SIRT1 promotes chemoradiotherapy resistance in esophageal squamous cell carcinoma.

Introduction Identifying accurate biomarkers for predicting response to chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC) is a critical challenge. The protein SIRT1, recognized for its implications in longevity, has been associated with tumor promotion in ESCC. However, data regarding its correlation with CRT sensitivity remains unreported. Therefore, in this study, we aimed to investigate the relationship between SIRT1 expression and CRT sensitivity and concurrently assess the effect of SIRT1 knockdown on CRT sensitivity in ESCC. Methods This study included 73 patients who underwent radical esophagectomy after CRT. SIRT1 expression in pre-treatment endoscopic biopsies was assessed through immunostaining, followed by a comparative analysis of CRT effects on surgical specimens. Small interfering RNA was used to attenuate SIRT1 expression in TE5 and TE10 cells, which were then subjected to cisplatin treatment at varying doses and concentrations and irradiation with X-rays, respectively. Results High SIRT1 tissue expression was significantly associated with CRT resistance. Multivariate analysis identified high SIRT1 expression as an independent biomarker for poor CRT response. In TE-5 and TE-10 cells, SIRT1 knockdown significantly decreased cell viability and increased sensitivity to cisplatin and radiation treatment compared to that of the negative control. Conclusion Our study results demonstrate the potential of SIRT1 as a predictive biomarker for CRT response in ESCC, highlighting the heightened sensitivity to CRT upon the transcriptional inactivation of SIRT1. Targeting SIRT1 emerges as a promising strategy for enhancing the efficacy of CRT for ESCC.

Establishment of a novel small bowel adenocarcinoma cell line using patient­derived xenografts, which produces CEA and CA19­9.

Small bowel adenocarcinoma (SBA) is a rare tumor with a poor prognosis. Due to its rarity, the research infrastructure for SBA, including cell lines, is inadequate. The present study established a novel SBA cell line, SiCry-15X, using patient-derived xenografts of SBA. The following criteria were defined for establishment: Long-term culturability, tumorigenicity and similarity with the original tumor. The biological characteristics of the cell line, its sensitivity to anticancer drugs and its ability to produce tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were evaluated. SiCry-15X cells adhered and grew as a monolayer, with a population doubling time of 37 h. Polymerase chain reaction results confirmed the human origin of the cell line, and short tandem repeat analysis revealed that the cells were genetically identical to the original tumor. The 50% inhibitory concentrations of 5-fluorouracil, paclitaxel, irinotecan, oxaliplatin and cisplatin for SiCry-15X were 104.05, 0.24, 63.3, 146.55 and 49.29 µM, respectively. CEA and CA19-9 concentrations in the culture media were markedly elevated. In addition, CEA and CA19-9 levels in the serum of cell-derived xenograft model mice were elevated. Moreover, CEA and CA19-9 were produced by SiCry-15X cells and distributed throughout the blood. Furthermore, increases in serum CEA and CA19-9 of cell-derived xenograft model mice were consistent with the clinical course of the disease. The newly established SBA cell line, SiCry-15X, could be an effective tool for conducting further studies on SBA.

Hypoxia­regulated exosomal miR­185 inhibits esophageal squamous cell carcinoma progression and predicts prognosis.

