Abdominal compartment syndrome secondary to a large retroperitoneal hematoma caused by ruptured gastroduodenal artery pseudoaneurysms in a patient with severe acute pancreatitis.

Background: Abdominal compartment syndrome (ACS) is a known complication of severe acute pancreatitis. It is typically secondary to visceral edema and aggressive fluid resuscitation, but rarely caused by a retroperitoneal hematoma due to ruptured visceral pseudoaneurysms. Case Presentation: A 49-year-old man presented in shock with a history of heavy alcohol use and was transferred to the intensive care unit with a diagnosis of severe acute pancreatitis. Computed tomography scan on hospital day 2 revealed a large retroperitoneal hematoma due to ruptured gastroduodenal artery pseudoaneurysms. Despite adequate resuscitation, the patient developed ACS, which required decompressive laparotomy on hospital day 10. Open abdominal management was continued until multiorgan failure resolved. He was eventually discharged to a rehabilitation hospital 3 months after presenting. Conclusion: We report a patient with severe acute pancreatitis who underwent decompressive laparotomy for ACS secondary to a large retroperitoneal hematoma due to ruptured gastroduodenal artery pseudoaneurysms.

Heat stroke management during the COVID-19 pandemic: Recommendations from the experts in Japan (2nd edition).

Both coronavirus disease 2019 (COVID-19) and heat stroke have symptoms of fever or hyperthermia and the difficulty in distinguishing them could lead to a strain on emergency medical care. To mitigate the potential confusion that could arise from actions for preventing both COVID-19 spread and heat stroke, particularly in the context of record-breaking summer season temperatures, this work offers new knowledge and evidence that address concerns regarding indoor ventilation and indoor temperatures, mask wearing and heat stroke risk, and the isolation of older adults. Specifically, the current work is the second edition to the previously published guidance for handling heat stroke during the COVID-19 pandemic, prepared by the "Working group on heat stroke medical care during the COVID-19 epidemic," composed of members from four organizations in different medical and related fields. The group was established by the Japanese Association for Acute Medicine Heatstroke and Hypothermia Surveillance Committee. This second edition includes new knowledge, and conventional evidence gleaned from a primary selection of 60 articles from MEDLINE, one article from Cochrane, 13 articles from Ichushi, and a secondary/final selection of 56 articles. This work summarizes the contents that have been clarified in the prevention and treatment of infectious diseases and heat stroke to provide guidance for the prevention, diagnosis, and treatment of heat stroke during the COVID-19 pandemic.

Current status of active cooling, deep body temperature measurement, and face mask wearing in heat stroke and heat exhaustion patients in Japan: a nationwide observational study based on the Heatstroke STUDY 2020 and 2021.

Aim: The study aimed to determine the current status of face mask use, deep body temperature measurement, and active cooling in patients suffering from heat stroke and heat exhaustion in Japan. Methods: This was a prospective, observational, multicenter study using data from the Heatstroke STUDY 2020-2021, a nationwide periodical registry of heat stroke and heat exhaustion patients. Based on the Bouchama heatstroke criteria, we classified the patients into two groups: severe and mild-to-moderate. We compared the outcomes between the two groups and reclassified them into two subgroups according to the severity of the illness, deep body temperature measurements, and face mask use. Cramer's V was used to determine the effect sizes for a comparison between groups. Results: Almost all patients in this study were categorized as having degree III based on the Japanese Association for Acute Medicine heatstroke criteria (JAAM-HS). However, the severe group was significantly worse than the mild-to-moderate group in outcomes like in-hospital death and modified Rankin Scale scores, when discharged. Heat strokes had significantly higher rates of active cooling and lower mortality rates than heat stroke-like illnesses. Patients using face masks often use them during labor, sports, and other exertions, had less severe conditions, and were less likely to be young male individuals. Conclusions: It is suggested that severe cases require a more detailed classification of degree III in the JAAM-HS criteria, and not measuring deep body temperature could have been a factor in the nonperformance of active cooling and worse outcomes.

Rapid elevation of brain-derived neurotrophic factor production in the bilateral trigeminal ganglia by unilateral transection of the mental nerve in mice.

