PURPOSE: Neutrophils found around an infarcted area in the brain was once considered as only the physiologic response following the brain injury, but recent studies have shown that inflammatory responses by neutrophils play an important role in the reperfusion injury. The presence of polymorphonuclear leukocytes(PML) is proven by biochemical assay of myeloperoxidase(MPO) secreted in the cytoplasmic granules. We observed the process of PML infiltration on hypoxic-ischemic brain injury of immature rats by the assay of MPO activity and changes of the MPO activity after the administration of fucoidin, inhibitor of P- and L-selectin. METHODS: We used a well characterized model of the brains of 7 day-old-rats, which had unilateral hypoxic and ischemic injuries(HI). Those injuries were induced by unilateral carotid artery ligation followed by timed exposure to hypoxic inspiratory gas mixture(8% O2). MPO activity was measured in the brain tissue homogenates of HI rats(n=18) at 0, 2, 8, 24 and 48 hrs and in rats that received fucoidin immediately before and again after hypoxia(50 mg/kg, n=6) at 8 and 24 hrs. Controls(n=2) were rats with neither hypoxia nor ischemia. The brain samples were homogenized in 20 mM potassium phosphate buffer(pH 7.4) for 50 secs. The homogenate was centrifuged at 14,000 g at 4degrees C for 15 mins and the supernatant was discarded. The tissue was pulverized, weighed, and suspended in 1 mL of 50 mM potassium phosphate buffer solution(pH 6.0) containing 0.5% cetylditrimethylammonium bromide(wt/vol). The tissue was sonicated and centrifuged at 10,000 g for 15 mins. 200 micro L of the supernatant was mixed with 1 mL of 50 mM potassium phosphate buffer solution(pH 6.0) containing 10 micro L of 1.325 mM o-dianisidine hydrochloride and 170 micro L of 3% hydrogen peroxide(vol/vol). Changes in absorbance at 460 nm were measured for 5 mins by using microplate reader. One unit of MPO activity was defined as that degrading 1 micro mol peroxide/min at 25degrees C, and the result was expressed as units of MPO/100 mg tissue. RESULTS: In HI rats, MPO activity increased at 2 hrs after HI and peaked at 24 hrs in the right hemisphere. In rats with fucoidin treatment immediately before and again after hypoxia, the MPO activity significantly decreased in both hemispheres compared with HI rats(P<0.05). MPO activity in the tissue of control rats was insignificant. CONCLUSION: The dynamic changes of the MPO activity suggest the important role of PMN on hypoxic-ischemic brain injuries in immature rats. MPO activity could be used as an index of the severity of injuries of hypoxic-ischemic brains.
Animals ; Anoxia ; Brain Injuries* ; Brain Ischemia ; Brain* ; Carotid Arteries ; Cerebral Infarction ; Cytoplasmic Granules ; Dianisidine ; Humans ; Hydrogen ; Infant, Newborn ; Ischemia ; L-Selectin ; Ligation ; Neutrophils ; Peroxidase* ; Potassium ; Rats* ; Reperfusion Injury

The spontaneous rupture of splenic artery aneurysm during pregnancy is a rare but catastrophic event. Two thirds of all ruptures happen during the third trimester. Clinical presentation is often non-specific, with good hemodynamic compensation, followed by a rapid deterioration. Active management and operation are the most important procedures for diagnosis and therapy of the bleeding. Abdominal delivery will help to establish diagnosis and should be performed immediately. We report a case of a patient at 38 weeks of gestation suffering epigastric pain and fetal distress. At emergency cesarean delivery, an aneurysmal rupture of the splenic artery was found to be the reason for the hemoperitoneum. Spleen, aneurysm and the tail of the pancreas were removed. In spite of fatal hemorrhage, the patient survived but her fetus was dead. With a review of the literature on this topic, diagnostic aspects and treatment options are discussed.
Aneurysm* ; Cesarean Section ; Compensation and Redress ; Diagnosis ; Emergencies ; Female ; Fetal Distress ; Fetus ; Hemodynamics ; Hemoperitoneum ; Hemorrhage ; Humans ; Pancreas ; Pregnancy ; Pregnancy Trimester, Third* ; Rupture ; Rupture, Spontaneous* ; Spleen ; Splenic Artery*

