Leadless Pacemaker Implantation in Severe Kyphosis: Challenging Implantation for Tortuous IVC and Narrow RA.

Leadless pacemaker implantation is recognized as safe and effective for treating bradycardia. However, there are limited descriptions of its use in patients with complex anatomical considerations. Here, we present a case detailing the successful implantation of a leadless pacemaker with a tortuous inferior vena cava and a narrow right atrium.

Long-term outcome and cardiac function after anatomic repair of congenitally corrected transposition.

OBJECTIVES: There is limited information on long-term outcomes and trajectories of ventricular and valvular functions in patients with congenitally corrected transposition of the great arteries after anatomic repair according to the operative strategy with a median follow-up period of more than 10 years. METHODS: Twenty-nine patients who underwent anatomic repair in Okayama University Hospital between January 1994 and December 2020 were reviewed. Outcomes were compared between patients who underwent a double switch operation (DS group) and patients with an atrial switch with a Rastelli operation (Rastelli-Senning/Mustard group). RESULTS: Fifteen (52%) were in the DS group and 14 (48%) were in the Rastelli-Senning/Mustard group. The median follow-up period after anatomic repair was 12.7 (interquartile range 4.2-18.8) years. There were 3 (10%) early deaths and 3 (10%) late deaths. Survival rates for the entire cohort at 10 and 20 years were 86% and 71%, respectively, and were not different between the 2 groups. Using competing risk analysis, risks of heart failure, cardiac rhythm device implantation and atrial arrhythmia showed no significant differences between the 2 groups, whereas risk of reoperation was higher in the Rastelli-Senning/Mustard group than that in the DS group. Four patients after a DS operation and 1 patient after a Rastelli technique developed more than moderate aortic regurgitation. CONCLUSIONS: During a median follow-up period of more than 10 years, mortality rate and ventricular and valvular functions after anatomic repair were acceptable, though the incidences of late complications were relatively high, especially in the Rastelli-Senning/Mustard group.

A sutureless overlapped anastomosis technique using linear staplers with reinforced bioabsorbable material in robotic right colectomy with intracorporeal anastomosis.

AIM: Creation of an overlapped anastomosis using handsewn sutures for common enterotomy is very popular in robotic right colectomy (RRC) with intracorpareal anastomosis (IA). The aim of this study is to present a simple method for constructing a sutureless overlapped anastomosis using a 60 mm linear stapler with a reinforced bioabsorbable material in RRC with IA. METHOD: The distal ileum and proximal colon were put in overlapping positions. Enterotomies were created 2 cm proximal to the ileal stump and 8 cm distal to the colonic stump on the antimesenteric side. Subsequently, a 60 mm linear stapler with a reinforced bioabsorbable material was inserted into each lumen and fired. Finally, the bowel was elevated while holding the bioabsorbable material, and the common enterotomy was grasped with the robotic instrument in the middle and closed using a linear stapler with a reinforced bioabsorbable material. RESULTS: This technique was applied to 10 patients with tumours of the caecum, ascending colon, or transverse colon. The median operating time, anastomosis construction time, blood loss, and postoperative stay were 281 min (range 228-459 min), 12 min (range 11-17 min), 10 mL (range 0-110 mL), and 10 days (range 8-15 days), respectively. No adverse intraoperative events were observed. Postoperatively, one patient developed chylous ascites, but there were no other complications. CONCLUSION: The simple technique for constructing a sutureless overlapped anastomosis using a 60 mm linear stapler with a reinforced bioabsorbable material in robotic right colectomy with intracorporeal anastomosis appears to be safe and feasible.

Proof-of-concept study of the caninized anti-canine programmed death 1 antibody in dogs with advanced non-oral malignant melanoma solid tumors.

