[Cystic duct carcinoma in a patient with a history of cholecystectomy: a case report].

An 83-year-old Japanese man who underwent cholecystectomy for cholecystolithiasis 17 years ago visited our hospital owing to epigastric pain. He was initially diagnosed with choledocholithiasis and acute cholangitis following white blood cell, C-reactive protein, total bilirubin, alkaline phosphatase, and γ-glutamyltranspeptidase level elevations along with common bile duct stones on computed tomography (CT). Moreover, CT, magnetic resonance imaging, endoscopic retrograde cholangiography (ERC), and endoscopic ultrasonography (EUS) also revealed a 2-cm-diameter mass arising from the remnant cystic duct. The cytology of the bile at the time of ERC was not conclusive. However, EUS-assisted fine needle aspiration (EUS-FNA) of the mass confirmed the diagnosis of adenocarcinoma of the remnant cystic duct. The patient underwent extrahepatic bile duct resection. Cystic duct carcinoma following cholecystectomy is rare. We report a case diagnosed by EUS-FNA.

Nationwide Longitudinal Annual Survey of HIV/AIDS Referral Hospitals in Japan From 1999 to 2021: Trend in Non-AIDS-defining Cancers Among Individuals Infected With HIV-1.

BACKGROUND: Non-AIDS-defining cancers (NADCs) in patients infected with HIV have recently attracted attention because of the improved survival of this patient population. To obtain accurate data, a longitudinal study is warranted for the nationwide surveillance of the current status and national trend of NADCs in patients infected with HIV in Japan. SETTING: An annual nationwide surveillance of NADCs in patients infected with HIV-1 in Japan from 1999 to 2021. METHODS: An annual questionnaire was sent to 378 HIV/AIDS referral hospitals across Japan to collect data (clusters of differentiation 4-positive lymphocytes, time of onset, outcomes, and antiretroviral therapy status) of patients diagnosed with any of the NADCs between 1999 and 2021. RESULTS: The response and case-capture rates for the questionnaires in 2021 were 37.8% and 81.2%, respectively. The number of reported NADC cases subsequently increased since the beginning of this study. Evaluation of the case counts of NADCs demonstrated a high incidence of lung, colorectal, gastric, and liver cancers as the top 4 cancers. Pancreatic cancer (0.63), lung cancer (0.49), and leukemia (0.49) had the highest mortality rates among the NADCs. Trends of NADCs regarding transmission routes were maintained over the years in male individuals who have sex with male individuals compared with heterosexual male individuals and female individuals. CONCLUSIONS: We demonstrated an increasing trend in the incidence of NADCs over a period of 23 years in Japan. The current data highlighted the importance of raising awareness regarding cancer management for patients infected with HIV in Japan.

Antimicrobial therapy and outcome of methicillin-resistant Staphylococcus aureus endocarditis: A retrospective multicenter study in Japan.

BACKGROUND: MRSA (methicillin-resistant Staphylococcus aureus)-infective endocarditis (IE) is associated with high morbidity and mortality. This study aimed to assess data from patients with MRSA-IE across multiple facilities in Japan, with a specific focus on antimicrobial therapy and prognosis. METHODS: This retrospective study enrolled patients with a confirmed diagnosis of IE attributed to MRSA, spanning the period from January 2015 to April 2019. RESULTS: Sixty-four patients from 19 centers were included, with a median age of 67 years. The overall mortality rate was 28.1% at 30 days, with an in-hospital mortality of 45.3%. The most frequently chosen initial anti-MRSA agents were glycopeptide in 67.2% of cases. Daptomycin and linezolid were selected as initial therapy in 23.4% and 17.2% of cases, respectively. Approximately 40% of all patients underwent medication changes due to difficulty in controlling infection or drug-related side effects. Significant prognostic factors by multivariable analysis were DIC for 30-day mortality and surgical treatment for 30-day and in-hospital mortality. For vancomycin as initial monotherapy, there was a trend toward a worse prognosis for 30-day and in-hospital mortality (OR, 6.29; 95%CI, 1.00-39.65; p = 0.050, OR, 3.61; 95%CI, 0.93-14.00; p = 0.064). Regarding the choice of initial antibiotic therapy, statistical analysis did not show significant differences in prognosis. CONCLUSION: Glycopeptide and daptomycin were the preferred antibiotics for the initial therapy of MRSA-IE. Antimicrobial regimens were changed for various reasons. Prognosis was not significantly affected by choice of antibiotic therapy (glycopeptide, daptomycin, linezolid), but further studies are needed to determine which antimicrobials are optimal as first-line agents.