Objective: Management of heavily pre-treated platinum-resistant ovarian cancer remains a therapeutic challenge. Outcomes are poor with non-platinum, single-agent chemotherapy (CT); however, molecularly targeted anticancer therapies provide new options. Methods: This open-label, investigator-initiated, phase 2 umbrella trial (NCT03699449) enrolled patients with platinum-resistant ovarian cancer (at least 2 prior lines of CT and Eastern Cooperative Oncology Group 0/1) to receive combination therapy based on homologous recombination deficiency (HRD) and programmed death ligand 1 (PD-L1) status determined by archival tumour sample assessment. HRD-positive patients were randomised to either olaparib 200mg bid tablet + cediranib 30mg qd (arm 1) or olaparib 300mg bid tablet + durvalumab 1,500mg q4w (arm 2). HRD-negative patients were allocated to either durvalumab 1,500 mg q4w + pegylated liposomal doxorubicin (PLD) or topotecan or weekly paclitaxel (6 cycles; arm 3, those with PD-L1 expression) or durvalumab 1,500 mg q4w + tremelimumab 75mg q4w (4 doses) + PLD or topotecan or weekly paclitaxel (4 cycles; arm 4, those without PD-L1 expression). Arm 5 (durvalumab 1,500 mg q4w + tremelimumab 300mg [1 dose] + weekly paclitaxel [60 mg/m2 D1,8,15 q4w for 4 cycles] was initiated after arm 4 completed. The primary endpoint was objective response rate (ORR; Response Evaluation Criteria in Solid Tumours 1.1). Results: Between Dec 2018 and Oct 2020, 70 patients (median 57 years; median 3 prior treatment lines [range 2–10]) were treated (n=16, 14, 5, 18, and 17, respectively). Overall ORR was 37.1% (26/70, 95% confidence interval=25.9, 49.5); 2 achieved complete response. ORR was 50%, 42.9%, 20%, 33.3%, and 29.4%, respectively. Grade 3/4 treatment-related adverse events (TRAEs) were reported in 37.5%, 35.7%, 20%, 66.7%, and 35.3% of patients, respectively. No TRAEs leading to treatment discontinuation and no grade 5 TRAEs were observed. Conclusion This study, the first biomarker-driven umbrella trial in platinum-resistant recurrent ovarian cancer, suggests clinical utility with biomarker-driven targeted therapy. All treatment combinations were manageable, and without unexpected toxicities.

Mitochondrial myopathies are diseases caused by defects in metabolic pathway of mitochondria. Mitochondrial myopathy is known as one of the causes of recurrent myoglobinuria, while clinically, rarely causes acute renal failure requiring medical treatments. We report a case of rhabdomyolysis and acute renal failure associated with mitochondrial myopathy. A 58-year-old male was presented with dyspnea and hypotensive shock. The patient had a history of recurrent dark colored urine and cramping leg pain after prolonged fasting. Laboratory findings showed hyperkalemia, azotemia, metabolic acidosis, and elevated AST, ALT, and creatinine kinase. He had no history of trauma or medication. Muscle biopsy showed "ragged red fibers" in modified Gomori staining. On electron microscope, increased number of mitochondria and abnormal mitochondria were seen. He received hemodialysis and his renal function recovered after 1 month.
Acidosis ; Acute Kidney Injury* ; Azotemia ; Biopsy ; Creatinine ; Dyspnea ; Fasting ; Humans ; Hyperkalemia ; Leg ; Male ; Metabolic Networks and Pathways ; Middle Aged ; Mitochondria ; Mitochondrial Myopathies* ; Muscle Cramp ; Myoglobinuria ; Phosphotransferases ; Renal Dialysis ; Rhabdomyolysis* ; Shock

BACKGROUNDS/AIMS: The prognosis of cirrhotic patients with hepatocellular carcinoma (HCC) depends on both residual liver function and tumor characteristics. The aims of this study was to construct a new prognostic index for HCC patients: the modified CLIP score, and to compare its discriminatory ability and predictive power with those of the CLIP score that is currently the most commonly used integrated staging score in patients of HCC. METHODS: A retrospective analysis of 237 cases of HCC diagnosed at Dong-A university hospital was performed. Prognostic analysis was performed for single variables by estimating survival distributions with the Kaplan-Meier's method, and statistically compared by the log-rank test. RESULTS: Patients had a mean age of 57.5 years and were predominantly males (79.7%). The overall median survival period was 25.7 months. It was correlated to ascites, portal vein thrombosis, AFP, tumor size, and Child-Pugh classification. The median survival period was 41.0, 25.2, 13.8, 13.4, and 6.5 months for CLIP scores 0, 1, 2, 3, and 4 to 6, respectively (P<0.001), and 42.1, 34.0, 25.7, 14.0, and 6.8 months for modified CLIP scores 0, 1, 2, 3, and 4 to 6, respectively (P<0.001). The Kaplan-Meier's curve showed that the modified CLIP score had additional explanatory power above that of the CLIP score. CONCLUSIONS: The modified CLIP score, compared with the CLIP score, particularly in the score 2- to 3- patient groups of HCC, had greater discriminant ability and survival predictive power, but was not able to discriminate 4- to 6- patient group.
alpha-Fetoproteins/analysis ; Venous Thrombosis/complications ; Survival Analysis ; Prognosis ; Neoplasm Staging ; Middle Aged ; Male ; Liver Neoplasms/complications/mortality/*pathology ; Liver Cirrhosis/complications ; Humans ; Female ; Carcinoma, Hepatocellular/complications/mortality/*pathology ; Aged, 80 and over ; Aged ; Adult