Despite advances in treatment and diagnosis, the prognosis of patients with esophageal squamous cell carcinoma (ESCC) remains poor. MicroRNAs (miRNAs/miRs) are associated with prognosis in esophageal cancer, indicating that they may help guide treatment decisions. The aim of the present study was to explore exosomal miR-185 as a candidate prognostic biomarker and therapeutic target in ESCC, to investigate its biological function and clinical significance, and to ascertain the applicability of circulating exosomal miR-185 for the development of targeted drugs for ESCC treatment. A GeneChip miRNA array was used to compare exosomal miRNA expression in ESCC cell lines under hypoxia with those under normoxia. Exosomal miR-185 expression was then confirmed by reverse transcription-quantitative PCR. Patient background and prognosis were compared between high and low miR-185 expression groups. Functional analyses were performed to evaluate the antitumor effects of miR-185 in ESCC cells. Global Gene Set Enrichment Analysis of The Cancer Genome Atlas data was also performed, and differentially expressed exosomal miRNAs under hypoxia were identified compared to those under normoxia. Hypoxia markedly decreased the expression of exosomal miR-185 in KYSE-960 and T.Tn cell culture media. Overexpression of miR-185 suppressed the migration, invasion and colony-forming abilities of ESCC lines, and also suppressed cell cycle progression and promoted apoptosis after cisplatin treatment. Notably, high miR-185 expression was associated with signaling pathways related to cell death, DNA damage and p53. Furthermore, circulating exosomal miR-185 levels were associated with cN and cStage, and could predict progression-free survival and disease-specific survival of patients with ESCC after initial treatment. In conclusion, miR-185 holds potential as a prognostic biomarker and therapeutic target in ESCC.

A case of laparoscopic revision surgery 30 years after vertical banded gastroplasty for morbid obesity.

As the number of bariatric and metabolic surgeries being performed is increasing, the importance of revision surgeries is escalating. In this report, we describe a case of revision surgery performed 30 years after vertical banded gastroplasty (VBG), including a review of the surgical techniques. The patient was a male in his 50s who had previously undergone VBG for morbid obesity (body mass index of 72.6 kg/m2 ), resulting in gradual weight loss. Twenty-eight years later, reflux symptoms due to stenosis of the mesh area developed. Despite conservative treatment, the symptoms recurred, and aspiration pneumonia developed. Gastrojejunal and Y-anastomoses were performed laparoscopically. Postoperatively, the patient progressed well with no weight regain. In revision surgery, it is essential to accurately assess the patient's pathophysiology, as the surgical technique must consider improvement in symptoms, risk of weight regain, and the need for observation of the residual stomach.

Soluble PD­L1 reflects cachexia status in patients with gastric cancer and is an independent prognostic marker for relapse­free survival after radical surgery.

Soluble programmed death-ligand 1 (sPD-L1) levels can be used as a biomarker for gastric cancer (GC). However, comprehensive information regarding the sPD-L1 expression profiles and their association with cachexia in GC is lacking. Therefore, the present study evaluated the association between clinicopathological findings and sPD-L1 levels in patients with GC. Serum samples were collected from patients with GC during their first visit to Department of Esophageal-Gastro-Intestinal Surgery, Chiba University Hospital, Chiba, Japan (January 2012-December 2017; n=173), and sPD-L1 levels were measured using an enzyme-linked immunosorbent assay. Survival rates among 116 patients, excluding cases with preoperative chemotherapy or no radical procedures, were analyzed. sPD-L1 levels were associated with factors such as neutrophil-to-lymphocyte ratio, hemoglobin (Hb) and albumin (Alb) levels, total cholesterol and C-reactive protein (CRP) levels, and related to inflammation and nutrition in patients. Notably, the higher the number of applicable indicators related to cachexia (Hb <12 g/dl, Alb <3.2 g/dl, CRP >0.5 mg/dl and low body mass index) was, the higher the sPD-L1 value was. However, the pathological stage did not significantly differ between the groups. Clinicopathologically, there was no association with tumor depth, lymph node metastasis or vascular invasion; however, patients with the intestinal type had significantly higher sPD-L1 levels than patients with the diffuse type (P=0.032; Wilcoxon test). The overall survival did not significantly differ between the groups with low and high sPD-L1 levels; however, among patients who received radical treatment, the relapse-free survival was significantly worse in the high-sPD-L1-level group than in the low-sPD-L1-level group (P=0.025; log-rank test). Multivariate Cox regression analysis revealed that a high sPD-L1 concentration was a sign of poor prognosis, independent of pathological stage and cancer antigen CA19-9 (P=0.0029). Therefore, the present findings suggest that sPD-L1 can reflect cachexia status in patients with GC and may serve as a prognostic marker for relapse-free survival after radical GC surgery.