Human Vγ9Vδ2 T cells exhibit antifungal activity against Aspergillus fumigatus and other filamentous fungi.

Invasive aspergillosis (IA) and mucormycosis are life-threatening diseases, especially among immunocompromised patients. Drug-resistant Aspergillus fumigatus strains have been isolated worldwide, which can pose a serious clinical problem. As IA mainly occurs in patients with compromised immune systems, the ideal therapeutic approach should aim to bolster the immune system. In this study, we focused on Vγ9Vδ2 T cells that exhibit immune effector functions and examined the possibility of harnessing this unconventional T cell subset as a novel therapeutic modality for IA. A potent antifungal effect was observed when A. fumigatus (Af293) hyphae were challenged by Vγ9Vδ2 T cells derived from peripheral blood. In addition, Vγ9Vδ2 T cells exhibited antifungal activity against hyphae of all Aspergillus spp., Cunninghamella bertholletiae, and Rhizopus microsporus but not against their conidia. Furthermore, Vγ9Vδ2 T cells also exhibited antifungal activity against azole-resistant A. fumigatus, indicating that Vγ9Vδ2 T cells could be used for treating drug-resistant A. fumigatus. The antifungal activity of Vγ9Vδ2 T cells depended on cell-to-cell contact with A. fumigatus hyphae, and degranulation characterized by CD107a mobilization seems essential for this activity against A. fumigatus. Vγ9Vδ2 T cells could be developed as a novel modality for treating IA or mucormycosis. IMPORTANCE: Invasive aspergillosis (IA) and mucormycosis are often resistant to treatment with conventional antifungal agents and have a high mortality rate. Additionally, effective antifungal treatment is hindered by drug toxicity, given that both fungal and human cells are eukaryotic, and antifungal agents are also likely to act on human cells, resulting in adverse effects. Therefore, the development of novel therapeutic agents specifically targeting fungi is challenging. This study demonstrated the antifungal activity of Vγ9Vδ2 T cells against various Aspergillus spp. and several Mucorales in vitro and discussed the mechanism underlying their antifungal activity. We indicate that adoptive immunotherapy using Vγ9Vδ2 T cells may offer a new therapeutic approach to IA.

Risk factor of non-tuberculous Mycobacterium infection in patients with rheumatoid arthritis and other autoimmune diseases receiving biologic agents: A multicenter retrospective study.

BACKGROUND: Evidence regarding the association of the usage of biologic agents (Etanercept, Tocilizumab, adalimumab and so on), such as anti-tumor necrosis factor α, with the incidence and risk factors of non-tuberculous Mycobacteria (NTM) infection is limited. Therefore, this study aimed to investigate the incidence and risk factors of NTM and their associations with biologic agents' usage, and also investigated the potential of Mycobacterium avium complex (MAC) antibodies as a predictor of NTM infection development. METHODS: This retrospective study included 672 patients with autoimmune diseases from four hospitals in Nagasaki, Japan, from January 1, 2011, to June 30, 2019, who fulfilled the inclusion criteria. RESULTS: Of the 672 patients, 9 (1.3%) developed complicated NTM infection, including two with disseminated infection, after the introduction of biologic agents. Of the nine patients, two died due to NTM infection but none tested positive for MAC antibodies prior to initiation of biologic agents. The mortality rate was higher in patients complicated with NTM than without NTM (22.2% vs 2.6%, P = 0.024). The corticosteroids dosage at the time of initiating the biologic agents was significantly higher in the NTM group than in the non-NTM group (median, 17 mg vs 3 mg, P = 0.0038). CONCLUSION: In the patients undergoing therapy with biologic agents, although NTM complication was rare, it could be fatal. In particular, for patients on a relatively high dose corticosteroids, careful observation is essential for identifying NTM complication, even if the MAC antibody test is negative.

