Severe Hemorrhage Research Articles

Concurrent diagnosis of severe haemophilia A and acute lymphoblastic leukemia in a child: First report in Greece

Haemophilia A is a congenital bleeding disorder resulting by deficiency of coagulation factor VIII and Acute Lymphoblastic Leukemia (ALL) Is the most common cancer type in children. The concurrence of hemophilia and ALL in pediatric patients is quite rare. We report a case of a 2.5 year old boy, with an uneventful past history, which presented with pallor, petechiae, ecchymoses and lethargy to the emergency department. A full blood count on admission revealed severe leukocytosis, anemia and thrombocytopenia. Diagnosis of ALL was confirmed and the patient was put on chemotherapy. Excessive bleeding from the site of entry of the central venous catheter led to complementary testing, which revealed very low levels of Factor VIII and severe Haemophilia A was also diagnosed. The patient suffered from minor gastrointestinal bleeds and a severe intrabdominal hemorrhage due to an abcess eruption during his treatment for ALL. To date, very few cases of ALL and Haemophilia have been reported in children, and due to this rarity there are no guidelines concerning the adjustments in treatment in this small population of patients.

Analysis of perinatal outcomes in pregnant women with the resolution of placenta previa in the second trimester

Objective: To investigate perinatal outcomes of pregnant women with the resolution of placenta previa in the second trimester. Methods: This study was a retrospective cohort study, which included singleton pregnant women who received prenatal care and delivered at Peking University Third Hospital from January 1st 2019 to December 31st 2020. A total of 403 pregnant women diagnosed with placenta previa by ultrasound at 20-24 weeks of gestation and the placental position returned to normal before delivery were included in the study group, and 403 pregnant women with normal placental position matched 1∶1 were the control group. The primary outcome was postpartum hemorrhage rate, and secondary outcomes included postpartum bleeding volume, severe hemorrhage complications, blood transfusion, drug application, the application of instrument or surgical hemostasis measures, gestational week of delivery, and neonatal outcomes. The perinatal outcomes were analyzed by univariate and multivariate logistic regression methods. Results: (1) Compared with the control group, the incidence of postpartum hemorrhage [10.4% (42/403) vs 17.6% (71/403)], postpartum hemorrhage volume (median: 375 vs 400 ml), the proportion of postpartum hemorrhage≥500 ml [18.6% (75/403) vs 30.5% (123/403)], and the proportion of application of instrument or surgical hemostasis measures [1.7% (7/403) vs 4.5% (18/403)] in the study group were increased, and the differences were statistically significant (all P<0.05). Neonatal outcomes, including birth weight, small for gestational age, hospitalization in neonatal intensive care unit and incidence of neonatal asphyxia, were compared between the two groups, and there were no statistically significant differences (all P>0.05). (2) In pregnant women with vaginal delivery, the postpartum hemorrhage rate [31.7% (66/208) vs 17.5% (39/223)], postpartum hemorrhage volume (median: 390 vs 380 ml), the proportion of instrument or surgical hemostasis measures [3.8% (8/208) vs 0.4% (1/223)] of the study group were higher than those of the control group, and the differences were statistically significant (all P<0.05). There was no significant difference in the rate of postpartum hemorrhage between the study group and the control group who gave birth by cesarean setion (P=0.545), but the proportion of postpartum hemorrhage≥500 ml in the study group and the control group were 29.2% (57/195) and 20.0% (36/180), and the difference was statistically significant (P=0.039). (3) The results of multivariate analysis showed that compared with the control group, the risk of postpartum hemorrhage (aOR=2.042, 95%CI: 1.313-3.175), the application of drugs (aOR=1.684, 95%CI: 1.142-2.484) and the application of instruments or surgical hemostasis measures (aOR=2.696, 95%CI: 1.089-6.675) were significantly increased in the study group (all P<0.05). Among women who delivered vaginally, the risk of postpartum hemorrhage in the study group was 2.021 times greater than that in the control group (95%CI: 1.269-3.220; P=0.003). Conclusion: In women with placental previa in the second trimester of pregnancy, even if the placental position returns to normal before delivery, it is still a high risk factor for postpartum hemorrhage, especially in vaginal delivery.

Essential thrombocythemia complicated by multivessel intracranial dolichoectasia with subarachnoid hemorrhage and recurrent cerebral infarction