BACKGROUND: The anti-programmed death 1 (PD-1) antibody has led to durable clinical responses in a wide variety of human tumors. We have previously developed the caninized anti-canine PD-1 antibody (ca-4F12-E6) and evaluated its therapeutic properties in dogs with advance-staged oral malignant melanoma (OMM), however, their therapeutic effects on other types of canine tumors remain unclear. OBJECTIVE: The present clinical study was carried out to evaluate the safety profile and clinical efficacy of ca-4F12-E6 in dogs with advanced solid tumors except for OMM. METHODS: Thirty-eight dogs with non-OMM solid tumors were enrolled prospectively and treated with ca-4F12-E6 at 3 mg/kg every 2 weeks of each 10-week treatment cycle. Adverse events (AEs) and treatment efficacy were graded based on the criteria established by the Veterinary Cooperative Oncology Group. RESULTS: One dog was withdrawn, and thirty-seven dogs were evaluated for the safety and efficacy of ca-4F12-E6. Treatment-related AEs of any grade occurred in 13 out of 37 cases (35.1%). Two dogs with sterile nodular panniculitis and one with myasthenia gravis and hypothyroidism were suspected of immune-related AEs. In 30 out of 37 dogs that had target tumor lesions, the overall response and clinical benefit rates were 6.9% and 27.6%, respectively. The median progression-free survival and overall survival time were 70 days and 215 days, respectively. CONCLUSIONS: The present study demonstrated that ca-4F12-E6 was well-tolerated in non-OMM dogs, with a small number of cases showing objective responses. This provides evidence supporting large-scale clinical trials of anti-PD-1 antibody therapy in dogs.

Blockade of isoprenoids biosynthesis by simvastatin induces autophagy-mediated cell death via downstream c-Jun N-terminal kinase activation and cell cycle dysregulation in canine T-cell lymphoma cells.

Statins are inhibitors of the mevalonic acid pathway that mediates cellular metabolism by producing cholesterol and isoprenoids and are widely used in treating hypercholesterolaemia in humans. Lipophilic statins, including simvastatin, induce death in various tumour cells. However, the cytotoxic mechanisms of statins in tumour cells remain largely unexplored. This study aimed to elucidate the cytotoxic mechanisms of simvastatin in canine lymphoma cells. Simvastatin induced cell death via c-Jun N-terminal kinase (JNK) activation and autophagy in canine T-cell lymphoma cell lines Ema and UL-1, but not in B-cell lines. Cell death was mediated by induction of caspase-dependent apoptosis in UL-1 cells, but not in Ema cells. Blockade of autophagy by lysosomal inhibitors attenuated simvastatin-induced JNK activation and cell death. Isoprenoids, including farnesyl pyrophosphate and geranylgeranyl pyrophosphate, attenuated simvastatin-induced autophagy, JNK activation, and cell death. In UL-1 cells, simvastatin treatment resulted in the cell cycle arrest at the G2/M phase, which was altered to G0/1 phase cell cycle arrest by treatment with lysosomal inhibitors. These findings demonstrate that depletion of isoprenoids by simvastatin induces autophagy-mediated cell death via downstream JNK activation and cell cycle dysregulation in canine T-cell lymphoma cells.

Plasma cell-free DNA in canine lymphoma patients as a novel material for genotyping.

Canine lymphoma is a disease with high morbidity and poor long-term prognosis, despite a high response rate to chemotherapy. In this study, we focused on liquid biopsy, in which small amounts of substances from body fluids were analysed, to determine whether cell-free DNA (cfDNA) in the plasma can be used as a biomarker for lymphoma in dogs. We found that 23 patients with lymphoma had significantly higher cfDNA concentrations than the 12 healthy dogs (median 2360 ng/mL versus 299 ng/mL, p < .0001). Polymerase chain reaction for antigen receptor rearrangement (PARR) was also employed using cfDNA from the lymphoma group to investigate whether cfDNA could be used for the detection of genetic clonality of lymphomas, as well as the genomic DNA (gDNA) extracted from an original lesion in each case. The correlation of the PARR results between cfDNA and gDNA was observed in 100% of B-cell lymphomas (10/10), 77.8% of T-cell lymphomas (7/9), and 100% of other types of lymphomas (4/4), respectively. These results indicate that plasma cfDNA levels are increasing in canine lymphoma patients, that cfDNA concentration can be a novel diagnostic tool, and that it can be used as a diagnostic tool for PARR.