Clinical features relating to pneumococcal colony phase variation in hospitalized adults with pneumonia.

Background. Streptococcus pneumoniae is a major causative bacteria of pneumonia and invasive pneumococcal disease (IPD); however, the mechanisms underlying its severity and invasion remain to be defined. Pneumococcal colonies exhibit opaque and transparent opacity phase variations, which have been associated with invasive infections and nasal colonization, respectively, in animal studies. This study evaluated the relationship between the opacity of pneumococcal colonies and the clinical presentation of pneumococcal pneumonia.Methods. This retrospective study included adult patients hospitalized with pneumococcal pneumonia between 2012 and 2019 at four tertiary medical institutions. Pneumococcal strains from lower respiratory tract specimens were determined for their serotypes and microscopic colony opacity, and the association between the opacity phase and the severity of pneumonia was evaluated. Serotypes 3 and 37 with mucoid colony phenotypes were excluded from the study because their colony morphologies were clearly different.Results. A total of 92 patients were included. Most patients were older adults (median age: 72 years) and males (67 %), and 59 % had community-acquired pneumonia. Of the 92 patients, 41 (45 %), 12 (13 %), and 39 (42 %) patients had opaque, transparent, and mixed variants in their pneumococcal colony, respectively. The opaque and non-opaque pneumococcal variants had no statistically significant difference in patient backgrounds. Although the pneumonia severity index score did not differ between the opaque and non-opaque groups, the rate of bacteremia was significantly higher in the opaque group than in the non-opaque group. Serotype distribution was similar between the groups.Conclusions. Opaque pneumococcal variants may cause pneumonia and invasive diseases in humans. This study could help elucidate IPD, and opacity assessment may serve as a predictor for IPD.

Efficacy and safety of lascufloxacin for nursing- and healthcare-associated pneumonia: A single-arm, open-label clinical trial.

BACKGROUND: Nursing- and healthcare-associated pneumonia (NHCAP) constitutes most of the pneumonia in elderly patients including aspiration pneumonia in Japan. Lascufloxacin (LSFX) possesses broad antibacterial activity against respiratory pathogens, such as Streptococcus spp. And anaerobes inside the oral cavity. However, the efficacy and safety of LSFX in NHCAP treatment remains unknown. We aimed to evaluate the efficacy and safety of LSFX tablets in the treatment of patients with NHCAP. METHODS: In this single-arm, open-label, uncontrolled study, LSFX was administered to patients with NHCAP at 24 facilities. The study participants were orally administered 75 mg LSFX once daily for 7 days. The primary endpoint was the clinical efficacy at the time of test of cure (TOC). The secondary endpoints included clinical efficacy at the time of end of treatment (EOT), early clinical efficacy, microbiological efficacy, and safety analysis. RESULT: During the study period, 75 patients provided written informed consent to participate and were included. Finally, 56 and 71 patients were eligible for clinical efficacy and safety analyses, respectively. The median age of the patients was significantly high at 86 years. All patients were classified as having moderate disease severity using the A-DROP scoring system. LSFX tablets demonstrated high efficacy rates of 78.6 % at TOC and 89.3 % at EOT. The risk factors for resistant bacteria or aspiration pneumonia did not affect clinical efficacy. No severe adverse events associated with the study drugs were observed. CONCLUSION: Oral LSFX is an acceptable treatment option for moderate NHCAP in elderly patients who can take oral medications.

