Veno-venous extracorporeal membrane oxygenation in managing acute respiratory distress syndrome associated with hemolytic uremic syndrome and septic shock: a case report.

Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is a rescue therapy for severe respiratory failure in which conventional mechanical ventilation therapy is unsuccessful. Hemolysis during VV-ECMO support arises from multiple factors associated with organ damage and poor outcomes. Therefore, close and prompt monitoring is needed. Hemolytic uremic syndrome (HUS) is characterized by hemolysis, acute renal failure, and thrombocytopenia. Hemolytic features of the disease may complicate VV-ECMO management. A 26-year-old man with a history of cerebral palsy underwent VV-ECMO for acute respiratory distress syndrome (ARDS) due to septic shock caused by bacterial translocation during treatment for HUS. He showed features of hemolysis, with elevated lactate dehydrogenase (LDH), fragmented red blood cells, and low haptoglobin levels. Plasma free hemoglobin was measured daily throughout the whole course of ECMO with levels higher than 10 mg/dL but not exceeding 50 mg/dL. The extracorporeal membrane oxygenation (ECMO) circuit pressures were carefully monitored to ensure the pump generated no excessive negative pressure. The patient was weaned off ECMO on the eleventh day. There have been several cases of VA-ECMO in patients with HUS; however, there is limited literature on VV-ECMO. As the days on VV-ECMO tend to be longer than those on VA-ECMO, features of hemolysis may complicate management. Although HUS did not directly influence the clinical course in the present case, features of hemolysis were continuously observed. This case highlighted the importance of standard ECMO monitoring, especially daily measurement of plasma free hemoglobin.

Association between loss of hypercoagulable phenotype, clinical features and complement pathway consumption in COVID-19.

Background: Coronavirus disease 2019 (COVID-19) features a hypercoagulable state, but therapeutic anticoagulation effectiveness varies with disease severity. We aimed to evaluate the dynamics of the coagulation profile and its association with COVID-19 severity, outcomes, and biomarker trajectories. Methods: This multicenter, prospective, observational study included patients with COVID-19 requiring respiratory support. Rotational thromboelastometry findings were evaluated for coagulation and fibrinolysis status. Hypercoagulable status was defined as supranormal range of maximum clot elasticity in an external pathway. Longitudinal laboratory parameters were collected to characterize the coagulation phenotype. Results: Of 166 patients, 90 (54%) were severely ill at inclusion (invasive mechanical ventilation, 84; extracorporeal membrane oxygenation, 6). Higher maximum elasticity (P=0.02) and lower maximum lysis in the external pathway (P=0.03) were observed in severely ill patients compared with the corresponding values in patients on non-invasive oxygen supplementation. Hypercoagulability components correlated with platelet and fibrinogen levels. Hypercoagulable phenotype was associated with favorable outcomes in severely ill patients, while normocoagulable phenotype was not (median time to recovery, 15 days vs. 27 days, P=0.002), but no significant association was observed in moderately ill patients. In patients with severe COVID-19, lower initial C3, minimum C3, CH50, and greater changes in CH50 were associated with the normocoagulable phenotype. Changes in complement components correlated with dynamics of coagulation markers, hematocrit, and alveolar injury markers. Conclusions: While hypercoagulable states become more evident with increasing severity of respiratory disease in patients with COVID-19, normocoagulable phenotype is associated with triggered by alternative pathway activation and poor outcomes.

High versus low positive end-expiratory pressure setting in patients receiving veno-venous extracorporeal membrane oxygenation support for severe acute respiratory distress syndrome: study protocol for the multicentre, randomised ExPress SAVER Trial.