Factors associated with death, hospitalization, resignation, and sick leave from work among patients with schizophrenia in Japan: a nested case-control study using a large claims database.

BACKGROUND: Premature mortality, frequent relapse that easily leads to hospitalization, and discontinuous employment are key challenges for the treatment of schizophrenia. We evaluated risk factors for important clinical outcomes (death, hospitalization, resignation, and sick leave from work) in patients with schizophrenia in Japan. METHODS: A nested case-control study was conducted for patients with schizophrenia identified in a Japanese claims database. For each outcome, the case was matched with up to four controls of the same age, sex, index year, and enrollment status (employee or dependent family). Potential risk factors were defined by prescriptions or diagnoses within 3 months prior to or in the month of the event. The association among potential risk factors and each outcome was evaluated using multivariable conditional logistic regression analysis with stepwise variable selection. RESULTS: The number of cases and eligible patients for each outcome were 144 and 38,451 (death), 1,520 and 35,225 (hospitalization), 811 and 18,770 (resignation), and 4,590 and 18,770 (sick leave), respectively. Depression was a risk factor for death (odds ratio [OR]: 1.92; 95% confidence interval [CI]: 1.12, 3.29), hospitalization (OR: 1.22; 95% CI: 1.05, 1.42), and sick leave from work (OR: 1.46; 95% CI: 1.36, 1.57). Other risk factors for death were hospitalization history, Charlson Comorbidity Index (CCI) score, and prescription for laxatives. Prescriptions for hypnotics, laxatives, and anticholinergics were risk factors for hospitalization. Prescriptions for hypnotics and anticholinergics were risk factors for resignation. CCI score, prescription for hypnotics, laxatives, and antidiabetics were risk factors for sick leave from work. CONCLUSIONS: Our findings suggest that depression and some physical symptoms, such as constipation and extrapyramidal symptoms, are risk factors for important clinical outcomes in patients with schizophrenia. Attention should be paid to both depression and physical symptoms for the treatment of schizophrenia.

Unique Extraction of a Fractured Pacemaker Lead Adhered to the Spermatic Vein.

Transvenous lead extraction has been increasingly recognized as a safe and effective method of lead extraction, but there are only few references for extracting leads migrating outside the heart. We present a successful extraction of a fractured pacemaker lead from the spermatic vein using several approaches and multiple tools.

Comparison of the subtotal and narrow gastric conduit for cervical esophagogastrostomy after esophagectomy in esophageal cancer patients: a propensity score-matched analysis.

BACKGROUND: Several reports have compared narrow gastric conduit (NGC) with subtotal gastric conduit (SGC) for cervical esophagogastrostomy after esophagectomy; however, whether which one is more beneficial in terms of postoperative complications remains unclear. To determine the optimal gastric conduit type, we retrospectively investigated and compared the postoperative complications between NGC and SGC used in cervical circular-tapered esophagogastrostomy after esophagectomy through a propensity score-matched analysis. METHODS: Between 2008 and 2022, 577 consecutive esophageal cancer patients who underwent esophagectomy and cervical circular-stapled esophagogastrostomy were enrolled in this study. RESULTS: Of the 577 patients, 77 were included each in the SGC and NGC groups, after propensity score matching. Clinical characteristics did not differ between the two groups. The anastomotic leakage rate was significantly lower in the SGC group than in the NGC group (5% vs. 22%, p < 0.01). The anastomotic stenosis rate was significantly higher in the SGC group (16% vs. 5%, p = 0.03). Multivariate logistic analysis showed that NGC, subcutaneous route, and age were significant independent factors associated with anastomotic leakage (odds ratios, 8.58, 6.49, and 5.21; p < 0.01, < 0.01 and 0.03, respectively) and that SGC was a significant independent factor associated with anastomotic stricture (odds ratios, 4.91; p = 0.04). CONCLUSIONS: In cervical circular-stapled esophagogastrostomy after esophagectomy, SGC was superior to NGC in terms of reducing the risk of anastomotic leakage, although the risk of anastomotic stricture needs to be resolved.