Platypnoea-orthodeoxia syndrome in COVID-19 pneumonia patients: An observational study.

This retrospective observational study aimed to assess the clinical characteristics of platypnea-orthodeoxia syndrome in patients with coronavirus disease 2019 (COVID-19) treated using mechanical ventilation or high-flow nasal canula. We analyzed 42 consecutive patients with COVID-19 from January 2020 to March 2022. The primary outcomes were the incidence of platypnea-orthodeoxia syndrome, the time with required long-term oxygen therapy, and short-term prognosis. Additionally, we examined the relationships between platypnea-orthodeoxia syndrome and COVID-19 severity, the time with long-term oxygen therapy, and short-term prognosis. Of the 42 included patients, 15 (35.7 %) had platypnea-orthodeoxia syndrome. Although mortality was not significantly different between both groups, the oxygen withdrawal rate in the platypnea-orthodeoxia syndrome group was significantly lower than that in the group without this syndrome. Clinical staff should be aware of the possibility of platypnea-orthodeoxia syndrome during positional changes in patients with COVID-19. Recognizing POS can improve early detection, countermeasures, and safety during physiotherapy.

The prognostic factors for cryptococcal meningitis in non-human immunodeficiency virus patients: An observational study using nationwide database.

BACKGROUND: Cryptococcal meningitis (CM) is an invasive fungal infection with a poor prognosis that often occurs in both healthy individuals and compromised hosts, such as patients infected with human immunodeficiency virus (HIV). Unlike CM in HIV patients, evidence regarding CM in non-HIV patients is limited to small retrospective studies. OBJECTIVE: To identify the pretreatment prognostic factors for CM in non-HIV patients. METHODS: We conducted a large retrospective analysis of CM in non-HIV patients using data from a nationwide Japanese database. The study included hospitalized patients diagnosed with CM between 1 April 2010 and 31 March 2017. All-cause mortality was compared between patients with CM with and without HIV infection. Poor diagnostic factors were analysed in the non-HIV CM group. RESULTS: Overall, 533 (64 HIV and 469 non-HIV) patients met the criteria. The mortality rate at 90 days was significantly lower in the HIV group (6.3% vs. 25.4% p = .0002). In a logistic regression analysis of the non-HIV group, age ≥ 65 y (odds ratio [OR] 2.37, 95% CI 1.17-4.78), impaired consciousness (Japan Coma Scale ≥1) (OR 2.25, 95% CI 1.29-3.93), haemodialysis (OR 3.53, 95% CI 1.12-11.20) and previous corticosteroid usage (OR 2.40, 95% CI 1.37-4.19) were associated with poor prognosis at 30 days after diagnosis. CONCLUSION: More caution is suggested when treating non-HIV with CM in older patients with impaired consciousness, previous corticosteroid usage and haemodialysis.

Efficacy of Intrathecal Isoniazid and Steroid Therapy in Refractory Tuberculous Meningitis.

Tuberculous meningitis is an infectious disease with high mortality. Literature describing intrathecal therapy for tuberculous meningitis is scarce. We herein report a case of refractory tuberculous meningitis in a 52-year-old woman with underlying neuropsychiatric systemic lupus erythematosus. Despite systemic treatment with anti-tuberculosis drugs and dexamethasone, her meningeal irritation deteriorated. Intrathecal isoniazid and prednisolone administration was therefore initiated, and the symptoms of severe meningeal irritation improved along with head magnetic resonance imaging and cerebrospinal fluid findings. This case report highlights the efficacy of intrathecal isoniazid and steroid injections for refractory tuberculous meningitis, particularly in patients with severe meningeal irritation.

Rapid increase in salivary IgA and broad recognition of spike protein following SARS-CoV-2 vaccination.