OBJECTIVES: Previous spinal nerve injury studies have reported brain-derived neurotrophic factor (BDNF) mRNA upregulation in either the ipsilateral dorsal root ganglion (DRG) neurons or both the contralateral and ipsilateral DRG neurons from early period after peripheral nerve injury. This BDNF elevation induces hyperalgesia in the injured and/or uninjured sites, but this detailed mechanism remains unknown. This study aimed to investigate the BDNF mRNA expression in bilateral DRG neurons caused by unilateral nerve injury and to explore the possible mechanisms by which nitric oxide (NO) mediates BDNF production in the DRG, resulting in contralateral hyperalgesia. METHODS: Early changes in BDNF mRNA expression in the bilateral trigeminal ganglia, within 1 day after mental nerve transection, were examined. Additionally, the effects on BDNF production of the NO synthase inhibitor N(ω)-nitro-l-arginine methyl ester (L-NAME) were investigated in the bilateral trigeminal ganglia. The relationship between injured neurons and BDNF production in the trigeminal ganglia was then assessed using immunohistochemical and retrograde tracing methods. RESULTS: Reverse transcription-PCR analysis demonstrated that unilateral transection of the mental nerve induced a rapid elevation of BDNF mRNA expression, which was inhibited by the intracerebroventricular administration of L-NAME prior to nerve transection. This effect was observed in both the ipsilateral and contralateral sides to the nerve transection. BDNF immunostaining combined with FluoroGold retrograde tracing revealed two types of BDNF-reactive neurons, FluoroGold-labelled and non-FluoroGold-labelled neurons, in the ipsilateral and contralateral sides of the trigeminal ganglia. BDNF-positive cells were also observed in the trigeminal ganglia of other trigeminal nerve branches. CONCLUSIONS: Unilateral nerve injury upregulates BDNF production in the bilateral trigeminal ganglia by NO-mediated and/or indirect activation of afferent neurons, resulting in contralateral hyperalgesia.

A Case of Cerebral Venous Thrombosis and Deep Venous Thrombosis Due to Hyperthyroidism with Increased Factor VIII Activity.

A 48-year-old woman was admitted to our hospital because of headache and fever. She was diagnosed with aseptic meningitis. Five days later, she had a seizure and developed left hemiparesis. Magnetic resonance imaging showed hyperintensity in the right parietal area on fluid attenuated inversion recovery imaging. She was diagnosed as having cerebral venous thrombosis (CVT) because the suprasagittal sinus was invisible on the venographic studies. Moreover, deep venous thrombosis (DVT) was detected in her left lower extremity. Laboratory findings showed hyperthyroidism and markedly increased factor VIII activity. This is a rare case of concomitant CVT and DVT induced by high factor VIII activity due to hyperthyroidism under the presence of meningitis, an additional risk factor for thrombosis.

Contribution of equilibrative nucleoside transporters 1 and 2 to gemcitabine uptake in pancreatic cancer cells.

Hepatic arterial infusion (HAI) chemotherapy is expected to be a more effective and safer method to treat the hepatic metastasis of pancreatic cancer than intravenous (iv) administration because of higher tumor exposure and lower systemic exposure. To clarify the uptake mechanism of nucleoside anticancer drugs, including gemcitabine (GEM), in pancreatic cancer, we investigated the uptakes of radiolabeled uridine (a general substrate of nucleoside transporters) and GEM in pancreatic cancer cell lines MIA-PaCa2 and As-PC1. Uridine uptake was inhibited by non-labeled GEM and also by S-(4-nitrobenzyl)-6-thioinosine (NBMPR; an inhibitor of equilibrative nucleoside transporters, ENTs) in a concentration-dependent manner, suggesting that ENTs contribute to uridine uptake in pancreatic cancer cells. As for GEM, saturable uptake was mediated by high- and low-affinity components with Km values of micromolar and millimolar orders, respectively. Uptake was inhibited in a concentration-dependent manner by NBMPR and was sodium ion-independent. Moreover, the concentration dependence of uptake in the presence of 0.1 µM NBMPR showed a single low-affinity site. These results indicated that the high- and low-affinity sites correspond to hENT1 and hENT2, respectively. The results indicated that at clinically relevant hepatic concentrations of GEM in GEM-HAI therapy, the metastatic tumor exposure of GEM is predominantly determined by hENT2 under unsaturated conditions, suggesting that hENT2 expression in metastatic tumor would be a candidate biomarker for indicating anticancer therapy with GEM-HAI.

Saturable Hepatic Extraction of Gemcitabine Involves Biphasic Uptake Mediated by Nucleoside Transporters Equilibrative Nucleoside Transporter 1 and 2.

Hepatic arterial infusion (HAI) chemotherapy with gemcitabine (GEM) is expected to be more effective and safer method to treat hepatic metastasis of pancreatic cancer compared with intravenous administration, because it affords higher tumor exposure with lower systemic exposure. Thus, a key issue for dose selection is the saturability of hepatic uptake of GEM. Therefore, we investigated GEM uptake in rat and human isolated hepatocytes. Hepatic GEM uptake involved high- and low-affinity saturable components with Km values of micromolar and millimolar order, respectively. The uptake was inhibited concentration dependently by S-(4-nitrobenzyl)-6-thioinosine (NBMPR) and was sodium-ion-independent, suggesting a contribution of equilibrative nucleoside transporters (ENTs). The concentration dependence of uptake in the presence of 0.1 µM NBMPR showed a single low-affinity binding site. Therefore, the high- and low-affinity sites correspond to ENT1 and ENT2, respectively. Our results indicate hepatic extraction of GEM is predominantly mediated by the low-affinity site (hENT2), and at clinically relevant hepatic concentrations of GEM, hENT2-mediated uptake would not be completely saturated. This is critical for HAI, because saturation of hepatic uptake would result in a marked increase of GEM concentration in the peripheral circulation, abrogating the advantage of HAI over intravenous administration in terms of severe adverse events.