Gut microbiome can predict chemoradiotherapy efficacy in patients with esophageal squamous cell carcinoma.

PURPOSE: The gut microbiome plays an important role in cancer pathogenesis and therapy. Some studies have reported that specific bacteria in tumor tissues may contribute to the prognosis and treatment of esophageal squamous cell carcinoma (ESCC). However, there is limited evidence that the gut microbiome is associated with ESCC. This study assessed the utility of the gut microbiome as a predictive marker of the therapeutic effect in patients with ESCC undergoing chemo-radiotherapy (CRT). PATIENTS AND METHODS: Fecal samples were collected from 51 patients with ESCC who had never undergone treatment between April 2021 and May 2022 in the Department of Frontier Surgery, Chiba University. The gut microbiome was analyzed using 16S metagenomics sequencing. The association between the gut microbiome composition and stage according to the TNM classification (American Joint Committee on Cancer 7.0) and CRT response according to the RECIST criteria was evaluated. RESULTS: The relative abundance of Fusobacteriaceae was enriched in cStage III-IVb group. Among the 27 patients who received CRT, the relative abundance of Lactobacillaceae was enriched in those with a partial and complete response. Lactobacillaceae also did not correlate with any clinical data, but the high Lactobacillales group had a higher LMR (P = 0.032) and lower PLR (P = 0.045) than in the low Lactobacillales group. CONCLUSIONS: In conclusion, we found that the relative abundance of Lactobacillaceae was enriched in patients with a partial or complete response among CRT those with ESCC, thus suggesting that the relative abundance of Lactobacillaceae can predict the effect of CRT.

Serum Versus Tissue SIRT1 as Potentially Valuable Biomarkers in Gastric Cancer.

BACKGROUND/AIM: We lack reports on the clinicopathological characteristics and prognostic value of serum sirtuin 1 (SIRT1) levels and their association with SIRT1 expression in tissues of patients with gastric cancer (GC). Thus, we investigated the pathological characteristics and prognostic values of SIRT1 tissue expression and its serum concentration in GC. Moreover, we investigated the correlation between these two factors. MATERIALS AND METHODS: A total of 78 patients with GC who underwent curative gastrectomy were evaluated in this study. The expression of SIRT1 in the surgical specimens was assessed using immunohistochemistry. Serum levels of SIRT1 were measured using an enzyme-linked immunosorbent assay. The association of tissue and serum SIRT1 with the clinicopathological features and prognosis were evaluated. RESULTS: Positive SIRT1 tissue expression was significantly related to an advanced cancer stage (p=0.017). Furthermore, a significant relationship existed between a positive SIRT1 tissue expression and poorer overall survival (OS) and relapse-free survival (RFS) (p=0.033 and p=0.033, respectively). In contrast, serum SIRT1 levels showed no significant association with clinicopathological characteristics besides age. In addition, no significant correlation was observed between tissue SIRT1 expression and serum SIRT1 concentration. CONCLUSION: Tissue SIRT1 expression may be a valuable novel prognostic biomarker; nonetheless, further studies are required to clarify the relationship between tissue SIRT1 expression and serum SIRT1 levels in GC.

Standard versus low-dose nab-paclitaxel in previously treated patients with advanced non-small cell lung cancer: A randomized phase II trial (JMTO LC14-01).