Saliva is a key component of mucosal immunity, which protects the oral cavity from viral infections. However, salivary immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in terms of immunoglobulin dynamics and recognition, have not been investigated sufficiently. In this study, saliva samples were collected from individuals that received SARS-CoV-2 vaccine, and immunoglobulin G (IgG), IgM, and IgA against whole spike protein and S1 protein were measured. IgA against whole spike protein increased significantly following vaccination, while IgA against S1 protein did not. Of note, the IgA response was evident two weeks after the first vaccine dose and continued to rise thereafter. On the contrary, IgG antibodies against S1 increased significantly at four weeks after vaccination. These results reveal the dynamics and recognition antigens of immunoglobulins in saliva, indicating the function of IgA in the mucosal immune system. These findings may pave the way for further studies on mucosal immune response induced by vaccination.

The evaluation of a rapid microfluidic immunofluorescence antigen test in detecting the infectiousness of COVID-19 patients.

BACKGROUND: A test-based strategy against coronavirus disease 2019 (COVID-19) is one of the measures to assess the need for isolation and prevention of infection. However, testing with high sensitivity methods, such as quantitative RT-PCR, leads to unnecessary isolation, whereas the lateral flow antigen test shows low sensitivity and false negative results. The purpose of this study was to evaluate the performance of the LumiraDx SARS-CoV-2 Ag test (Lumira Ag), a rapid microfluidic immunofluorescence method, in assessing infectivity. METHODS: This study was performed from March 2022 to July 2022. A pair of nasopharyngeal swab samples were obtained from each patient with mild COVID-19. One swab was used for Lumira Ag testing, and the other for quantitative RT-PCR testing and virus culture. RESULTS: A total of 84 patients were included in the study. Among them, PCR, Lumira Ag test, and virus culture indicated positivity for 82, 66, and 24 patients, respectively. When comparing the Lumira Ag test to virus culture, its sensitivity was 100.0% (24/24), specificity, 30.0% (18/60); positive predictive value, 36.3% (24/66); and negative predictive value (NPV), 100.0% (18/18). The positive sample for virus culture was observed until the ninth day from the onset of symptoms, while the Lumira Ag test was observed until day 11. CONCLUSIONS: The Lumira Ag test showed high sensitivity and NPV (100% each) compared to virus culture. A test-based strategy using the Lumira Ag test can effectively exclude COVID-19 infectiousness.

Invasive Malassezia Infections.

The Malassezia species are dimorphic fungi that require lipids such as olive oil for their growth. They are constituents of the normal human skin microbiota and can affix to the host or other surfaces through the establishment of biofilms. Malassezia species are accountable for superficial mycoses like folliculitis. Additionally, they are capable of causing invasive infections, such as of the bloodstream, in neonates and immunocompromised patients, albeit infrequently. Catheter-associated bloodstream infections in neonates are the most commonly reported invasive cases. Remarkably, unlike other invasive fungal infections, neutropenia and the use of broad-spectrum antibiotics do not seem to contribute to the risk of invasive Malassezia infections. Nosocomial outbreaks of Malassezia infections have been reported. While most cases of invasive Malassezia infection are fungemia, they seldom give rise to disseminated lesions in various organs. The diagnosis can be confirmed by the visualization of characteristic yeasts through histologic or cytologic examination of a biopsy or needle aspiration specimen, or via positive culture results from sterile sites. The prognosis for invasive Malassezia infection is generally favorable, with few reports of treatment failure. Nevertheless, due to the limited number of cases, evidence-based treatment recommendations are wanting. Management of invasive Malassezia infections linked to central venous catheters includes removal of the catheter, cessation of intravenous lipid emulsion, and intravenous administration of appropriate antifungal agents.

Isolation of Aspergillus udagawae in Canaliculitis: A Case Report.