INTRODUCTION: While limiting the tidal volume to 6 mL/kg during veno-venous extracorporeal membrane oxygenation (V-V ECMO) to ameliorate lung injury in patients with acute respiratory distress syndrome (ARDS) is widely accepted, the best setting for positive end-expiratory pressure (PEEP) is still controversial. This study is being conducted to investigate whether a higher PEEP setting (15 cmH2O) during V-V ECMO can decrease the duration of ECMO support needed in patients with severe ARDS, as compared with a lower PEEP setting. METHODS AND ANALYSIS: The study is an investigator-initiated, multicentre, open-label, two-arm, randomised controlled trial conducted with the participation of 20 intensive care units (ICUs) at academic as well as non-academic hospitals in Japan. The subjects of the study are patients with severe ARDS who require V-V ECMO support. Eligible patients will be randomised equally to the high PEEP group or low PEEP group. Recruitment to the study will continue until a total of 210 patients with ARDS requiring V-V ECMO support have been randomised. In the high PEEP group, PEEP will be set at 15 cmH2O from the start of V-V ECMO until the trials for liberation from V-V ECMO (or until day 28 after the allocation), while in the low PEEP group, the PEEP will be set at 5 cmH2O. Other treatments will be the same in the two groups. The primary endpoint of the study is the number of ECMO-free days until day 28, defined as the length of time (in days) from successful libration from V-V ECMO to day 28. The secondary endpoints are mortality on day 28, in-hospital mortality on day 60, ventilator-free days during the first 60 days and length of ICU stay. ETHICS AND DISSEMINATION: Ethics approval for the trial at all the participating hospitals was obtained on 27 September 2022, by central ethics approval (IRB at Hiroshima University Hospital, C2022-0006). The results of this study will be presented at domestic and international medical congresses, and also published in scientific journals. TRIAL REGISTRATION NUMBER: The Japan Registry of Clinical Trials jRCT1062220062. Registered on 28 September 2022. PROTOCOL VERSION: 28 March 2023, version 4.0.

Early restricted oxygen therapy after resuscitation from cardiac arrest (ER-OXYTRAC): protocol for a stepped-wedge cluster randomised controlled trial.

INTRODUCTION: Cardiac arrest is a critical condition, and patients often experience postcardiac arrest syndrome (PCAS) even after the return of spontaneous circulation (ROSC). Administering a restricted amount of oxygen in the early phase after ROSC has been suggested as a potential therapy for PCAS; however, the optimal target for arterial partial pressure of oxygen or peripheral oxygen saturation (SpO2) to safely and effectively reduce oxygen remains unclear. Therefore, we aimed to validate the efficacy of restricted oxygen treatment with 94%-95% of the target SpO2 during the initial 12 hours after ROSC for patients with PCAS. METHODS AND ANALYSIS: ER-OXYTRAC (early restricted oxygen therapy after resuscitation from cardiac arrest) is a nationwide, multicentre, pragmatic, single-blind, stepped-wedge cluster randomised controlled trial targeting cases of non-traumatic cardiac arrest. This study includes adult patients with out-of-hospital or in-hospital cardiac arrest who achieved ROSC in 39 tertiary centres across Japan, with a target sample size of 1000. Patients whose circulation has returned before hospital arrival and those with cardiac arrest due to intracranial disease or intoxication are excluded. Study participants are assigned to either the restricted oxygen (titration of a fraction of inspired oxygen with 94%-95% of the target SpO2) or the control (98%-100% of the target SpO2) group based on cluster randomisation per institution. The trial intervention continues until 12 hours after ROSC. Other treatments for PCAS, including oxygen administration later than 12 hours, can be determined by the treating physicians. The primary outcome is favourable neurological function, defined as cerebral performance category 1-2 at 90 days after ROSC, to be compared using an intention-to-treat analysis. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board at Keio University School of Medicine (approval number: 20211106). Written informed consent will be obtained from all participants or their legal representatives. Results will be disseminated via publications and presentations. TRIAL REGISTRATION NUMBER: UMIN Clinical Trials Registry (UMIN000046914).

Severe hypocalcemia after denosumab treatment leading to refractory ventricular tachycardia and veno-arterial extracorporeal membrane oxygenation support: a case report.

