treatment response is one of the factors predicting the outcome. To prescribe alternative therapies, clinicians might need additional information before deciphering the treatment response to ursodeoxycholic acid, contributing to a better patient prognosis. In this study, we developed and validated machine learning (ML) algorithms to predict treatment responses using pretreatment data. METHODS: This multicenter cohort study included collecting datasets from two data samples. Data 1 included 245 patients from 18 hospitals for ML development, and was divided into (i) training and (ii) development sets. Data 2 (iii: test set) included 51 patients from our hospital for validation. An extreme gradient boosted tree predicted the treatment response in the ML model. The area under the curve was used to evaluate the efficacy of the algorithm. RESULTS: Data 1 showed that patients complying with the Paris II treatment response had significantly lower serum alkaline phosphatase and total bilirubin levels than those who did not respond. Three factors, total bilirubin, total protein, and alanine aminotransferase levels were selected as essential variables for prediction. Data 2 showed that patients complying with the Paris II criteria had significantly high prothrombin time and low total bilirubin levels. The area under the curve of extreme gradient boosted tree was good for (ii) (0.811) and (iii) (0.856). CONCLUSIONS: We demonstrated the efficacy of ML in predicting the treatment response for patients with primary biliary cholangitis. Early identification of cases requiring additional treatment with our novel ML model may improve prognosis.

Numerous multinucleated giant cells in cutaneous epithelioid angiosarcoma and pulmonary metastasis: A unique observation with potential diagnostic pitfalls.

The histopathologic diagnosis of poorly differentiated cutaneous angiosarcoma can be challenging. We report a case of cutaneous epithelioid angiosarcoma with numerous multinucleated giant cells (MGCs) developing pulmonary metastasis. A 79-year-old man presented with a red-purple plaque on the scalp. A skin biopsy revealed epithelioid cell proliferation, admixed with numerous MGCs, and background hemorrhage. Vascular spaces were focally present and lined by atypical endothelial cells, including MGCs. Immunohistochemically, tumor cells, including MGCs, were positive for CD31, D2-40, and ERG. The patient received radiation therapy and chemotherapy, after which a follow-up CT scan revealed symptomless pneumothorax and pulmonary metastases. The patient received palliative partial lung resection, and the specimen revealed histopathological and immunohistochemical features similar to the primary cutaneous lesion. Our report expands the morphologic spectrum of cutaneous epithelioid angiosarcoma. Cutaneous angiosarcoma is an aggressive neoplasm; thus, awareness of this rare manifestation is important.

Effect of postpartum depression and role of infant feeding practices on relative weight of child at 1 and 3 years of age.

BACKGROUND: Childhood obesity has increased and is considered one of the most serious public health challenges of the 21st century globally, and may be exacerbated by postpartum depression (PPD). The purpose of this study was to examine the association between PPD at 1st and 6th month postpartum, infant feeding practices, and body mass index (BMI) z-score of the child at one and three years of age. METHODS: This study used data from an ongoing prospective maternal-child birth cohort performed at the National Center for Child Health and Development (NCCHD) in suburban Tokyo, Japan with the period of recruitment from May 13, 2010 to November 28, 2013. Out of 2,309 total number of mothers, 1,279 mother-child dyads were assessed in the study. We performed multivariable linear regression analysis to examine the association between PPD and child's BMI z-score stratified by the child's age at 1 year and 3 years of age. RESULTS: The prevalence of PPD at 1 month postpartum (17%) was found to be higher than at 6 months (12%). In multivariable linear regression analysis we observed that children at 3 years who had mothers with PPD at 6 months had, on average, a BMI z-score 0.25 higher than children of mothers who did not have PPD at 6 months (ß coefficient 0.25, 95% CI [0.04 to 0.46], p value 0.02), holding all other covariates constant. Also, initiation of weaning food when child is at six months of age was associated with higher BMI z-score of the child at 3 years after adjusting for all covariates (ß coefficient = 0.18, 95% CI [0.03 to 0.34], p-value < 0.05). CONCLUSION: The significant association between PPD at 6 months and child's BMI z-score at 3 years of age, in conjunction with birth trends and high prevalence of PPD, can add to the body of evidence that there is need for multiple assessment across the first postpartum year to rule out PPD as early screening and early interventions may benefit both maternal health and child development outcomes. These findings can indicate the need for establishing support systems for care-giving activities for mothers with PPD.