BackgroundPatients with essential thrombocythemia (ET) can develop systemic thrombotic and hemorrhagic vascular complications due to increased and dysfunctional platelets.Case presentationWe encountered a 49-year-old Japanese woman with a history of essential ET, cerebral infarction, hypertension, and hyperlipidemia. She had been taking anagrelide (2.5 mg/day) and aspirin (100 mg/day) and had vomited at home. At the time of admission to our hospital, she was in a deep stupor. We thought these symptoms were caused by intracranial hypertension. Head computed tomography showed severe subarachnoid hemorrhage (SAH) at the interhemispheric fissure, hematoma at the corpus callosum, and intraventricular hemorrhages. Digital subtraction angiography demonstrated multiple dilated, stenotic, tortuous intracranial arteries, and a dissecting aneurysm at the right anterior cerebral artery (ACA). The dissecting aneurysm measured 7.7 × 15.5 mm, and a bleb was observed. Our diagnosis was ruptured ACA dissecting aneurysm and diffuse intracranial arterial dolichoectasia (DIADE). We performed stent-assisted coil embolization of the aneurysm. She remained apathetic and manifested unilateral apraxia and alien limb syndrome due to a partial callosal disconnection. Two months thereafter her symptoms gradually improved, her consciousness level and limb function improved, and her modified Rankin scale (mRS) score was 2. However, when we tapered her antiplatelet therapy, she again developed an acute cerebral infarct.ConclusionsThis is the first presentation of a patient with ET complicated by DIADE, both of which can result in ischemic and hemorrhagic vascular complications including SAH. As antithrombotic therapy in patients with DIADE and ET may be associated with higher hemorrhage rates, its effects must be monitored carefully.

Intraventricular baclofen for intractable spasticity and secondary dystonia: a frame-based stereotactic approach and case series

ObjectiveIntraventricular baclofen has been reported as an alternative to intrathecal baclofen for managing refractory spasticity and dystonia in some circumstances. In this report, we described a frame-based stereotactic approach for precisely positioning of the infusion catheter into the third ventricle.Material and methodsHigh resolution contrast-enhanced anatomical MR sequences was acquired prior to surgery for pre-planning. Catheter trajectory was planned to pass from the lateral ventricle to the third ventricle through the Foramen of Monro. The surgical procedure was adapted from the frame-based deep brain stimulation surgery. The Touch-Loc kit (SceneRay, China) was used to temporarily secure the catheter in place during the surgery. From July 2022 to December 2022, three patients suffering from intractable spasticity and/or secondary dystonia received IVB successfully using the described technique.ResultsNo severe adverse events, including death, intracranial hemorrhage, infection, catheter migration or fracture, were documented at the last follow-up (range: 12‒24 months). Transient side effects included mild nausea following the initiation of infusion or the increase in infusion rate. All three patients responded to the IVB.ConclusionsThe described frame-based stereotactic technique for IVB catheter implant is feasible and could be quickly mastered by neurosurgeons in related fields. Larger prospective cohorts with longer follow-up periods are necessary to further evaluate the long-term safety and efficacy of this procedure.

Risk factors of severe postpartum hemorrhage in pregnant women with placenta previa or low-lying placenta: a retrospective cohort study

BackgroundThe severe postpartum hemorrhage (SPPH) leads to dangerous maternal conditions, and its rate is still increasing and the trend in related risk factors is changing. Placenta-related problems remain the high-risk factor for SPPH. The object is to investigate the prevalence and the risk factors of the severe postpartum hemorrhage in pregnant women with placenta previa or low-lying placenta.MethodA retrospective analysis of pregnant women with placenta previa or low-lying placenta after 28 weeks gestation from May 2018 to May 2023 in the Peking Union Medical College Hospital was conducted. The primary outcome was severe postpartum hemorrhage defined as blood loss ≥ 1000 mL within 24 h of childbirth, or with signs or symptoms of low blood volume requiring transfusion of ≥ 4U of red blood cells. Univariate and multivariate logistic regression were used to identify potential risk factors of severe postpartum hemorrhage and receiver operating curve to evaluate the prediction performance.ResultsOf the 14,964 women, 201 met the inclusive criteria. SPPH rate was 1.3% overall and 18.9% in women with placenta previa or low-lying placenta. Weight (aOR = 0.93, 95%CI 0.87–0.99), increta or percreta placenta (aOR = 7.93, 95%CI 2.53–24.77) were the risk factors. The area under the ROC curve was 0.69(95%CI 0.59–0.80) for increta or percreta placenta alone, and 0.72(95%CI 0.62–0.82) for the combination of times of cesarean sections and anterior placenta.ConclusionsPlacenta accreta spectrum was the key independent risk factor of SPPH in women with placenta previa or low-lying placenta. Antenatal risk assessment of SPPH in these population is highly desirable and optimal intervention could be planned.

Severe myelotoxicities related to Th1, Th2, Th17 and Treg CD4+ T cells subpopulations and their cytokine profiles in Mexican children with acute lymphoblastic leukemia during induction of chemotherapy