BACKGROUND: Nab-paclitaxel (nab-PTX) has better transfer to tumor tissue than cremophor-based paclitaxel. It suggests that the optimum dose of nab-PTX might be lower than the dose and schedule that is widely used. We designed a randomized phase II trial to examine the clinical utility and safety of nab-PTX in patients with previously treated advanced non-small cell lung cancer (NSCLC). METHODS: Patients were randomly allocated (1:1) to receive nab-PTX monotherapy at 100 mg/m2 (group A) or 70 mg/m2 (group B). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), and adverse events (AEs). RESULTS: Finally, 81 patients were randomized. Similar results were observed in both groups for PFS (3.75 vs. 3.71 months), OS (13.50 vs. 16.13 months), or ORR (20.5% vs. 23.1%). The incidences of grade 3 or worse AEs were 57.5% in group A and 41.5% in group B. The proportion of serious side effects was 10.0% in group A and 4.9% in group B. CONCLUSION: Both standard dose and low dose of nab-PTX monotherapy are active for previously treated NSCLC patients with better safety profile. Therefore, nab-PTX 70 mg/m2 dose and schedule in the trial would be a reasonable option.

Transition from epoprostenol to selexipag in a patient with systemic sclerosis and pulmonary hypertension during the postoperative period of colon cancer surgery: A case report.

Introduction: Most pulmonary vasodilators are administered orally; however, in patients with pulmonary hypertension undergoing gastrointestinal surgery, a switch to parenteral drugs is needed. Parenteral pulmonary vasodilators carry a risk of infection and reduced quality of life owing to long-term central venous catheterization; therefore, it is preferable to switch them to oral vasodilators after surgery. Here, we present the case of a patient with systemic sclerosis complicated by pulmonary hypertension and colon cancer, for which treatment was successfully switched from epoprostenol to selexipag postoperatively. Case Description: A 59-year-old woman, who was diagnosed with mixed group I and III pulmonary hypertension and systemic sclerosis, was on oral triple pulmonary vasodilators for pulmonary hypertension and Raynaud's phenomenon. She was diagnosed as having colon cancer 3 months before admission. Despite the severe pulmonary condition and treatment with oral triple pulmonary vasodilators, colon cancer resection surgery was performed with the management for pulmonary hypertension through multidisciplinary treatments in collaboration with cardiology specialists. Medications for patients with pulmonary hypertension undergoing gastrointestinal surgery need to be switched from oral vasodilators to epoprostenol perioperatively. On postoperative day 19, 0.4 mg/day of selexipag was administered with epoprostenol. Subsequently, the epoprostenol dosage was gradually decreased, and selexipag was increased. On postoperative day 30, the dose of selexipag was increased to 1.2 mg/day and epoprostenol was discontinued. The patient was discharged on postoperative day 40. Conclusion: In our case, transition from epoprostenol to selexipag contributed to a more useful management strategy for systemic sclerosis and pulmonary hypertension in the postoperative period.

Chest computer tomography is safe without additional interrogation or monitoring for modern cardiac implantable electrical devices.

INTRODUCTION: Whether diagnostic computed tomography (CT) scans to cardiac implantable electronic devices (CIED) is safe in recent models remains unknown. METHODS: A two-centers observational study. Over 14 years, consecutive 2362 chest CT scans (1666 pacemakers [PMs], 145 cardiac resynchronization therapy PM, 316 implantable cardioverter-defibrillator, and 233 cardiac resynchronization therapy defibrillator) were interrogated and monitored upon imaging. RESULTS: Electromagnetic interference occurred only in a few old models: InSync 8040 (n = 14), InSync III Marquis (n = 1), and Kappa (n = 4), which resulted no adverse events. CONCLUSION: CIEDs, especially recent ones, are confirmed safe on chest CT.

HbA1c level may be a risk factor for oxygen therapy requirement in patients with coronavirus disease 2019.