Detection of hepatocellular carcinoma during Fontan-associated liver disease follow-up: a report of three cases.

We herein demonstrate three patients diagnosed with early hepatocellular carcinoma (HCC) during follow-up for Fontan-associated liver disease (FALD). Case 1: Twenty-one years after undergoing the Fontan procedure, a 26-year-old female was diagnosed with FALD. At the initial consultation, her serum alpha-fetoprotein (AFP) levels were markedly elevated, and dynamic enhanced computed tomography (CT) revealed HCC measuring 40 mm in diameter. She underwent partial hepatectomy. Ten months later, she underwent conventional transcatheter arterial chemoembolization (cTACE) for recurrent HCC near the resected hepatic stump as a curative treatment. Case 2: Twenty-one years after undergoing the Fontan procedure, a 25-year-old male was diagnosed with FALD and underwent HCC surveillance every 6 months. Thirteen months after the initial consultation, dynamic enhanced CT revealed HCC measuring 10 mm in diameter. He received cTACE as a curative treatment. Case 3. Twenty-eight years after undergoing the Fontan procedure, a 37-year-old male was diagnosed with FALD and underwent HCC surveillance every 3 months. Fourteen months later, abdominal ultrasonography (US) revealed HCC measuring 13 mm in diameter. He received radiofrequency ablation. These cases showed that HCC surveillance using abdominal US and AFP measurements in patients with FALD enables the detection of HCC and increases the chance of a cure.

Evaluation of Quality of Life and Prognosis of Gastric Cancer Patients After Laparoscopic Subtotal Gastrectomy.

BACKGROUND/AIM: The clinical significance of laparoscopic subtotal gastrectomy (LsTG) with a small remnant stomach remains unclear in patients with gastric cancer, including at an advanced stage. The present study assessed postoperative quality of life (QOL) and survival after LsTG compared with laparoscopic total gastrectomy (LTG). PATIENTS AND METHODS: We retrospectively analyzed consecutive patients with gastric cancer who underwent LsTG (n=26) or LTG (n=26). Surgical outcome, postoperative nutritional status, QOL, and prognosis were compared between the LsTG and LTG groups. The Postgastrectomy Syndrome Assessment Scale was used to evaluate postoperative QOL. RESULTS: Operating time was significantly shorter (p<0.01) and postoperative morbidity was significantly lower (p=0.04) in the LsTG than in the LTG group. The reduction in body weight after surgery was significantly greater in the LTG than in the LsTG group (p<0.01). The Postgastrectomy Syndrome Assessment Scale revealed that, compared with LTG, LsTG significantly improved postoperative QOL (p<0.05). There was no significant difference in relapse-free survival and cancer-specific survival between the two groups. Three patients in the LTG group died of pneumonia and overall survival was significantly longer in the LsTG group (p=0.01). CONCLUSION: This study demonstrated the efficacy of LsTG with a small remnant stomach to prevent a decline in postoperative QOL and non-cancer-related death.

MUC5AC and MUC5B expression in canine gallbladder mucocele epithelial cells.