BACKGROUND: Severe hypocalcemia may lead to life-threatening arrhythmias. Denosumab is an effective treatment for osteoporosis that allows long intervals between doses. However, there is a risk of hypocalcemia in some patients. Due to the long half-life of denosumab, emergency physicians caring for patients presenting with symptoms of hypocalcemia may not be aware of the medication, and adverse effects may last longer. CASE PRESENTATION: A 55-year-old woman with a history of systemic lupus erythematosus (SLE) and anxiety disorder called for an ambulance for symptoms of hyperventilation and muscle cramps. After evaluation at the local hospital, she developed pulseless ventricular tachycardia and was resuscitated by defibrillation by the hospital staff. After conversion to sinus rhythm, she was transported to a tertiary center. Upon arrival, pulseless ventricular tachycardia occurred again, and veno-arterial extracorporeal membrane oxygenation (ECMO) and intra-aortic balloon pumping (IABP) were implemented. Laboratory results showed severe hypocalcemia (corrected calcium level of 5.3 mg/dL) whereupon intravenous calcium supplementation was started. She had received the first dose of denosumab (60 mg) by subcutaneous injection 24 days prior to hospitalization. She was eventually weaned from ECMO and IABP support. CONCLUSION: Cardiac arrest due to hypocalcemia is relatively rare but can be fatal. In the present case, hyperventilation may have acutely exacerbated pre-existing hypocalcemia, leading to ventricular tachycardia. The patient had a slightly decreased serum calcium level prior to denosumab. Close monitoring may be preferable after the primary dose of denosumab in selected patients. Emergency physicians caring for patients who may be suffering from symptoms/signs of hypocalcemia must be mindful of medications that have long half-lives and affect electrolyte balance when treating fatal arrhythmia due to hypocalcemia.

Prognostic Impact of Prehospital Simple Risk Index in Patients With ST-Elevation Myocardial Infarction.

BACKGROUND: The simple risk index recorded in the emergency room (ER-SRI), which is calculated using the formula (heart rate × [age / 10]2) / systolic blood pressure, was shown to be able to stratify the prognosis in ST-elevation myocardial infarction (STEMI) patients. However, the prognostic impact of the prehospital simple risk index (Pre-SRI) remains unknown.Methods and Results: This study enrolled 2,047 STEMI patients from the Mie Acute Coronary Syndrome (ACS) registry. Pre-SRI was calculated using prehospital data and ER-SRI was calculated using emergency room data. The primary endpoint was 30-day all-cause mortality. The cut-off values of Pre-SRI and ER-SRI for predicting 30-day mortality were 34.8 and 34.1, with accuracies of 0.816 and 0.826 based on receiver operating characteristic analyses (P<0.001 for both). There was no difference in the accuracy of the 2 indices. Multivariate Cox regression analysis demonstrated that a High Pre-SRI (≥34) was a significant independent predictor of 30-day mortality. With combined Pre-SRI and ER-SRI assessment, patients with High Pre-SRI/High ER-SRI showed significantly higher mortality than those with High Pre-SRI/Low ER-SRI, Low Pre-SRI/High ER-SRI, and Low Pre-SRI/Low ER-SRI (P<0.001). The addition of High Pre-SRI to High ER-SRI showed incremental prognostic value of the Pre-SRI. CONCLUSIONS: Pre-SRI can identify high-risk STEMI patients at an early stage and combined assessment with Pre-SRI and ER-SRI could be of incremental prognostic value for risk stratification in STEMI patients.

Continuous High Positive-End Expiratory Pressure May Worsen Renal Function in Patients With Acute Respiratory Distress Syndrome: Retrospective Analyses of a Nationwide, Multicenter Observational Study in Japan.

BACKGROUND: Positive end-expiratory pressure (PEEP), especially continuous high PEEP, is thought to be a risk factor for worsening renal function (WRF) due to impaired venous return and the development of renal interstitial edema. In this study, we investigated whether PEEP is a risk factor for WRF in patients with acute respiratory distress syndrome (ARDS), a representative pathology that requires continuous high PEEP for respiratory management. METHODS: We performed retrospective sub-analyses of the Japanese Association for Acute Medicine, a nationwide prospective observational registry of ARDS (FORECAST ARDS registry) prospective multicenter cohort study. WRF was defined on the basis of a worsening renal Sequential Organ Failure Assessment (SOFA) score. We performed univariate and multivariable analyses to identify possible risk factors for WRF, and propensity score analyses to compare the frequency of WRF according to cutoff values for the difference in PEEP between day 1 and day 4. RESULTS: We analyzed 151 cases. Multivariable analysis showed that the difference in PEEP (odds ratio (OR) 1.123 (95% confidence interval (CI) 1.017-1.240), P = 0.022) and male sex (OR 3.287 (95% CI 1.029-10.502), P = 0.045) were risk factors for WRF. Propensity score analysis showed trends towards an increased risk for WRF in each cutoff value for the difference in PEEP: -5 cmH2O (OR 0.389 (95% CI 0.084-1.799), P = 0.229), 0 cmH2O (OR 2.222 (95% CI 0.755-6.540), P = 0.150), and 5 cmH2O (OR 3.277 (95% CI 0.940-11.425), P = 0.065). CONCLUSIONS: This study revealed that the difference in PEEP between days 1 and 4 was positively associated with WRF. However, a significant cutoff value for the difference in PEEP was not determined.