Abstract Background Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer in the world, and the myelotoxicities due to chemotherapy can lead to severe infections and hemorrhages with high morbidity and mortality. The immune response has implications in the severity of cancer or survival. This immune response is associated with the predominant subpopulations CD4+ T cells and their effector cytokines. However, it is not known if the immune responses are associated with severe myelotoxicities and mortality in children with ALL. Methods To evaluate the contributions of immunological factors on ALL severe myelotoxicities, we identified the Th1, Th2, Th9, Th17, Th22 and Tregs subpopulations of CD4+ T cells according to their chemokine receptor expression patterns in peripheral blood mononuclear cells by flow cytometry. We evaluated also their cytokines levels by Milliplex in serum from 10 children with ALL at diagnosis (day 0), during induction (day 19) and at the end of induction (day 30) between April 2022 and July 2023. Clinical characteristics such age, sex, type and risk of ALL, hemoglobin and platelets levels, absolute neutrophil count, grade of severity and type of myelotoxicities, infections, and hemorrhages were collected. Clinical outcomes as hospitalization care requirements, ICU admission, leukemia remission or relapsed and mortality were followed and documented. Results The age of children was 8.9 years, (SD,5.6; range 2-16), 60% were male sex, all children had pre- B ALL diagnosis, and 80% were intermediate risk-ALL. Th1 cells were predominant at diagnosis (8.1%) and at the end of induction (7.8%), and Th2 cells at day 19 (7.4%), whereas Th17 were significantly decreased at day 30 (2.6%) (p&amp;lt;0.05). Four patients presented bloodstream infection, two by Gram-positive bacteria (Micrococcus, and Streptococcus), one by Klebsiella pneumoniae antimicrobial resistant, and one by Trichosporum asahii. Severe myelotoxicities were presented in 20% of the patients at day19, and in 30% at day 30. Remission was documented in all patients at day 30 and one was identified with early relapse in the follow-up. Three patients (30%) presented poor outcomes, requiring care in ICU and one died (10%) due to fungal infection. Treg cells were significantly predominant in the children who died by fungal infection (p&amp;lt;0.05), with IL-10 level of 84.6 pg/mL but not detectable IL-35 levels. Conclusion Th17 and Treg subpopulations of CD4+ T cells can play an essential role in immune microenvironment during induction related with the severity of the myelotoxicities and infections, and cytokine IL-10 could be used as marker of infection outcome.

Severe maternal morbidity in high income countries

IntroductionWith declining maternal mortality rates in high income countries (HICs), severe maternal morbidity (SMM) is becoming an important quality measure of maternal care. However, there is no international consensus on the definition and types of SMM. This study aims to critically analyze published literature on SMM in HICs. ObjectivesTo compare definitions and criteria used to identify SMM, and to identify the main types and risk factors contributing to SMM in eight HICs. MethodsThree databases were searched, results were filtered, and ten studies were critically appraised. ResultsSix of the articles discussed SMM identification criteria and proposed definition modifications. Longer hospital stay and admission to intensive care unit were suggested as additional criteria. Disease-based criteria was shown to be superior to organ dysfunction criteria. Seven articles detailed common types of SMM as severe haemorrhage, hypertensive disorders, and pre-eclampsia/eclampsia. Six articles described SMM risk factors, of which advanced maternal age and caesarean delivery were most common. DiscussionThis literature review identified disease-based criteria and Canadian study criteria as promising measures of SMM. It also identified several types and risk factors of SMM common between HICs. These findings can help physicians identify women at risk of SMM. The study is however limited to eight HICs and ten studies. Further research should aim to investigate how the measures compare with previous sources of criteria, and to discern the association of weight and race risk factors with SMM.

Signal detection of immune thrombocytopenia associated with immune checkpoint inhibitors

Immune checkpoint inhibitors (ICIs) have become an important treatment modality for various malignancies. Due to excessive inflammatory and immune responses, immune-related adverse events (irAEs), such as rash, pruritis, pneumonitis, hepatitis, hypothyroidism, hyperthyroidism and fatigue, can occur. Acquired immune thrombocytopenia is a rare irAE that can lead to severe low platelet counts and hemorrhage. A retrospective observational analysis was conducted on data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS). We searched for all reports recorded in the FAERS covering the period from 2011 Q1 to 2023 Q4 for target agents. Signal analysis was performed using the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN) and multi-item gamma Poisson shrinker (MGPS) algorithm. Nonparametric tests were used to compare the time to onset of thrombocytopenia-associated fractures between different regimens. There were 404 reports of immune thrombocytopenia in the FAERS database. Immune thrombocytopenia was associated with all ICIs except tremelimumab, and signals were detected by all 4 methods. The median time to the onset of immune thrombocytopenia caused by PD-1, PD-L1 and CTLA-4 inhibitors was 47 days (range: 21-139.2), 21 days (range: 13–131) and 9 days (range: 7–27), respectively. The Weibull shape parameter test revealed that pembrolizumab-, durvalumab-, and ipilimumab-induced thrombocytopenia had a random failure-type profile, and nivolumab- and atezolizumab-induced thrombocytopenia were characterized by an early failure-type profile. There was a significant reporting signal of ICI-induced thrombocytopenia associated with most ICIs. Immune thrombocytopenia has a greater incidence in males, elderly individuals and Asian populations, and PD-1 inhibitors were the most common cause. Clinicians should be aware of the signs of potential serious adverse events.