Gallbladder mucocele (GBM) is one of the most common gallbladder diseases in dogs. Its pathogenesis has not yet been clarified, but excessive accumulation of a secretory gel-forming mucin, MUC5AC in the gallbladder has been reported. This study aimed to ascertain if MUC5AC overproduction resulted in mucus accumulation in the gallbladder during GBM development. Eleven dogs undergoing cholecystectomy who were pathologically diagnosed with GBM were included, and the expression level of mucins, particularly MUC5AC and MUC5B, in their gallbladder epithelial cells was compared with those in normal gallbladder epithelial cells. On reverse transcription-quantitative polymerase chain reaction screening, there was a significant difference (P<0.05) in the mRNA expression level of MUC1, but not of other mucins including MUC5AC and MUC5B, between mucocele and normal gallbladder epithelial cells. Protein expression levels were also evaluated for MUC5AC and MUC5B using immunohistochemistry. There was little immunoreactivity for MUC5AC, whereas MUC5B showed definitive staining in gallbladder epithelial cells. There was no difference in MUC5AC and MUC5B protein expression levels between mucocele and normal gallbladder epithelial cells. These data suggest that excessive production of mucin, especially MUC5AC and MUC5B, does not occur in canine GBM, and that abnormal mucus excretion, rather than excessive mucus production, may be the cause of GBM development.

Novel and recurrent COMP gene variants in five Japanese patients with pseudoachondroplasia: skeletal changes from the neonatal to infantile periods.

Pseudoachondroplasia (PSACH) is an autosomal dominant skeletal dysplasia caused by pathogenic variants of cartilage oligomeric matrix protein (COMP). Clinical symptoms of PSACH are characterized by growth disturbances after the first year of life. These disturbances lead to severe short stature with short limbs, brachydactyly, scoliosis, joint laxity, joint pain since childhood, and a normal face. Epimetaphyseal dysplasia, shortened long bones, and short metacarpals and phalanges are common findings on radiological examination. Additionally, anterior tonguing of the vertebral bodies in the lateral view is an important finding in childhood because it is specific to PSACH and normalizes with age. Here, we report five Japanese patients with PSACH, with one recurrent (p.Cys351Tyr) and four novel heterozygous pathogenic COMP variants (p.Asp437Tyr, p.Asp446Gly, p.Asp507Tyr, and p.Asp518Val). These five pathogenic variants were located in the calcium-binding type 3 (T3) repeats. In four of the novel variants, the affected amino acid was aspartic acid, which is abundant in each of the eight T3 repeats. We describe the radiological findings of these five patients. We also retrospectively analyzed the sequential changes in the vertebral body and epimetaphysis of the long bones from the neonatal to infantile periods in a patient with PSACH and congenital heart disease.

Effect of tolvaptan on hyponatremia in a dog with syndrome of inappropriate secretion of antidiuretic hormone.

A 1-year-old spayed female Miniature Schnauzer had chronic hyponatremia, accompanied by polyuria and polydipsia. Blood tests and urinalysis revealed severe hyponatremia, low plasma osmolality with euvolemia, and increased sodium excretion in urine. Hypothyroidism and hypoadrenocorticism were ruled out as causes. These findings led to the diagnosis of syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Magnetic resonance imaging (MRI) showed dilation of the lateral ventricles, indicating severe hydrocephalus. Tolvaptan, a vasopressin V2 receptor antagonist commonly used in human SIADH, was administered along with water restriction. This treatment resulted in a consistent increase in plasma sodium levels without any adverse effects. This case report represents the first documented evidence of the therapeutic efficacy of tolvaptan in treating SIADH in a dog.

Epilepsy in Children With Congenital Heart Disease: Risk Factors and Characteristic Presentations.