INTRODUCTION: Many clinical studies have identified significant predictors or risk factors for the severity or mortality of coronavirus disease 2019 (COVID-19) cases. However, there are very limited reports on the risk factors for requiring oxygen therapy during hospitalization. In particular, we sought to investigate whether plasma glucose and HbA1c levels could be risk factors for oxygen therapy requirement. MATERIALS AND METHODS: A single-center, retrospective study was conducted of 131 COVID-19 patients hospitalized at Saitama Medical University Hospital between March 2020 and November 2020. To identify the risk factors for oxygen therapy requirement during hospitalization, a stepwise multivariate binary logistic regression analysis was performed using several clinical parameters commonly obtained on admission, including plasma glucose and HbA1c levels. RESULTS: Of the 131 patients with COVID-19, 33.6% (44/131) received oxygen therapy during hospitalization. According to the logistic regression analysis, male sex (odds ratio [OR]: 8.76, 95% confidence interval [CI]: 1.65-46.5, P < 0.05), age (OR: 1.07, 95% CI: 1.02-1.12, P < 0.01), HbA1c levels (OR: 1.94, 95% CI: 1.09-3.44, P < 0.05), and serum C-reactive protein (CRP) levels (OR: 2.22, 95% CI: 1.54-3.20, P < 0.01) emerged as independent variables associated with oxygen therapy requirement during hospitalization. CONCLUSIONS: In addition to male sex, age, and serum CRP levels, HbA1c levels on admission may serve as a risk factor for oxygen therapy requirement during the clinical course of COVID-19, irrespective of diabetes history and status. This may contribute to the efficient delegation of limited numbers of hospital beds to patients at risk for oxygen therapy requirement.

Clinical features resembling subcutaneous insulin resistance observed in a patient with type 2 diabetes and severe COVID-19-associated pneumonia: a case report.

We report the case of a 52-year-old hyperglycemic woman with type 2 diabetes and severe coronavirus disease 2019 (COVID-19)-associated pneumonia, possibly involving the subcutaneous insulin resistance (SIR) syndrome. After admission for pneumonia, her average daily blood glucose (BG) levels remained at 300-400 mg/dL, although the required dosage of subcutaneous insulin markedly increased (~ 150 units/day; ~ 2.63 units/kg/day). Furthermore, the patient had generalized edema along with hypoalbuminemia, developed extensive abdominal purpuras, and had increased plasma D-dimer levels during treatment, suggestive of coagulation abnormalities. Therefore, intravenous infusion of regular insulin was initiated. The BG level subsequently decreased to < 200 mg/dL 2 days after administering 18 units/day of insulin infusion and 118 units/day of subcutaneous insulin, suggesting that subcutaneous insulin alone might have been ineffective in reducing hyperglycemia, which is clinically consistent with the characteristics of an SIR syndrome. Impaired skin microcirculation arising from coagulation abnormalities, subcutaneous edema associated with inflammation-related hypoalbuminemia or vascular hyperpermeability, and/or reduction in subcutaneous blood flow due to COVID-19-induced downregulation of angiotensin-converting enzyme 2 might be associated with the development of pathological conditions that resemble SIR syndrome, leading to impaired subcutaneous insulin absorption. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-021-00500-x.

Differences in the birthweight of infants born to patients with early- or mid-to-late-detected gestational diabetes mellitus who underwent guideline-based glycemic control.

AIMS: To examine the effects of strict glycemic control on the birthweight of infants born to Japanese patients with early- or mid-to-late-detected gestational diabetes mellitus (ed- or md-GDM). METHODS: We retrospectively examined the characteristics of 101 patients with GDM who underwent guideline-based glycemic control. A 75-g oral glucose tolerance test was conducted to diagnose GDM at gestational weeks 11-15 (ed-GDM subgroup) and 24-28 (md-GDM subgroup). RESULTS: Infant birthweight was significantly lower in the ed-GDM subgroup (n = 25) than in the md-GDM subgroup (n = 76) (2688.3 ±â€¯470.4 g vs. 3052.4 ±â€¯383.1 g, p < 0.05), and the proportion of low-birthweight infants (<2500 g) was significantly higher in the ed-GDM subgroup than in the md-GDM subgroup (32.0% vs. 5.3%, p < 0.005). Fasting plasma glucose (FPG) levels during early treatment and before delivery were significantly lower in the ed-GDM subgroup than in the md-GDM subgroup (76.1 ±â€¯10.4 mg/dL vs. 85.5 ±â€¯9.6 mg/dL, p < 0.001; 80.5 ±â€¯10.4 mg/dL vs. 90.4 ±â€¯10.3 mg/dL, p < 0.0001). CONCLUSIONS: Patients with ed-GDM showed significantly lower FPG levels during treatment compared to those with md-GDM, presumably indicating an association with the delivery of low-birthweight infants.