Acute Corrosive Acid Ingestion: A Case Series of Four Autopsies

Acute corrosive acid ingestion presents significant challenges in clinical and forensic pathology due to its severe and often fatal outcomes. This case series examines four autopsies involving fatal acid ingestion: three cases of hydrochloric acid (HCl) poisoning and one case of sulfuric acid (H₂SO₄) poisoning. Each case provides detailed autopsy findings, focusing on macroscopic and microscopic pathological changes. The first three cases of HCl poisoning revealed extensive tissue damage characterized by coagulative necrosis, particularly affecting the esophagus, stomach, and duodenum. Histological examination showed dense inflammatory infiltrate, submucosal edema, and significant hemorrhage, with patchy necrosis observed in the liver and kidneys. Pulmonary findings included alveolar edema and hemorrhage. The fourth case, involving H₂SO₄ ingestion, demonstrated more severe injuries with transmural necrosis and extensive hemorrhagic infiltration in the esophagus. The stomach exhibited full-thickness necrosis with a pronounced sulfurous odor, indicating severe chemical injury. Histopathological findings included extensive tissue dehydration and charring, with severe alveolar edema and hemorrhage in the lungs and extensive necrosis in the liver and kidneys. Comparative analysis of the histopathological changes highlighted the differences in tissue damage caused by these two acids. HCl primarily induced superficial necrosis with relatively preserved tissue architecture, while H₂SO₄ caused more extensive and deeper tissue damage due to its strong dehydrating and exothermic properties. Recognizing these differences is crucial for forensic pathologists in accurately diagnosing and differentiating cases of acid poisoning, ultimately enhancing diagnostic precision and clinical outcomes. This study underscores the severe and often fatal consequences of acute acid ingestion and aims to enhance the understanding of the pathological changes associated with such poisonings, thereby improving forensic and clinical evaluations.

6705 Sheehan syndrome: a case report

Abstract Disclosure: F.S. Rodrigues: None. C.C. Silva: None. W. Da Silva: None. T.M. Caldas: None. L. Rocha: None. Introduction: Sheehan's Syndrome, or postpartum hypopituitarism, is characterized by hyperplasia and an increase in the number of prolactin-secreting cells, secondary to a major hemorrhagic event occurring during or after childbirth. In this situation, the anterior pituitary gland can increase in size and suffer ischemia due to vascular hypoflow. Consequently, there is low production of one or more of the hormones produced by the gland, which can generate heterogeneous clinical presentations. As a preventive treatment, polytransfusion is recommended in cases of large hemorrhage. OBJECTIVE: To present a case of Sheehan’s Syndrome, which developed after a birth complicated by a major hemorrhagic event, even after receiving polytransfusion. CASE REPORT: A woman, 45 years old, being monitored at the endocrinology outpatient clinic for 2 years. As a history, there was a severe hemorrhage during her cesarean section, which occurred 30 years ago, in which she received a blood transfusion of a total of 1.2 liters of packed red blood cells. 7 years ago, she was diagnosed with hypothyroidism and 2 years ago with hyperprolactinemia. In 2022, she was also diagnosed with adrenal insufficiency. At that time, she underwent a magnetic resonance imaging (MRI) scan of the sellaturcica region, which was found to be partially empty. The patient's recent exams showed TSH: 3.15 μUI/mL (0.4-4.0); Free T4: 0.88 ng/dL (0.93-1.7); Cortisol 8h: 8 μg/dL (5-25); LH: 15 mIU/mL (1.1-14.7); FSH: 43 mIU/mL (2.8-9); Estradiol: 8 ng/dL (12.4-398); Prolactin: 28 ng/mL (1.9-25), basal GH 0’ 0.054/30’ 2.51/60’ 2.48/90’ 3.74 ng/mL (up to 10), ACTH 17 pg/mL (up to 46). Since then, she has been undergoing endocrinological monitoring for hormone replacement therapy to treat the hormonal changes caused by late-diagnosed Sheehan Syndrome. DISCUSSION: Sheehan's Syndrome is a rare disease, characterized by low blood flow and necrosis of the pituitary gland due to postpartum hemorrhage. The diagnosis results from obtaining a good clinical history associated with hormonal levels. This patient presented significant bleeding after cesarean section requiring transfusions. However, despite transfusions, the patient developed hypothyroidism, hyperprolactinemia, and adrenal insufficiency. The MRI confirmed the suspected diagnosis, showing the partially empty sellaturcica. Conclusion: The diagnosis of Sheehan Syndrome is based on very broad clinical manifestations, with MRI of the sellaturcica contributing to confirming the diagnosis. Although the preventive treatment is blood transfusion, the patient developed the disease, highlighting the need for continued monitoring of pregnant women with a history of significant bleeding during childbirth. Therefore, outpatient monitoring of the patient is necessary with a focus on hormonal levels so that clinical complications are avoided. Presentation: 6/2/2024