Impact of the inferior vena cava morphology on fluid dynamics of the hepatic veins.

We reported previously that a large vertical interval between the hepatic segment of the inferior vena cava (IVC) and right atrium (RA), referred to as the IVC-RA gap, was associated with more intraoperative bleeding during hemi-hepatectomy. We conducted a computational fluid dynamics (CFD) study to clarify the impact of fluid dynamics resulting from morphologic variations around the liver. The subjects were 10 patients/donors with a large IVC-RA gap and 10 patients/donors with a small IVC-RA gap. Three-dimensional reconstructions of the IVC and hepatic vessels were created from CT images for the CFD study. Median pressure in the middle hepatic vein was significantly higher in the large-gap group than in the small-gap group (P = 0.008). Differences in hepatic vein pressure caused by morphologic variation in the IVC might be one of the mechanisms of intraoperative bleeding from the hepatic veins.

Prolonged warm ischemia time in the recipient is associated with post-transplant biliary stricture following living-donor liver transplantation.

PURPOSE: Post-transplant biliary stricture (PBS) is a common and important complication following orthotopic liver transplantation (LT). This study clarified the incidence of PBS and identified its risk factors. METHODS: We retrospectively reviewed the medical records of 67 patients who underwent living-donor LT (LDLT) at our institute between June 2010 and July 2022 and analyzed their clinical characteristics, prognosis, and risk factors for PBS. RESULTS: Of the 67 patients, 26 (38.8%) developed PBS during the observation period. Multivariate analyses revealed the following independent risk factors for PBS formation: increased red cell transfusion volume per body weight (> 0.2 U/kg; hazard ratio [HR], 3.8; P = 0.002), increased portal vein pressure (PVP) at the end of LT (> 16 mmHg; HR, 2.88; P = 0.032), postoperative biliary leakage (HR, 4.58; P = 0.014), and prolonged warm ischemia time (WIT) (> 48 min; HR, 4.53; P = 0.008). In patients with PBS, the cumulative incidence of becoming stent free was significantly higher in patients with a WIT ≤ 48 min than in those with a WIT > 48 min (P = 0.038). CONCLUSION: Prolonged WIT is associated with intractable PBS following LDLT.

Risk factors for cesarean section of the second twin after vaginal delivery of the first twin.

PURPOSE: To document risk factors for combined delivery, defined as unplanned cesarean section for the second twin after vaginal delivery of the first twin, particularly focusing on delivery interval between twins. METHODS: A multi-center cross-sectional study among a cohort of 5411 women with twin pregnancy experiencing vaginal delivery of the first twin in 2007-2016 at 191 tertiary referral hospitals in Japan was conducted. Primary outcome was the occurrence of combined delivery, and data were collected through the Japan Society of Obstetrics and Gynecology perinatal database. Risk factors for combined delivery were investigated using Poisson regression analysis. RESULTS: Combined delivery occurred in 235 women (5.1%) and was significantly associated with delivery interval (P < 0.001). Multivariate analysis showed women with ≥ 25 kg/m2 pre-pregnancy body mass index (BMI) and with birthweight < 1500 g of the second twin had significantly higher risk for combined delivery than women with 18.5-25 kg/m2 pre-pregnancy BMI and with birthweight ≥ 2500 g of the second twin (adjusted risk ratio (aRR) 1.72, 95% confidence interval (CI) 1.15-2.57, and aRR 2.06, 95% CI 1.14-3.72, respectively). Breech and transverse presentation of the second twin were also risk factors for combined delivery compared with cephalic presentation (aRR 3.60, 95% CI 2.67-4.85, and aRR 9.94, 95% CI 6.50-15.0, respectively). Although association of combined delivery with pre-pregnancy BMI was attenuated after adjustment by delivery interval, association with birthweight of the second twin was strengthened. CONCLUSION: Delivery interval was significantly associated with combined delivery and mediated the association between combined delivery and some other risk factors.

Similarity of oncogenic protein expression in KRASG12D gene delivery-based rat pancreatic cancer model to that of human pancreatic cancer.