BACKGROUND: Children with a congenital heart disease (CHD) are at a higher risk of developing epilepsy than the general population, but detailed characteristics of CHD-associated epilepsy have not been clarified. The purposes of this study were to determine the risk factors for developing epilepsy associated with CHD and to elucidate the characteristics of such epilepsy. METHODS: We performed a retrospective cohort study based on medical records of pediatric patients with CHD who were born between January 2006 and December 2016, underwent cardiac surgery at Okayama University Hospital, and were followed up until at least age three years. Multivariate logistic regression analysis was used to determine factors particularly associated with epilepsy occurrence. In patients who developed epilepsy, clinical data on seizure characteristics were further investigated. RESULTS: We collected data from 1024 patients, and 41 (4.0%) developed epilepsy. The presence of underlying disease (odds ratio [OR]: 2.413; 95% confidence interval [CI]: 1.150 to 4.883) and the Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery score category 2 (OR: 4.373; 95% CI: 1.090 to 29.150) and category 5 (OR: 10.385; 95% CI: 1.717 to 89.016) were significantly related to epilepsy occurrence. Of the 41 patients with epilepsy, 15 (including nine with hypoplastic left heart syndrome) had focal impaired awareness seizures specified as autonomic seizures with vomiting, which tends to escape detection. CONCLUSIONS: We clarified the risk factors for developing epilepsy in children with CHD. We also found that autonomic seizure with vomiting is an important symptom in these children.

Clinical significance of intraperitoneal paclitaxel combined with systemic chemotherapy for gastric cancer with peritoneal metastasis.

BACKGROUND: Despite investigations of intraperitoneal paclitaxel as a personalized treatment for peritoneal metastasis of gastric cancer, few studies have evaluated its prognostic impact on conversion surgery for unresectable gastric cancer with peritoneal metastasis. Our study aimed to close this gap in knowledge. METHODS: We retrospectively enrolled 128 patients who underwent chemotherapy for peritoneal metastasis from gastric cancer and assigned them into intraperitoneal (IP) (n = 36) and non-IP (n = 92) groups, based on the use of intraperitoneal paclitaxel plus systemic chemotherapy. RESULTS: Disease control rates were 94% and 69% in the IP and non-IP groups, respectively, with the former having a significantly higher tumor response rate than the latter (p < 0.01). The median survival times in the IP and non-IP groups were 665 and 359 days, respectively, with the former having significantly better prognosis than the latter (p = 0.02). Fifteen (42%) and sixteen (17%) patients underwent conversion surgery after chemotherapy in the IP and non-IP groups, respectively, with the former having a significantly higher conversion surgery induction rate than the latter (p < 0.01). Although the prognosis of the conversion surgery group was significantly better than that of the non-conversion surgery group (p < 0.01), there was no significant difference in prognosis between patients in the IP and non-IP groups who underwent conversion surgery (p = 0.22). Multivariate analysis identified performance status and conversion surgery as independent prognostic factors (all p < 0.01). CONCLUSION: Our study demonstrated that the IP chemotherapy was one of important factors for conversion surgery induction, while it was not a risk factor for prognosis.

Clinical Significance of Recurrence Risk Score for Conversion Surgery in Patients With Advanced Gastric Cancer.

BACKGROUND/AIM: To develop a recurrence risk score for determining the clinical indication for adjuvant chemotherapy in patients with initially unresectable advanced gastric cancer who underwent conversion surgery after chemotherapy. PATIENTS AND METHODS: A total of 65 patients with stage IV gastric cancer who underwent conversion surgery after chemotherapy were retrospectively enrolled. We established a risk score based on clinicopathological factors related to recurrence after conversion surgery. RESULTS: Out of 65 patients, 40 (62%) had recurrence after conversion surgery. The 5-year overall survival rates in patients with and without recurrence were 14.4% and 87.1%, respectively (p<0.01). Multivariate logistic regression analysis identified the depth of tumor invasion (pT2-4) and histological tumor response (grade 0-1a) as an independent risk factor for disease recurrence (p=0.033 and p=0.048, respectively). A scoring system determined by these two factors was created; total score ranged from 0 to 2 points, and patients were categorized into three groups (scores of 0 vs. 1 vs. 2 points). This scoring system showed that 12 (18%), 15 (23%), and 38 (58%) patients had recurrence risk scores of 0, 1, and 2 points, respectively. There was a close relationship between a high score and the presence of tumor recurrence (p<0.01). Moreover, our model system had a high sensitivity for the prediction of recurrence, compared with the pathological stage. CONCLUSION: Recurrence risk score is a promising tool for assessing the need for adjuvant chemotherapy in patients with initially unresectable advanced gastric cancer after conversion surgery.