Effects of dapagliflozin on renin-angiotensin-aldosterone system under renin-angiotensin system inhibitor administration.

Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) are reported to prevent cardiovascular events by a mechanism possibly including diuresis and sodium excretion. In this respect, diuresis-induced compensatory upregulation of the renin-angiotensin-aldosterone (RAA) system should be clarified and we performed a randomized controlled trial using dapagliflozin, an SGLT2I. Hypertensive diabetic patients taking angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers were randomly assigned to a dapagliflozin group (DAPA) or a control group (CTRL) with the difference in the changes in plasma renin activity (PRA) after 24 weeks of the treatment as the primary outcome. PRA, plasma aldosterone concentration (PAC), age, sex, BMI, blood pressure, pulse rate, eGFRcys, and HbA1c were not different between the groups at baseline. After 24 weeks, the changes in the PRA from the baseline of the DAPA (n = 44) and CTRL (n = 39) groups were 6.30 ± 15.55 and 1.42 ± 11.43 ng/mL/h, respectively (p = 0.11) although the power of detection was too small. However, post hoc nonparametric analyses revealed that there was a definite increase in the PRA and PAC in the DAPA group (p < 0.0001 and p = 0.00025, respectively) but not in the CTRL group. The PRA in the DAPA group after 24 weeks treatment was significantly elevated compared to the CTRL group (p = 0.013) but not for the PAC. Accordingly, it would be suggested that dapagliflozin may not induce a profound increase, if any, in PAC after 24 weeks of treatment in hypertensive type 2 diabetic patients under RAA suppression.

Production of styrene oxide from styrene by a recombinant Escherichia coli with enhanced AcrAB-TolC efflux pump level in an aqueous-organic solvent two-phase system.

The AcrAB-TolC efflux pump is involved in the organic solvent tolerance of Escherichia coli. Most E. coli strains are highly sensitive to organic solvents such as n-hexane and cyclohexane. Here, a recombinant E. coli transformed with an expression plasmid containing acrAB and tolC became tolerant to n-hexane and cyclohexane. The levels of AcrA, AcrB, and TolC in the recombinant increased by 3- to 5-fold compared to those in the control strain without the plasmid for acrAB or tolC. To investigate the usability of the recombinant as a biocatalyst in an aqueous-organic solvent two-phase system, we further introduced xylMA xylene monooxygenase genes from Pseudomonas putida mt-2 into the recombinant and examined the production of styrene oxide from styrene. The resulting recombinant produced 1.8 mg and 1.0 mg styrene oxide mL-1 of medium in a medium overlaid with a 25% volume of n-hexane and cyclohexane containing 10% (wt vol-1) styrene, respectively.

Clinical characterization of patients with primary aldosteronism plus subclinical Cushing's syndrome.

BACKGROUND: Primary aldosteronism (PA) plus subclinical Cushing's syndrome (SCS), PASCS, has occasionally been reported. We aimed to clinically characterize patients with PASCS who are poorly profiled. METHODS: A population-based, retrospective, single-center, observational study was conducted in 71 patients (age, 58.2 ± 11.2 years; 24 males and 47 females) who developed PA (n = 45), SCS (n = 12), or PASCS (n = 14). The main outcome measures were the proportion of patients with diabetes mellitus (DM), serum potassium concentration, and maximum tumor diameter (MTD) on the computed tomography (CT) scans. RESULTS: The proportion of DM patients was significantly greater in the PASCS group than in the PA group (50.0% vs. 13.9%, p <  0.05), without a significant difference between the PASCS and SCS groups. Serum potassium concentration was significantly lower in the PASCS group than in the SCS group (3.2 ± 0.8 mEq/L vs. 4.0 ± 0.5 mEq/L; p <  0.01), without a significant difference between the PASCS and PA groups. Among the 3 study groups of patients who had a unilateral adrenal tumor, MTD was significantly greater in the PASCS group than in the PA group (2.7 ± 0.1 cm vs. 1.4 ± 0.1 cm; p <  0.001), without a significant difference between the PASCS and SCS groups. CONCLUSIONS: Any reference criteria were not obtained that surely distinguish patients with PASCS from those with PA or SCS. However, clinicians should suspect the presence of concurrent SCS in patients with PA when detecting a relatively large adrenal tumor on the CT scans.