BACKGROUND: The development of effective therapies and biomarkers for pancreatic cancer is an unmet clinical need. To address this, we have developed an easy-to-use pancreatic cancer rat animal model via pancreas-targeted hydrodynamic gene delivery of human pancreatic cancer-related genes. Our study aimed to determine the molecular similarity between the pancreatic tumor in the rat model and human pancreatic cancer. METHODS: KRASG12D gene-expressing plasmid was delivered to the pancreas of wild type rats via pancreas-targeted hydrodynamic gene delivery as previously reported. Tissue samples were collected at 5 weeks after the first gene delivery. The tumors developed in the rats were assessed for the expression of oncogenic proteins that are involved in human pancreatic cancer development. RESULTS: The development of a tumor mimicking pancreatic ductal adenocarcinoma was confirmed. The expression levels of Cyclin D1, c-Jun, IL-33, and Zip4 proteins in the tumor were immunohistochemically assessed and the correlation of the proteins was confirmed. The expression pattern showed similarity to that of surgically resected human pancreatic cancer tissues. CONCLUSIONS: Our study findings showing a similar pattern of oncogenic protein expression in novel KRASG12D gene-induced rat pancreatic cancer model and human pancreatic cancer will be useful for establishing novel tumor markers and therapeutic options for pancreatic cancer.

Demethylation in promoter region of severely damaged hepatocytes enhances chemokine receptor CXCR4 gene expression.

The liver is known to possess remarkable regenerative potential, but persistent inflammation or severe acute injury can lead to liver fibrosis and incomplete regeneration, ultimately resulting in liver failure. Recent studies have shown that the axis of two types of CXCL12 receptors, CXCR4 and CXCR7, plays a crucial role in liver fibrosis and regeneration. The present study aimed to investigate the regulatory factors involved in CXCR4 expression in injured liver. Immunohistochemical screening of liver tissue samples collected during liver transplantation revealed a reciprocal expression pattern between CXCR4 and MeCP2. An in vitro system involving cultured cell lines and H2O2 treatment was established to study the impact of oxidative stress on signaling pathways and epigenetic alterations that affect CXCR4 mRNA expression. Operating through distinct signaling pathways, H2O2 treatment induced a dose-dependent increase in CXCR4 expression in both hepatocyte- and intrahepatic cholangiocyte-derived cells. Treatment of the cells with trichostatin and azacytidine modulated CXCR4 expression in hepatocytes by modifying the methylation status of CpG dinucleotides located in a pair of TA repeats adjacent to the TATA box of the CXCR4 gene promoter. Only MeCP2 bound to oligonucleotides representing the TATA box region when the cytosine residues within the sequence were methylated, as revealed by electrophoretic mobility shift assay (EMSA). Methylation-specific PCR analysis of microdissected samples revealed a correlation between the loss of CpG methylation and the upregulation of CXCR4 in injured hepatocytes, replicating the findings from the in vitro study. Besides the conventional MEK/ERK and NF-κB signaling pathways that activate CXCR4 in intrahepatic cholangiocytes, the unique epigenetic modifications observed in hepatocytes might also contribute to a shift in the CXCR4-CXCR7 balance towards CXCR4, leading to irreversible liver injury and fibrosis. This study highlights the importance of epigenetic modifications in regulating CXCR4 expression in liver injury and fibrosis.

Factors, Including Clinical Trial Eligibility, Associated with Induction of Third-Line Treatment for Advanced Gastric Cancer.

INTRODUCTION: Third-line chemotherapy has been suggested to improve survival in patients with gastric cancer. This study aimed to identify factors associated with the induction of third-line chemotherapy for advanced gastric cancer, focusing on patient eligibility for clinical trial. METHODS: We retrospectively analyzed 335 patients treated for unresectable or recurrent gastric cancer between April 2009 and May 2020. The patients were grouped into those that met the key eligibility criteria for clinical trial (136 patients, 40.6%) and those that did not (199 patients, 59.4%) before receiving first-line chemotherapy. RESULTS: The overall survival (OS) was 16.8 months (95% CI: 14.0-19.6) and 9.3 months (95% CI: 7.8-11.0) in the eligible and ineligible group, respectively. Multivariate analyses to identify the risk factors associated with the induction of third-line chemotherapy revealed ineligibility of clinical trial (OR 1.95; 95% CI: 1.15-3.31), number of metastatic sites (OR 1.99; 95% CI: 1.23-3.22), low albumin concentration (OR 2.24; 95% CI: 1.14-4.38), and a lack of complete or partial response to first-line treatment (OR 1.85; 95% CI: 1.05-3.26). Indeed, in responders to first-line treatment for ineligible patients, the median OS was 17.7 months (95% CI: 10.6-27.9), respectively. CONCLUSIONS: Treatment outcomes were different for those eligible for clinical trials and those who were not. However, this study suggested that patients who responded to first-line treatment have more favorable prognosis when treated with salvage chemotherapy, even if they were deemed ineligible for clinical trials.