8144 Hypertension in Sheehan Syndrome: A Diagnostic Challenge

Abstract Disclosure: E. Ahsan: None. F.F. Foo: None. C. Lesniak: None. M. Akula: None. K. Hu: None. R. Ong: None. K. Chalasani: None. J. Cheng: None. S. Holland: None. Introduction: Postpartum pituitary necrosis, commonly known as Sheehan syndrome (SS), is the term used to describe the necrosis of anterior pituitary gland cells that occurs after significant postpartum bleeding, hypovolemia, and shock. This typically occurs after delivery, during which the mother suffers significant blood loss. The pituitary gland fails to produce hormones due to this blood loss. Depending on the degree of tissue damage, SS can have an acute or chronic course, and patients may present with a wide range of clinical symptoms at diagnosis. Acute SS is associated with postpartum pituitary infarction, which can result in hypotension, shock, hypoglycemia, hyponatremia, headache, vision disturbances, unconsciousness, and an inability to lactate. We present a rare case of SS where the patient experienced hypertension instead of classic hypotension due to postpartum preeclampsia. Clinical Case: A 40-year-old female with no significant medical history presented to the hospital for scheduled induction of labor for polyhydramnios and underwent vacuum-assisted vaginal delivery and postpartum hysterectomy due to severe postpartum hemorrhage secondary to DIC. The postpartum course was also complicated by preeclampsia with severe features. Patients developed features like excessive fatigue, hypoglycemia, hyponatremia, hypothyroidism, polyuria, and failure of lactation, which were consistent with panhypopituitarism secondary to Sheehan syndrome. However, the patient was hypertensive to 145/91 before steroids were given. Labs were significant for serum sodium 116 mmol/L (135-145 mmol/L), FSH &amp;lt;0.7 mIU/mL (Follicular Phase: 2.5-10.2, Mid-cycle Peak: 3.1-17.7, Luteal Phase: 1.5-9.1, Postmenopausal: 23.0-116.3), LH &amp;lt;0.2 mIU/m (Follicular Phase: 1.9-12.5, Mid-Cycle Peak: 8.7-76.3, Luteal Phase: 0.5-16.9, Postmenopausal: 10.0-54.7), Prolactin: 2.4 ng/mL (Non-pregnant: 3.0-30.0, Pregnant: 10.0-209.0, Postmenopausal: 2.0-20.0), PM Cortisol on admission: 1.10 ug/dL (3.44-16.76 ug/dL), plasma ACTH 7 pg/mL( 6 - 50 pg/mL), TSH 0.430 uIU/mL (0.550 - 4.780 uIU/mL), FT4 0.59 ng/dL - 1.76 ng/dL). MRI of the brain pituitary showed- A 1.5 cm region of hypoenhancement and an additional 2 mm focus of hypoenhancement in the sella, findings represent evolving pituitary necrosis. The patient received 24 units of blood transfusion and hormone replacement therapy, followed by outpatient endocrinology follow-up. Clinical lessons: Although considerable blood loss causes hypotension in patients with SS, additional postpartum medical issues can sometimes result in atypical presentations. In our patient, postpartum preeclampsia caused hypertension. Identifying the atypical symptoms of SS is just as vital as identifying its typical features to prevent potentially fatal consequences. Presentation: 6/2/2024

6672 Pituicytomas and Spindle Cell Oncocytomas: Rare Posterior Pituitary Tumors

Abstract Disclosure: Y. Park: None. A. Shen: None. M. Christie: None. J. Wentworth: None. C.J. Yates: None. J. King: None. Background: Pituicytomas and spindle cell oncocytomas (SCO) are rare non-functioning benign posterior pituitary tumors that can present as suprasellar or sellar-suprasellar masses.[1] Pituicytomas originate from the pituicytes in the neurohypophysis and infundibulum of the pituitary gland.2 SCO were previously thought to derive from the adenohypophysis,3 however, are now classified as a tumor of the neurohypophysis characterized by immunohistochemical reactivity to thyroid transcription factor 1 (TTF1).4 According to the World Health Organization 2021 classifications, pituicytomas, granular cell tumors and SCO may represent morphologic variations of the same tumor expressing TTF1.5 Due to their rarity, their clinical characteristics are not yet well-defined and can be mistaken as non-functioning pituitary adenomas. Methods: We retrospectively reviewed the clinical data of two patients with pituicytomas and two patients with SCO confirmed on histopathology at our institution, evaluating their clinical characteristics and management outcomes. Results: Two male patients, aged 59 and 79, were diagnosed with pituicytoma, and two male patients, aged 33 and 55 were diagnosed with SCO. Three presented with visual impairment from mass effects and three patients had hypogonadotropic hypogonadism. None had pre-operative arginine vasopressin (AVP) deficiency. All lesions were isointense on T1-weighted, and most were hyperintense on T2-weighted magnetic resonance imaging. Three cases had non-gross total resection due to hypervascularity. Postoperatively, two patients developed AVP deficiency and three developed persistent anterior pituitary insufficiency (Table 1). Pituicytomas had a Ki67 of 1-3%, and SCO had a Topoisomerase labelling index of &amp;lt;1%. In one case of pituicytoma, due to tumor recurrence 2 years after initial surgery, adjuvant radiotherapy was considered. However, the patient developed a severe peri-tumoral subarachnoid hemorrhage and died prior to receiving radiotherapy. In contrast, the progression of the residual SCO occurred at a slower rate. Discussions: Posterior pituitary tumor differentials are broad, including pituicytoma, SCO, granular cell tumor, craniopharyngioma, meningioma and germinoma;6 hence, histopathological diagnosis is crucial. Although benign, pituicytomas and SCO can result in increased morbidity and postoperative complications, such as AVP deficiency and hypopituitarism. Recurrence and progression are common.7, 8 Gross total resection is optimal, but this is difficult due to hypervascularity.9 Our case of peri-tumoral subarachnoid hemorrhage resulting in death emphasizes the hypervascular nature of pituicytomas. Patients with pituicytomas and SCO should be monitored for tumor progression or recurrence and hemorrhagic complications. Adjuvant radiotherapy may be considered for the management of tumor recurrence. Presentation: 6/3/2024

Stroke severity and outcomes in patients with intracerebral hemorrhage on anticoagulants and antiplatelet agents: an analysis from the Japan Stroke Data Bank.