Sequential organ failure assessment score as a predictor of the outcomes of patients hospitalized for classical or exertional heatstroke.

Heatstroke is a life-threatening event that affects people worldwide. Currently, there are no established tools to predict the outcomes of heatstroke. Although the Sequential Organ Failure Assessment (SOFA) score is a promising tool for judging the severity of critically ill patients. Therefore, in this study, we investigated whether the SOFA score could predict the outcome of patients hospitalized with severe heatstroke, including the classical and exertional types, by using data from a Japanese nationwide multicenter observational registry. We performed retrospective subanalyses of the Japanese Association for Acute Medicine heatstroke registry, 2019. Adults with a SOFA score ≥ 1 hospitalized for heatstroke were analyzed. We analyzed data for 225 patients. Univariate and multivariable analyses showed a significant difference in the SOFA score between non-survivors and survivors in classical and exertional heatstroke cases. The area under the receiver operating characteristic curve were 0.863 (classical) and 0.979 (exertional). The sensitivity and specificity of SOFA scores were 50.0% and 97.5% (classical), 66.7% and 97.5% (exertional), respectively, at a cutoff of 12.5, and 35.0% and 98.8% (classical), 33.3% and 100.0% (exertional), respectively, at a cutoff of 13.5. This study revealed that the SOFA score may predict mortality in patients with heatstroke and might be useful for assessing prognosis.

Cardiac Arrest Induced by an Anaphylactic Reaction Associated With the First Dose of Cetuximab.

Cetuximab is a chimeric mouse-human monoclonal antibody biologic used for the treatment of epidermal growth factor receptor-positive colorectal cancer and head and neck cancer. The incidence of severe anaphylaxis after infusion of cetuximab is a rare but fatal complication. Galactose-α-1,3-galactose (α-gal), a side-chain component in cetuximab, can cause the α-gal syndrome, an allergic cross-reaction to the α-gal contained in mammalian muscle. Here, we report a case of cardiac arrest induced by an anaphylactic reaction from cetuximab infusion. After the initial dosing of cetuximab in an outpatient setting, the patient developed sudden cardiac arrest. Flushing of the skin and bronchoconstriction led to the diagnosis of a severe anaphylactic reaction, whereupon he was treated with repeated doses of epinephrine, steroids, and continuous epinephrine infusion. The patient responded well to initial treatment, leading to a full recovery. The patient's history and subsequent blood tests did not show any meat allergies. As an increasing number of patients receive chemotherapy as outpatients, it is important to be aware of the possibility of severe allergic reactions induced by these drugs.

A case of acute bromvalerylurea intoxication that was successfully treated with direct hemoperfusion.

Bromvalerylurea is included in over-the-counter analgesics and is known to cause chronic bromism. Patients can also present acute intoxication because of suicide attempts. The treatment consists of drug cessation and intravenous drip with furosemide. Few reports have described the efficacy of blood purification therapy in a critical case. We report a 21-year-old Japanese woman who was admitted to our hospital in an unconscious state after she had taken 388 tablets of NARON ACE. She was intubated and high flow continuous hemodiafiltration was initiated because her blood pressure remained low, despite continuous intravenous drip infusion. To remove unknown drugs, direct hemoperfusion was performed twice. NARON ACE contains bromvalerylurea, ibuprofen, ethenzamide, and anhydrous caffeine; only the amount of bromvalerylurea was thought to exceed a lethal dose. The plasma concentrations of bromvalerylurea on the first, second, third, and fourth days were 118.9, 45.1, 30.2, and 12.6 µg/mL, respectively. Her level of consciousness improved on the third day and she was extubated. She became stable and was transferred to the psychiatric department to continue medication on day 14. Her clinical course improved, and she was discharged on day 89. In a potentially fatal case, direct hemoperfusion combined with intravenous drip should be considered.