YAP1::MAML2 fusions in poromatosis: A report of two patients.

Poromatosis is a rare condition characterized by the development of multiple poromas, mainly reported in patients with a history of malignancy. Recently, frequent YAP1::MAML2 and YAP1::NUTM1 fusions have been described in poromas and porocarcinomas. To date, the molecular features of poromatosis have been investigated in one patient only, wherein the poromas harbored YAP1::MAML2 fusions. Herein, we present two additional cases of poromatosis with YAP1::MAML2 fusions. Case 1: An 81-year-old woman presented with nine papules on the scalp, trunk, and extremities persisting for a year. She had a history of breast cancer, with no information on the treatment. Seven papules were excised. Case 2: A 65-year-old woman presented with 21 lesions on her trunk and lower extremities persisting for 2 years. She had been diagnosed with breast cancer 11 years prior and had undergone partial mastectomy, radiotherapy, chemotherapy, and endocrine therapy. Four lesions were excised. All 11 lesions in both patients were histopathologically similar: anastomosing cords and strands extending from the epidermis, and poroid and cuticular cell proliferation with interspersed small ducts. The tumors showed diffuse nuclear expression of YAP1 N-terminus and loss of YAP1 C-terminus expression. No lesions showed NUT immunopositivity. Sanger sequencing identified YAP1::MAML2 fusions in the poromas of both patients.

Intramuscular Adipose Tissue Content as a Predictor of Incisional Hernia after Hepatic Resection.

BACKGROUND: Incisional hernia (IH) is a common surgical complication, with an incidence of 6-31% following major abdominal surgery. This study aimed to investigate the impact of intramuscular adipose tissue content (IMAC) on the incidence of IH in patients who underwent hepatic resection. METHODS: Data of 205 patients who underwent open hepatic resection between 2007 and 2019 at Ehime University Hospital were retrospectively analyzed. Patient characteristics, perioperative findings, and body composition were compared between patients with IH and those without IH. The quantity and quality of skeletal muscle, calculated as skeletal muscle index and IMAC, were evaluated using preoperative computerized tomography images. RESULTS: Forty (19.5%) patients were diagnosed with IH. The cumulative incidence rates were 15.6% at 1 year and 19.6% at 3 years. On univariate analysis, body mass index, areas of subcutaneous and visceral fat, and IMAC were significantly higher in the IH group than in the non-IH group (p = 0.0023, 0.0070, 0.0047, and 0.0080, respectively). No significant difference in skeletal muscle index was found between the groups (p = 0.3548). The incidence of diabetes mellitus, intraoperative transfusion, and postoperative wound infection was significantly higher in the IH group than in the non-IH group (p = 0.0361, 0.0078, and 0.0299, respectively). On multivariate analysis, a high IMAC and wound infection were independent risk factors for IH (adjusted odds ratio, 2.83 and 4.52, respectively; p = 0.0152 and 0.0164, respectively). CONCLUSION: IMAC can predict the incidence of IH in patients undergoing hepatic resection.

Mucosal Fixed Drug Eruption with Oral, Conjunctival, Nasal, and Anal Lesions: A Case Report.

is missing (Short communication).

Predictive factors for vaginal delivery by induction of labor in uncomplicated pregnancies at 40-41 gestational weeks: A Japanese prospective single-center cohort study.