Some patients with intracerebral hemorrhage are on antithrombotic agents at the time of the event and these may worsen outcome, but the relative risk of different oral anticoagulants and antiplatelet agents is uncertain. We determined associations between pre-onset intake of antithrombotic agents and initial stroke severity, and outcomes, in patients with intracerebral hemorrhage. Patients with intracerebral hemorrhage admitted within 24 hours after onset between January 2017 and December 2020 and recruited to the Japan Stroke Data Bank, a hospital-based multicenter prospective registry, were included. Enrolled patients were classified into four groups based on the type of antithrombotic agents being used on admission. The outcomes were the National Institutes of Health Stroke Scale (NIHSS) score on admission and modified Rankin Scale (mRS) of 5-6 at discharge. Of a total 9,810 patients with intracerebral hemorrhage (4,267 females; mean age, 70±15 years), 77.1% were classified into the no-antithrombotic group, 13.2% into the antiplatelet group, 4.0% into the warfarin group, and 5.8% into the direct oral anticoagulant (DOAC) group. Median (interquartile range) NIHSS score on admission was 12 (5-22), 13 (5-26), 15 (5-30), and 13 (6-24), respectively, in the four groups. In multivariable analysis, the pre stroke warfarin use was associated with higher NIHSS score (adjusted incidence rate ratio, 1.09 [95%confidence interval (CI), 1.06-1.13], with the no-antithrombotic group as the reference), but the antiplatelet group (1.00 [95%CI, 0.98-1.02]) and DOAC group (0.98 [95%CI, 0.95-1.01]) was not. The rate of mRS 5-6 at discharge was 30.8%, 41.9%, 48.6%, and 41.5%, respectively, in the four groups. In multivariable analysis, pre stroke warfarin use was associated with mRS 5-6 (adjusted odds ratio: 1.90 [95%CI, 1.28-2.81], with the no-antithrombotic group as the reference), but the antiplatelet group (1.12 [95%CI, 0.91-1.37]) and DOAC group (1.25 [95%CI, 0.88-1.77]) was not. Patients who were taking warfarin prior to intracerebral hemorrhage onset suffered more severe intracerebral hemorrhage as evidenced by higher admission NIHSS and higher discharge mRS. In contrast, no increase in severity was seen with antiplatelet agents.

Association of neonatal outcome with birth weight for gestational age in Chinese very preterm infants: a retrospective cohort study

BackgroundThe neonatal outcomes across different percentiles of birth weight for gestational age are still unclear.MethodsThis retrospective cohort study was conducted within 57 tertiary hospitals participating in the Chinese Neonatal Network (CHNN) from 25 provinces throughout China. Infants with gestational age (GA) 24+0-31+6 weeks who were admitted within 7 days after birth were included. The composite outcome was defined as mortality or any one of neonatal major morbidities, including necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), severe intraventricular hemorrhage (IVH), cystic periventricular leukomalacia (cPVL), severe retinopathy of prematurity (ROP), and sepsis. Multivariable logistic regressions using generalized estimating equation approach were conducted.ResultsA total of 8380 infants were included with a mean GA of 30 (28–31) weeks. Of these, 1373 (16.5%) were born at less than 28 weeks, while 6997 (83.5%) had a GA between 28 and 32 weeks. Our analysis indicated that the risk of composite outcomes was negatively associated with birth weight for gestational age, and compared to the reference group, the multiple-adjusted ORs (95%CI) of composite outcomes were 4.89 (3.51–6.81) and 2.16 (1.77–2.63) for infants with birth weight for gestational less than 10th percentile and 10th -30th percentile, respectively. The ORs (95%CI) of mortality, NEC, BPD, severe ROP, and sepsis in infants with birth weight for gestational age at 10th-30th percentile were 1.94 (1.56–2.41), 1.08 (0.79–1.47), 2.48 (2.03–3.04), 2.35 (1.63–3.39), and 1.39 (1.10–1.77), respectively.ConclusionOur study suggested that the risk of adverse neonatal outcomes increased significantly when the birth weight for gestational age was below the 30th percentile. Regular monitoring and early intervention are crucial for these high-risk infants.