Effect of platelet lysate on Schwann-like cell differentiation of equine bone marrow-derived mesenchymal stem cells.

Currently, treatment for peripheral nerve injuries in horses primarily relies upon physical therapy and anti-inflammatory drugs. In humans, various treatments using mesenchymal stem cells (MSCs) are being attempted. Therefore, in this study, Schwann-like cell differentiation cultures of equine MSCs were prepared using fetal bovine serum (FBS) and equine platelet lysate (ePL). ePL increased the platelet count to 1 × 106/µl, the optimal concentration for culture. In both groups, an elongated morphology at both ends, characteristic of Schwann cells, was observed under the microscope. Real-time PCR analysis of the expression levels of neuronal markers showed that the ePL group tended to express higher levels of Nestin, Musashi1, and Pax3 than the FBS group. p75 was expressed at low levels in both groups. Immunostaining results showed localization of Nestin in both groups of differentiated cells, but the positive cell rate was significantly higher in the ePL group than in the FBS group. Overall, the ePL gro showed good results for Schwann-like cell differentiation, which may be useful for future use in the treatment of equine motor neuron disease. This knowledge could be applied translationaly in the treatment of amyotrophic lateral sclerosis in humans.Overall, the ePL group showed good results for Schwann-like cell differentiation, which may be useful for future use in the treatment of equine motor neuron disease and in the treatment of amyotrophic lateral sclerosis in humans.

Longitudinal Measurement of Histidine-Rich Glycoprotein Levels in Bronchopulmonary Dysplasia: A Pilot Study.

Histidine-rich glycoprotein (HRG) has been reported to inhibit signaling leading to the release of high mobility group box 1 protein, a damage-associated molecular pattern. The present study aimed to determine the longitudinal change in HRG levels in extremely preterm infants and assess whether complications such as bronchopulmonary dysplasia (BPD) were associated with differences in HRG levels. In this multicenter, prospective, observational study, we measured serum HRG levels every 2 weeks from birth to 8 weeks of age. Serum HRG was measured using an enzyme-linked immunosorbent assay. We included 19 extremely preterm infants in the study and 74 samples were analyzed. The median gestational age was 26.0 weeks, and the median birth weight was 858 g. Serum HRG levels showed a significant upward trend after birth (p < 0.001); median HRG concentrations at birth and at 2, 4, 6, and 8 weeks of age were 1.07, 1.11, 2.86, 6.05, and 7.49 µg/mL, respectively. Onset of BPD was not associated with differences in serum HRG levels. Further, the serum HRG levels increased significantly after birth in extremely preterm infants.

Decreased sensitivity of cyclin-dependent kinase 4/6 inhibitors, palbociclib and abemaciclib to canine lymphoma cells with high p16 protein expression and low retinoblastoma protein phosphorylation.

Canine lymphoma/leukemia cell lines with p16 protein expressions: high (17-71 and GL-1) and low (CLBL-1, CLC, Nody-1, and UL-1) were treated in vitro with cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, palbociclib or abemaciclib. Cell proliferation decreased as a result, with higher IC50 levels observed in the high p16 (17-71 and GL-1) and one low p16 (UL-1) cell lines compared with the low p16 cells (CLBL-1, CLC, and Nody-1). As expected, palbociclib and abemaciclib treatment reduced pRb phosphorylation in a dose-dependent manner, especially in cells with low p16. These results suggest that CDK4/6 inhibitors have potential as new chemotherapeutic agents for canine lymphoma and high p16 protein expression may be used as a biomarker for resistance to CDK4/6 inhibitor therapy.