The Evaluation of Helicopter Emergency Medical Services With a Physician for Acute Myocardial Infarction in Japan: A Registry-Based Study of Prognosis and Time Reduction.

OBJECTIVE: The aim of this study was to compare the prognosis and time reduction between helicopter emergency medical services (HEMS) with a physician and ground emergency medical services (GEMS) in acute myocardial infarction (AMI) cases. METHODS: This is a registry-based study of the Japan Helicopter Emergency Medical Service Registry from April 1, 2015, to March 31, 2018. RESULTS: A total of 605 cases of AMI were registered in the HEMS group and 794 cases in the GEMS group. In the cases of non-cardiopulmonary arrest (CPA), the prognosis between HEMS and GEMS did not differ significantly. Regarding the road distance, for ranges of 20 to 40 km and > 40 km, the times from the call to the angiography room were significantly shorter with HEMS than GEMS (median 91 vs. 97 minutes, P = .036 and 101 vs. 132 minutes, P = .002, respectively). In cases of CPA, HEMS had a higher rate of return of spontaneous circulation than GEMS (55.3% vs. 36.8%, P = .038), but HEMS had a lower prognosis than GEMS (22.9% vs. 38.9%, P = .036). CONCLUSION: The present study suggested that HEMS had an advantage in reducing the time to angiography in AMI cases of non-CPA. In cases of CPA, HEMS increased the return of spontaneous circulation without improving the prognosis.

Impact of Helicopter Transport on Reperfusion Times and Long-Term Outcomes in Acute Myocardial Infarction Patients in Rural Areas: A Report From the Mie Acute Coronary Syndrome Registry.

OBJECTIVE: Helicopter emergency medical services (HEMS) are effective for time-sensitive conditions, such as stroke and trauma. However, prognostic data on helicopter transport for acute myocardial infarction (AMI) patients are insufficient. METHODS: We registered 2,681 AMI patients in the Mie Acute Coronary Syndrome Registry and enrolled 163 patients from rural areas to HEMS base hospitals with HEMS or ground emergency medical services (GEMS). They were categorized into 4 groups according to the transportation method for interhospital transfer (direct HEMS: n = 52, direct GEMS: n = 54, interhospital HEMS: n = 32, and interhospital GEMS: n = 25). The primary end point was the emergency medical services (EMS) call-to-balloon time. The secondary end point was 2-year major adverse cardiac and cerebrovascular events. RESULTS: The direct HEMS group was younger than the direct GEMS group (P = .029). The EMS call-to-balloon time was shorter in the direct HEMS and interhospital HEMS groups than in each GEMS group (P = .015 and P = .046). The incidence of 2-year major adverse cardiac and cerebrovascular events tended to be lower in both HEMS groups than in each GEMS group. CONCLUSION: Direct HEMS for AMI in rural areas shortens the time from the EMS call to reperfusion when the transport distance is expected to exceed 30 km, which may result in a better patient prognosis. In addition, prehospital diagnostic modalities, such as 12-lead electrocardiography and echocardiography, may shorten the duration from the EMS call to reperfusion.

Use and effectiveness of a two-level initiation strategy for fixed-dose prothrombin complex concentrate according to the initial international normalized ratio in an emergency department in Japan.

AIM: Prothrombin complex concentrate (PCC) was recently approved for patients on warfarin therapy with international normalized ratios (INRs) exceeding 2 in Japan. However, rapid normalization of INR is necessary even in patients who do not meet the aforementioned criteria. We previously found that a fixed PCC dose of 500 IU is insufficient in some patients with INR elevation but is effective in patients with INR less than 2.5. On the basis of the results, we revised the protocol to administer a PCC dose of 500 IU to patients with INR less than 2.5 or 1,000 IU to patients with higher INRs. This study aimed to validate this revised protocol at an emergency department (ED) in Japan. METHODS: We retrospectively collected data for all patients who received PCC in accordance with the revised protocol at our ED between October 2014 and December 2017 (period B) and compared the findings with those in the previous period (January 2013 to September 2014, period A). RESULTS: In total, 15 and 11 patients received PCC without complications during periods A and B, respectively. All but one patient obeyed the protocol during period B. The average INRs at baseline and within 120 min after PCC infusion were 2.58 and 1.39, respectively, in period A (n = 9), versus 2.54 and 1.28, respectively, in period B (n = 8). Significantly more patients exhibited optimal responses (INR < 1.35) during period B (7/8) than during period A (3/9, P = 0.049). CONCLUSION: Our revised protocol effectively normalized INR.