AIM: We investigated cervical parameters predictive of vaginal delivery in elective labor induction among women at 40-41 gestational weeks. METHODS: This Japanese prospective single-center cohort study was conducted between July 2019 and June 2020. We enrolled women with an uncomplicated singleton pregnancy who underwent labor induction at 40-41 gestational weeks. We analyzed background characteristics and cervical parameters, including Bishop score, cervical length, posterior cervical angle, and changes in cervical parameters before and after cervical dilatation. The endpoint was the rate of vaginal delivery. RESULTS: Of 142 eligible participants, all 24 multiparous women underwent vaginal delivery. Among the nulliparous women (n = 118), the following categories showed significantly higher rates of vaginal delivery: Bishop scores of ≥6 before and after dilatation, compared with Bishop score <6 (adjusted prevalence ratio (aPR) [95% confidence interval (CI)]; 1.58 [1.17-2.13] and 1.56 [1.13-2.14], respectively) and cervical length of <10 and 10-20 mm before dilation, compared with cervical length of >30 mm (aPR [95% CI]; 1.47 [1.00-2.15] and 2.13 [1.42-3.18], respectively). The posterior cervical angle and other background characteristics showed no significant associations. Furthermore, women with cervical lengths of ≥20 mm before and <20 mm after dilatation showed a higher rate of vaginal delivery, compared to cervical length of ≥20 mm even after dilatation (aPR [95% CI]; 1.95 [1.19-3.20]). CONCLUSIONS: High Bishop score, short cervical length, and changes in cervical length with dilatation are potential independent predictors of vaginal delivery following elective labor induction in nulliparous women at 40-41 gestational weeks.

Predictive factors for successful external cephalic version with regional anesthesia.

AIM: We aimed to investigate predictive factors of successful external cephalic version (ECV) using regional anesthesia. METHODS: In this retrospective study, we included women who underwent ECV at our center from 2010 to 2022. The procedure had been conducted using regional anesthesia and the administration of intravenous ritodrine hydrochloride. The primary outcome was the success of ECV, which was defined as the rotation from a non-cephalic to a cephalic presentation. Primary exposures were maternal demographic factors and ultrasound findings at ECV. To determine predictive factors, we conducted a logistic regression analysis. RESULTS: Of 622 pregnant women who underwent ECV, missing data on any variables (n = 14) were excluded and the remaining 608 were analyzed. The success rate during the study period was 76.3%. Multiparous women had significantly higher success rates than primiparous women (adjusted odds ratio [OR]: 2.06 [95% confidence interval (CI): 1.31-3.25]). Women with a maximum vertical pocket (MVP) of <4 cm had significantly lower success rates than those with 4 cm < MVP ≤6 cm (OR: 0.56 [95% CI: 0.37-0.86]). The non-anterior placental location was associated with higher success rates than the anterior placental location (OR: 1.46 [95% CI: 1.00-2.17]). CONCLUSIONS: Multiparity, MVP >4 cm, and non-anterior placental locations were associated with successful ECV. These three factors could be useful for patient selection for successful ECV.

Gestational glycosuria, proteinuria, and borderline hypertension in pregnancy are predictors for the later onset of maternal chronic disease.

AIM: Although hypertensive disorders of pregnancy and gestational diabetes mellitus (DM) are risk factors for hypertension, DM, and kidney disease in later life, the association of gestational glycosuria, proteinuria, and borderline hypertension with these chronic diseases has been unclear. METHODS: This cross-sectional study was conducted between April 2017 and November 2020 at a Japanese tertiary hospital. Three variables listed in the Maternal and Child Health Handbook were analyzed: glycosuria, proteinuria, and systolic blood pressure (<130, 130-139, and ≥ 140 mmHg) during pregnancy. The incidences of DM, kidney disease, and hypertension self-reported by mothers of pregnant women on a questionnaire were assessed with logistic regression analysis. RESULTS: The 312 women completed the questionnaires an average of 35.8 ± 4.2 years after delivering their daughters. Risk for DM was significantly increased among women with glycosuria (adjusted odds ratio [aOR], 3.62; 95% confidence interval [CI], 1.21-10.9), and risk for kidney disease was significantly increased among women with proteinuria (aOR, 4.07; 95% CI, 1.29-12.9). Risk for hypertension was significant in women whose blood pressures were ≥ 140 mmHg (aOR, 4.26; 95% CI, 1.96-9.24), but the association between blood pressures of 130-139 mmHg and hypertension was not significant (aOR, 1.72; 95% CI, 0.95-3.11); however, a significant positive trend (p < 0.001) between increasing blood pressure and hypertension was observed. CONCLUSIONS: Gestational glycosuria, proteinuria, and increased blood pressure were associated with the development of maternal chronic diseases. These standard and inexpensive assessments may improve lifelong health management in women.

Association between fetal sex and pregnancy outcomes among women with twin pregnancies: a multicenter cross-sectional study.