Aspergillus udagawae is a cryptic species of Aspergillus section Fumigati. Here, we report a case of canaliculitis with isolated A. udagawae. Fungal canaliculitis is a rare lacrimal disease, and its clinical features are poorly understood. The causative fungus was initially misclassified as Aspergillus thermomutatus by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) but was finally identified as A. udagawae by ß-tubulin genetic analysis. The patient showed rapid improvement and did not experience relapse after drainage alone, without antifungal therapy. A. udagawae has low virulence, which may be related to the minimally invasive nature of the infection.

Adherence to recommended vaccination policies for pre- and post-solid organ transplantation patients: A national questionnaire survey in Japan.

BACKGROUND: Pre-transplant vaccination is recommended for patients undergoing solid organ transplantation (SOT). While appropriate vaccination protocols are implemented at some facilities, transplantation is sometimes performed with inadequate preoperative vaccine management. Vaccination rates vary across facilities, but those of SOT centers in Japan have never been investigated. This study aimed to conduct a nationwide questionnaire survey to assess pre- and post-transplant vaccination policies among SOT facilities in Japan. METHODS: The survey was conducted from September to November 2022. All registered (n = 221) solid organ (namely, the lungs, liver, kidneys, pancreas, heart, and small intestine) transplant facilities were asked to complete a web-based survey. RESULTS: The survey response rate was 70.2 %. Live and inactivated vaccines were recommended at 64.9 % and 68.9 % of the responding facilities, respectively. The following vaccines were incorporated into the vaccination protocols of facilities: pneumococcal vaccine, 31.7 % (13-valent pneumococcal conjugate vaccine) and 65.4 % (23-valent pneumococcal polysaccharide vaccine); hepatitis B virus vaccine, 67.3 %; severe acute respiratory syndrome coronavirus 2 vaccine, 73.1 %; influenza vaccine, 73.1 %; and zoster vaccines, 23.1 %. The reasons for unresponsiveness to vaccinations included inadequate time before transplantation (60.3 %), cost burden (41.1 %), high number of vaccinations (21.9 %), no recognition of the need for vaccination (17.9 %), and the requirement to explain the need for vaccination (15.2 %). CONCLUSIONS: Our study revealed gaps in vaccination practices across nationwide facilities in Japan. The findings indicate the importance of promoting scheduled efficiency and encouraging the national health system to reduce vaccine costs with the support of public subsidies.

Serum Cytokine Changes in a Patient with Chronic Pulmonary Aspergillosis Overlapping with Allergic Bronchopulmonary Aspergillosis: A Case Report.

Allergic bronchopulmonary aspergillosis (ABPA) and chronic pulmonary aspergillosis (CPA) are diseases caused by Aspergillus infection, and CPA can develop from ABPA in some cases. We herein report a patient with CPA overlapping with ABPA. Serum cytokine levels were evaluated at 4 time points: the ABPA diagnosis, CPA diagnosis, 6 months after the start of voriconazole (VRCZ), and 12 months after re-administration of VRCZ. Interleukin (IL)-13 levels decreased upon glucocorticoid treatment, whereas IL-25 and IL-33 levels decreased rapidly with the initiation of antifungals. Early antifungal therapy may be important to control disease progression and prevent CPA overlap.

Prognostic Association of Liposomal Amphotericin B Doses Above 5†mg/kg/d in Mucormycosis: A Nationwide Epidemiologic and Treatment Analysis in Japan.