Veno-arterial extracorporeal membrane oxygenation and targeted temperature management in tricyclic antidepressant-induced cardiac arrest: A case report and literature review.

RATIONALE: Cardiotoxicity is a common cause of death in tricyclic antidepressant (TCA) intoxication. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is effective in critically ill poisoned patients who do not respond to conventional therapies, and targeted temperature management (TTM) is associated with improved neurological outcomes and mortality in comatose out-of-hospital cardiac arrest survivors. However, few reports have documented cases of TCA intoxication that required intensive care, including VA-ECMO or TTM. PATIENT CONCERNS: A 19-year-old Japanese man with a history of depression was brought to our hospital because he was in a comatose state with a generalized seizure. Before admission, he had taken an unknown amount of amitriptyline. DIAGNOSIS: After intubation, the electrocardiogram (ECG) displayed a wide QRS complex tachycardia, and the patient suffered from cardiovascular instability despite intravenous bolus of sodium bicarbonate. At 200 minutes after ingestion, he experienced a TCA-induced cardiac arrest. INTERVENTIONS: We initiated VA-ECMO 240 minutes after ingestion. The hemodynamic status stabilized, and the ECG abnormality improved gradually. In addition, we initiated targeted temperature management (TTM) with a target temperature of 34°C. OUTCOMES: Twenty seven hours after starting the pump, the patient was weaned off the VA-ECMO. After completing the TTM, his mental status improved, and he was extubated on day 5. He was discharged on day 15 without neurological impairment, and the post-discharge course was uneventful. LESSONS: First, VA-ECMO is effective in patients with TCA-induced cardiac arrest. Second, routine ECG screening during VA-ECMO support is useful for assessing the timing to wean off the VA-ECMO, as well as the degree of cardiotoxicity. Third, TTM is safe in comatose survivors of cardiac arrest caused by severe TCA intoxication.

Endovascular Cooling Catheter-Related Thrombosis After Targeted Temperature Management for Out-of-Hospital Cardiac Arrest: A Case Report.

Endovascular cooling catheter-related thrombosis is an under-recognized clinical complication of targeted temperature management (TTM), which is widely used in the treatment of comatose out-of-hospital cardiac arrest survivors. A 16-year-old boy, who survived an out-of-hospital cardiac arrest, underwent TTM with an endovascular cooling system. A target temperature of 34°C was maintained for 24 hours, followed by rewarming at a rate of 0.5°C/12 hours. On day 5, his body temperature rose sharply after the removal of the endovascular cooling catheter. He was diagnosed with pneumonia and methicillin-resistant Staphylococcus aureus bacteremia. Tomography investigations also revealed a marked abnormality in the liver function. On day 7, a large thrombus extending through the right iliac vein and into the inferior vena cava (IVC) was detected. Owing to bacteremia, the IVC filter placement was not indicated, and the thrombus disappeared after intravenous administration of heparin and antithrombin. In addition to the potential risk of catheter-related thrombosis and hypercoagulability in the postcardiac arrest state, acute liver injury and an infective state may contribute to thrombosis.

Invasive Salmonella Enteritidis infection complicated by bacterial meningitis and vertebral osteomyelitis shortly after influenza A infection in an immunocompetent young adult.

Non-typhoidal Salmonella usually manifests as a self-limited acute gastroenteritis but may also cause severe invasive infections almost exclusively among children or immunosuppressed patients. A previously healthy 22-year-old man developed high fever with coma, multiple organ failure and shock. He had visited another hospital complaining of fever 2 days previously and was diagnosed with a common cold. No obvious site of infection was identified by radiology and a rapid test for influenza A virus was positive, indicating possible influenza-associated encephalopathy. However, blood as well as CSF culture yielded Salmonella enterica serotype Enteritidis. Therefore, the patient was considered to be suffering from bacterial meningitis with septic shock concomitant with influenza infection. Antiviral drugs and therapy for septic shock were initiated. He stabilized relatively quickly and his mental status dramatically improved. The patient denied preceding gastrointestinal symptoms, but mentioned that he received positive fecal Salmonella species culture results without medical intervention about 3 months previously. His laboratory values showed marked improvement but his elevated inflammatory markers and fever were sustained. On the 17th day of hospitalization, he complained of back pain and MRI showed lumbar vertebral osteomyelitis. This case indicates that (i) invasive Salmonella infection can be developed even in previously healthy adults; (ii) chronic carriage of Salmonella is a predisposing factor to development of invasive infections, and influenza infection may contribute to such "breakthrough infections"; (iii) attention to manifestation of metastatic extra-intestinal foci even after resolution of sepsis is necessary.