PURPOSE: To examine the frequency and to what extent fetal sex is associated with pregnancy outcomes among twin pregnancies, stratified by chorionicity. METHODS: This registry-based multicenter cross-sectional study was conducted using the Japan Society of Obstetrics and Gynecology perinatal database between 2007 and 2016. The sample population was restricted to women with twin pregnancies. The main pregnancy-related outcomes included preterm birth, very preterm birth, extremely preterm birth, preeclampsia, twin-to-twin transfusion syndrome (TTTS), and selective intrauterine growth restriction (s-IUGR). Birth weight, small for gestational age (SGA), and fetal death were also investigated. RESULTS: The primary analysis was performed based on 37,953 women, including 23,804 women with dichorionic diamniotic (DD) twins and 14,149 women with monochorionic diamniotic (MD) twins. Women with male/male DD twins had a significantly higher risk of preterm birth (adjusted risk ratio [aRR]: 1.07, 95% confidence interval [CI]: 1.03-1.10) and a lower risk of preeclampsia (aRR: 0.74, 95% CI: 0.62-0.88) than women with female/female DD twins. Women with male/male MD twins also had a significantly higher risk of preterm birth (aRR: 1.06, 95% CI: 1.04-1.09) than women with female/female MD twins. Risks of preeclampsia, TTTS, and s-IUGR did not differ by sex among MD pregnancies. Male SGA risk was significantly higher among male/male twins than among male/female DD twins. Among MD twins, risks of SGA and fetal death were significantly higher in male/male fetuses. CONCLUSIONS: This study demonstrated significant associations between fetal sex and several pregnancy outcomes in twin pregnancies, some of which differed by chorionicity.

Monogenic causes of pigmentary mosaicism.

Pigmentary mosaicism of the Ito type, also known as hypomelanosis of Ito, is a neurocutaneous syndrome considered to be predominantly caused by somatic chromosomal mosaicism. However, a few monogenic causes of pigmentary mosaicism have been recently reported. Eleven unrelated individuals with pigmentary mosaicism (mostly hypopigmented skin) were recruited for this study. Skin punch biopsies of the probands and trio-based blood samples (from probands and both biological parents) were collected, and genomic DNA was extracted and analyzed by exome sequencing. In all patients, plausible monogenic causes were detected with somatic and germline variants identified in five and six patients, respectively. Among the somatic variants, four patients had MTOR variant (36%) and another had an RHOA variant. De novo germline variants in USP9X, TFE3, and KCNQ5 were detected in two, one, and one patients, respectively. A maternally inherited PHF6 variant was detected in one patient with hyperpigmented skin. Compound heterozygous GTF3C5 variants were highlighted as strong candidates in the remaining patient. Exome sequencing, using patients' blood and skin samples is highly recommended as the first choice for detecting causative genetic variants of pigmentary mosaicism.

Postoperative arterial lactate levels can predict postoperative pancreatic fistula following pancreaticoduodenectomy: A single cohort retrospective study.

BACKGROUND: /Objectives: Postoperative pancreatic fistula (POPF) is a serious complication after pancreaticoduodenectomy (PD). Thus, identification of the risk factors for POPF is urgently needed. In this study, we aimed to identify whether arterial lactate (LCT) levels following PD might be a marker of the potential risk of POPF. METHODS: Between September 2009 and December 2020, 151 patients who underwent elective PD were retrospectively enrolled. Patient characteristics, perioperative clinicopathological variables, postoperative blood biochemistry data were analyzed in univariable and multivariable analyses. Pancreatic fistula of Grade B and C was considered as POPF. RESULTS: Patients were divided into the POPF group (n = 33, 21.9%) and non-POPF group (n = 118, 78.1%). Higher body mass index (p = 0.017), increased estimated blood loss (p = 0.047), soft textured pancreas (p = 0.007), smaller main pancreatic duct (p = 0.016), higher LCT levels (p < 0.001), higher aspartate aminotransferase levels (p = 0.023) and higher procalcitonin levels (p = 0.024) were significantly associated with POPF. Receiver operating characteristic curve analysis revealed that 2.1 mmol/L was the optimal cut-off value of LCT (sensitivity = 78.8%, specificity = 61.2%) for predicting POPF occurrence. Univariate and multivariate analyses confirmed that an LCT of ≥2.1 mmol/L was independently associated with the risk of POPF following PD (odds ratio = 6.78, 95% confidence interval = 2.22-20.74; p = 0.001). CONCLUSIONS: Higher LCT is a predictive marker for POPF following PD.