Antenatal maternal serum biomarkers as a predictor for placenta accreta spectrum disorders

IntroductionPlacenta accreta spectrum (PAS) disorder, an abnormal adherence of the placenta to the uterine wall, with variable degrees of invasion, is a major cause of maternal morbidity and mortality associated with severe postpartum hemorrhage. PAS is diagnosed using ultrasonography or with magnetic resonance imaging; in many centers there is a lack of PAS diagnostic expertise in diagnosing. Hence, we investigated the performance of selected maternal plasma protein biomarkers, antithrombin-III (AT-3), plasminogen activator inhibitor-I (PAI-I), soluble vascular endothelial growth factor receptor-II (sVEGFR-2), and soluble Tie-II (sT-2) for prenatal screening in pregnancies at a high risk of PAS. MethodsThis prospective study, conducted in a tertiary hospital from September 2021 to May 2022, included pregnant women with placenta previa suspicious of PAS between 28 and 42 weeks of gestation. Four serum samples were collected from each woman to evaluate serum concentrations and compared between placenta previa (control) and PAS groups. The screening performances of the biomarkers were analyzed, and the best screening model for PAS was created. ResultsTwenty-two women with PAS and 18 with placenta previa alone were included (n = 40). The median concentrations of PAI-I, AT-3, sVEGFR-2, and sT-2 among the PAS group were 21.2, 6154.6, 7.5, and 12.8 ng/mL, respectively. The best screening model for PAS combined all four biomarkers with a history of cesarean delivery (77 % sensitivity, 89 % specificity, and an AUC of 0.87). DiscussionA combination of the four maternal serum biomarkers in women with a history of cesarean delivery presented the most promising model for prenatal screening of PAS. ConclusionA combination of the four maternal serum biomarkers with a history of cesarean delivery presented the most promising model for prenatal screening of PAS.

Neuroendoscopic surgery for brainstem hemorrhage: Technical notes and preliminary clinical results

BackgroundBrainstem hemorrhage accounts for a relatively small proportion of spontaneous intracerebral hemorrhages (∼10 %) but tends to occur earlier in life and has poorer prognosis. Numerous studies support the therapeutic potential of minimally invasive hematoma evacuation for intracerebral hemorrhage; however, there have been few assessments of the benefits for brainstem hemorrhage. MethodsWe evaluated the safety and efficacy of a minimally invasive approach under neuroendoscopic guidance with pneumatic arm fixation for removing the hematoma in severe brainstem hemorrhage patients. 14 patients diagnosed with primary brainstem hemorrhage and treated by neuroendoscopy-assisted evacuation at Suzhou Ninth Hospital affiliated to Soochow University were included in the study. Relevant clinical and prognostic date were collected and analyzed. ResultsHematoma volume ranged from 8 to 13 mL according to preoperative CT, while GCS at admission ranged from 4 to 6. The average operative time was 157 min and average intraoperative blood loss was 86 mL. All patients achieved satisfactory hematoma evacuation (over 90 %) according to immediate postoperative CT. Postoperative intensive care unit stay averaged 9.5 days and respiratory support averaged 7.5 days. 11 patients required tracheotomy due to pulmonary infection and absence of pharyngeal reflexes. 9 patients achieved satisfactory functional recovery (GOS score of 4 and 3), while 5 remained in a vegetative state (GOS score of 2). ConclusionNeuroendoscopy provides excellent direct visualization of brainstem hematomas for safe and reliable evacuation. Patients with a new PPH score of 2 or 3 are more likely to benefit from surgical treatment. Large-scale studies are required to identify patients most likely to benefit from this technique.

Effect of Mild Therapeutic Hypothermia Combined with Stereotactic Aspiration on Patients with Severe Cerebral Hemorrhage.

This study aimed to investigate the effects of mild therapeutic hypothermia combined with stereotactic aspiration of spontaneous intracerebral hematoma on neurological function, inflammatory markers, cerebral hematoma, and cerebral edema in patients with severe cerebral hemorrhage. The clinical data of 86 patients with severe cerebral hemorrhage treated at our hospital between March 2020 and January 2022 were retrospectively analyzed. The patients were grouped according to their treatment plans: the control group consisted of 40 patients who underwent stereotactic aspiration of the spontaneous intracerebral hematoma, whereas the study group consisted of 46 patients who received adjuvant mild therapeutic hypothermia in addition to the aforementioned treatment. Clinical efficacy, neurological function (NIHSS score), daily living ability (BI score), cerebral hematoma, cerebral edema, cerebral hemodynamics (PI, RI, Vm, Vd), inflammatory markers (IL-6, IL-8, TNF-α, hs-CRP), oxidative stress indicators (SOD, MDA, 8-iso-PGF2α), serum-related factors (MMP-9, ICAM-1, ET-1, NO), and prognosis were compared between the groups. The total efficacy rate in the study group (95.65%) was significantly higher than that in the control group (77.50%) (P < 0.05). Post-treatment NIHSS scores, intracranial hematoma volume, perihematoma edema volume, cerebral edema volume, RI, serum IL-6, IL-8, TNF-α, hs-CRP, MDA, and 8-iso-PGF2α levels were significantly lower in both groups, with the study group showing even greater reductions. The BI score and PI, Vm, Vd, SOD, and NO levels were significantly higher in the study group (P < 0.05). At the 6-month follow-up, the prognosis of patients in the intervention group was significantly better than that of patients in the control group (P < 0.05). The combination of mild therapeutic hypothermia with stereotactic aspiration of a spontaneous intracerebral hematoma has demonstrated efficacy in the treatment of severe cerebral hemorrhage. This approach effectively reduces cerebral hematoma and edema, improves daily living ability, alleviates neurological deficits, regulates cerebral hemodynamics, suppresses inflammatory responses and oxidative stress, modulates serum-related factor levels, and enhances patient prognosis.