Clinicopathological features of TAFRO syndrome complicated by acquired hemophilia A and development of cardiopulmonary arrest that were successfully treated with VA-ECMO and tocilizumab.

TAFRO syndrome and acquired hemophilia A (AHA) are rare, life-threatening diseases; however, the relationship between these two diseases is unknown. A 25-year-old man was transferred to our hospital because of bleeding tendency accompanied by multiple organ failure with generalized edema, massive pleural effusion, and ascites. He was diagnosed with AHA. Bypass therapy for hemostasis and cyclophosphamide with prednisolone to eradicate possible inhibitors were provided. However, he suffered from cardiopulmonary arrest. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) was initiated as rescue therapy. His hemodynamic status stabilized and he was weaned from VA-ECMO in 1 week. We confirmed normal FVIII activity and disappearance of the inhibitor, and bypass therapy was discontinued. However, generalized edema with massive ascites, pleural effusion, and renal insufficiency persisted. Bone marrow biopsy showed reticulin fibrosis. These symptoms fulfilled the diagnostic criteria of TAFRO syndrome. He received tocilizumab (TCZ) and steroid was tapered off. After four cycles of TCZ, symptoms of TAFRO syndrome gradually improved. To the best of our knowledge, this is the first report of TAFRO syndrome accompanied by AHA with rescue by VA-ECMO. Additionally, AHA and TAFRO syndrome were well controlled by TCZ.

Effects of low-dose tolvaptan on electrolyte abnormality and hemodynamic parameters in a liver cirrhosis-associated portopulmonary hypertension patient: A case report.

The present study reported a case of portopulmonary hypertension (POPH) that was secondary to underlying liver cirrhosis in a 58-year-old woman, who was successfully treated with low-dose tolvaptan. The patient had suffered from refractory peripheral edema and electrolyte abnormalities, including severe hypokalemia, under the combination therapy of sildenafil, ambrisentan, furosemide and spironolactone. Subsequent to the initiation of low-dose tolvaptan at 3.75 mg/day with concurrent de-escalation of the dose of furosemide, the daily urine volume increased, peripheral edema improved and the serum potassium level increased immediately. In addition, plasma renin activity, plasma aldosterone concentration and plasma brain natriuretic peptide level decreased within 1 week after the initiation of tolvaptan therapy. Hemodynamic assessments using a right heart catheter revealed that the pulmonary vascular resistance decreased by ~20%. Finally, chronic combination therapy with spironolactone and low-dose tolvaptan without loop diuretics achieved adequate fluid management. In conclusion, the findings of the present study suggest that low-dose tolvaptan may be a promising therapeutic option for liver cirrhosis-associated POPH in patients with an electrolyte abnormality due to liver cirrhosis and conventional diuretics.

Recurrent SDSE bacteraemia resulting in streptococcal toxic shock syndrome in a patient with Noonan syndrome.

A 19-year-old man with chronic lymphoedema due to Noonan syndrome presented at our hospital with septic shock and pain in his lower leg. Blood cultures were positive for Streptococcus dysgalactiae subsp equisimilis (SDSE), resulting in a diagnosis of cellulitis with toxic involvement. He was treated with ampicillin for 3 weeks. Although he did well for 6 weeks, septic shock recurred. Blood culture again revealed SDSE, with the strain being identical to the first episode, suggesting that this infection had relapsed. He was treated with ampicillin for 6 weeks and prophylactically with trimethoprim-sulfamethoxazole for 12 months. Although SDSE bacteraemia occurs commonly in elderly patients, findings in this patient showed that it can also develop in younger persons with predisposing factors. This case also indicates that SDSE has the potential to recur, despite generally sufficient antibiotic administration, and that patients who experience recurrent episodes may require prolonged treatment with antibiotics, including prophylaxis.