Weight control before and during pregnancy for patients with gestational diabetes mellitus.

AIMS/INTRODUCTION: The aim of the present study was to examine the associations of pregestational body mass index (BMI) and gestational weight change with birthweight for gestational age in Japanese mothers with gestational diabetes mellitus (GDM). MATERIALS AND METHODS: We retrospectively examined the clinical and laboratory characteristics of 101 mothers with GDM (pregestational BMI 24.7 ± 5.8 kg/m2 ; maternal age at delivery 34.7 ± 5.1 years; gestational age 38.5 ± 1.4 weeks) at a single center from January 2011 to December 2016. RESULTS: Gestational weight changes were 6.22 ± 5.39 kg, and infant birthweights were 2,987.3 ± 393.6 g. Multivariable analysis showed that, in all mothers, pregestational BMI and gestational weight change were positively associated with infant birthweight (P < 0.001 and P = 0.007, respectively). Pregestational BMI, but not gestational weight change, was positively associated with infant birthweight (P = 0.007) in 31 mothers with GDM who had pregestational BMI ≥25 kg/m2 ; in 68 mothers with GDM who had pregestational BMI 18.5-24.9 kg/m2 , only gestational weight gain was positively associated with infant birthweight (P = 0.039). Two mothers had pregestational BMI <18.5 kg/m2 . No statistically significant interactions of pregestational BMI with gestational weight change were found (P = 0.158). CONCLUSIONS: In mothers with GDM, pregestational BMI ≥25 kg/m2 and excessive gestational weight gain were significantly associated with increased infant birthweight. A prospective multicenter clinical study enrolling a larger number of mothers with GDM will be required to verify the effects of adequately controlling pregestational and gestational weights on infant birthweight for gestational age.

The annual rate of coronary artery calcification with combination therapy with a PCSK9 inhibitor and a statin is lower than that with statin monotherapy.

Statins and/or PCSK9 inhibitors cause the regression of coronary atheroma and reduce clinical events. However, it currently remains unclear whether these drugs modulate coronary atheroma calcification in vivo. Coronary artery calcium (CAC) scores (Agatston Units, AUs) were estimated in 120 patients receiving coronary computed tomographic angiography (CCTA) (63% males; median age 56 years). The CAC scores were compared among the three groups: (1) neither statin nor PCSK9 inhibitor therapy, (2) statin monotherapy, and (3) statin and PCSK9 inhibitor combination therapy in an unpaired cross-sectional study. Additionally, CCTA was performed twice at an interval in 15 patients undergoing statin monotherapy to compare the previous (baseline) and subsequent (follow-up) CAC scores in a paired longitudinal study. In addition, a PCSK9 inhibitor was administered to 16 patients undergoing statin therapy. Before and after that, CCTA was performed twice to compare the previous and subsequent CAC scores in a paired longitudinal study. The unpaired cross-sectional study and paired longitudinal study consist of completely different patients. Among 120 patients, 40 (33%) had a CAC score >100 AUs. The median CAC score increased in the following order: statin group, statin and PCSK9 group, and no-statin-no-PCSK9 group. Annual CAC score progression was 29.7% by statin monotherapy and 14.3% following the addition of the PCSK9 inhibitor to statin therapy. The annual rate of CAC with the combination therapy with a PCSK9 inhibitor and a statin is lower than that with statin monotherapy. CAC may be prevented with PCSK9 Inhibitor.