The impact of volume and neonatal level of care on outcomes of moderate and late preterm infants.

Evaluate the relationship of neonatal unit level of care (LOC) and volume with mortality or morbidity in moderate-late preterm (MLP) (32-36 weeks' gestation) infants. Retrospective cohort study of 650,865 inborn MLP infants in 4976 hospitals-years using 2003-2015 linked administrative data from 4 states. Exposure was combined neonatal LOC and MLP annual volume. The primary outcome was death or morbidity (respiratory distress syndrome, severe intraventricular hemorrhage, necrotizing enterocolitis, sepsis, infection, pneumothorax, extreme length of stay) with components as secondary outcomes. Poisson regression models adjusted for patient characteristics with a random effect for unit were used. In adjusted models, high-volume level 2 units had a lower risk of the primary outcome compared to low-volume level 3 units (aIRR 0.90 [95% CI 0.83-0.98] vs. aIRR 1.13 [95% CI 1.03-1.24], p < 0.001) CONCLUSION: MLP infants had improved outcomes in high-volume level 2 units compared to low-volume level 3 units in adjusted analysis.

Surgical management of severe noncompressible torso and organ hemorrhages

Noncompressible torso hemorrhages (NCTH) are now recognized as the leading cause of preventable death in the context of severe military and civilian injuries. Approximately 20% of all trauma patients still die from uncontrolled bleeding associated with rapidly evolving disorders of blood coagulation function. Summary of recent advances in the field of nonsurgical and surgical management, presentation of current treatment concepts and future research directions. Selective literature review and analysis. The concepts for the early treatment of NCTH have considerably evolved over the last decade. The updated definition of NCTH includes acombination of high-grade anatomic body trunk injury, hemodynamic instability, urgent need for hemorrhage control, and aggressive hemostatic treatment. The treatment concepts consider the following 3 aspects: controlling the source of bleeding (close the tap), maintaining organ perfusion and restoring hemostasis (fill the tank) and increasing the body's resistance to ischemia (upgrade the armor). New tools, well-established damage control concepts and early and aggressive therapeutic intervention for hemostatic failure have significantly improved the outcomes. Future research needs to refine and validate the current concepts for further clinical application.

High expression of CD3+T-lymphocytes in cerebrospinal fluid increases the risk of critical cerebral hemorrhage with systemic inflammatory response syndrome (SIRS) after surgery

ObjectiveTo assess the frequency of lymphocyte subsets and other laboratory indicators in paired cerebrospinal fluid (CSF) and peripheral blood (PB) samples from critically ill patients with intracerebral hemorrhage (ICH) who developed systemic inflammatory response syndrome (SIRS) following surgery. IntroductionNeuroinflammation and systemic inflammatory responses significantly contribute to secondary brain injury following ICH. Post-surgery SIRS is known to worsen clinical outcomes in ICH patients; however, the immune response in the CSF and PB has not been fully characterized. Understanding immunological changes in ICH patients with SIRS could lead to improved clinical management and prognostic outcomes. MethodsThis study involved a retrospective analysis of data from patients with ICH who underwent surgery in the Neurological Intensive Care Unit (NICU) of Baoding No. 1 Hospital, Hebei Province, China, between January and July 2022. Patients were divided into SIRS and non-SIRS groups based on the clinical criteria. Demographic, clinical, and laboratory data, including lymphocyte subsets in CSF and PB, were collected and analyzed. This study compared lymphocyte subsets and other inflammatory markers between the SIRS and non-SIRS groups. ResultsPatients with SIRS demonstrated higher systolic blood pressure (SBP) at admission, worse 90-day prognoses, elevated inflammatory markers, increased levels of complement proteins C3 and C4, and lower levels of immunoglobulin G (IgG) compared to patients without SIRS. Between 3–6 days post-surgery, SIRS patients showed higher percentages of CD3+T cells, CD4+T cells, and CD4+/CD8+ ratios in the CSF than non-SIRS patients. CD3+T cell percentages in the CSF were consistently higher than those in the PB and were independent of PB levels. In contrast, CD3-CD16+CD56+ natural killer (NK) cell percentages were lower in patients with SIRS. No significant differences in PB lymphocyte subsets were found between the two groups. A high CSF CD3+T cell percentage (≥85.68 %) was identified as the strongest predictor of critical ICH with SIRS after surgery, with an appropriate use criterion (AUC) of 0.7742, sensitivity of 77.42 %, specificity of 76.19 %, and 95 % CI of 0.6655–0.8829 (P < 0.0001). ConclusionElevated levels of CD3+T lymphocytes in CSF are strongly associated with an increased risk of severe cerebral hemorrhage and SIRS following surgery. These findings suggest that monitoring CSF immune markers, particularly CD3+T lymphocytes, could serve as valuable predictors for the development of SIRS in critically ill ICH patients and inform post-surgical treatment strategies.