Background: Mucormycosis is a potentially fatal fungal infection, and there is limited information on its precise epidemiology and treatment practices, including the optimal dosage of liposomal amphotericin B. Methods: A retrospective, multicenter, nationwide analysis of 82 proven and probable cases of mucormycosis was performed. Cases between 2015 and 2022 were collected from 51 hospitals in Japan by hematologists and infectious disease specialists. The study included the epidemiology, treatment details, and association between the dose of liposomal amphotericin B and the outcome. Results: The lungs were the most commonly involved organ (70.7% of cases), and 35.4% of patients had disseminated disease. Rhizopus spp., Cunninghamella spp., and Mucor spp. were the most common organisms. Mortality at 4 weeks was 41.5%. The survivors had a shorter duration of neutropenia (P = .006) and less persistent hyperglycemia (P = .023). The site of infection and species of Mucorales had no detectable effect on survival. Survival did not differ between patients receiving liposomal amphotericin B at 5 mg/kg/d relative to those receiving >5 mg/kg/d (P = .625). Using Cox proportional hazards models and adjusting for confounders, the hazard ratio for the influence of >5 mg/kg/d liposomal amphotericin B on 4-week survival was 0.86 (95% CI, 0.28-2.68; P = .796) compared with 5 mg/kg/d. Conclusions: This study provides important insights into the precise epidemiology and treatment practices of mucormycosis. Treatment with liposomal amphotericin B at doses higher than 5 mg/kg/d did not improve outcomes relative to 5 mg/kg/d.

Safety and efficacy of 5-aminolevulinic acid phosphate/iron in mild-to-moderate coronavirus disease 2019: A randomized exploratory phase II trial.

BACKGROUND: 5-aminolevulinic acid (5-ALA), a natural amino acid that is marketed alongside sodium ferrous citrate (SFC) as a functional food, blocks severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proliferation in vitro and exerts anti-inflammatory effects. In this phase II open-label, prospective, parallel-group, randomized trial, we aimed to evaluate the safety and efficacy of 5-ALA in patients with mild-to-moderate coronavirus disease 2019. METHODS: This trial was conducted in patients receiving 5-ALA/SFC (250/145 mg) orally thrice daily for 7 days, followed by 5-ALA/SFC (150/87 mg) orally thrice daily for 7 days. The primary endpoints were changes in SARS-CoV-2 viral load, clinical symptom scores, and 5-ALA/SFC safety (adverse events [AE] and changes in laboratory values and vital signs). RESULTS: A total of 50 patients were enrolled from 8 institutions in Japan. The change in SARS-CoV-2 viral load from baseline was not significantly different between the 5-ALA/SFC (n = 24) and control (n = 26) groups. The duration to improvement was shorter in the 5-ALA/SFC group than in the control group, although the difference was not significant. The 5-ALA/SFC group exhibited faster improvement rates in "taste abnormality," "cough," "lethargy," and "no appetite" than the control group. Eight AEs were observed in the 5-ALA/SFC group, with 22.7% of patients experiencing gastrointestinal symptoms (decreased appetite, constipation, and vomiting). AEs occurred with 750/435 mg/day in 25.0% of patients in the first phase and with 450/261 mg/day of 5-ALA/SFC in 6.3% of patients in the second phase. CONCLUSION: 5-ALA/SFC improved some symptoms but did not influence the SARS-CoV-2 viral load or clinical symptom scores over 14 days. The safety of 5-ALA/SFC in this study was acceptable. Further evaluation using a larger sample size or modified method is warranted.

Venoarterial extracorporeal membrane oxygenation for group B streptococcal toxic shock syndrome: A case report and literature review.

RATIONALE: Streptococcal toxic shock syndrome (STSS) rapidly leads to refractory shock and multiple organ failure. The mortality rate among patients with STSS is 40%; however, most deaths occur within a few days of onset. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) may help avoid acute death in adult patients with STSS. However, the effectiveness of VA-ECMO is unclear. In this study, we report a case of group B STSS, which was successfully treated with VA-ECMO despite cardiopulmonary arrest (CPA) owing to rapidly progressive refractory shock. PATIENT CONCERNS: A 60-year-old woman was hospitalized because of diarrhea and electrolyte abnormalities owing to chemoradiation therapy for rectal cancer. A sudden deterioration of her condition led to CPA. Conventional cardiopulmonary resuscitation was immediately performed but was ineffective. Therefore, VA-ECMO was initiated. Contrast-enhanced computed tomography revealed duodenal perforation. Hence, septic shock owing to peritonitis was diagnosed, and emergency surgery was performed under VA-ECMO. However, the patient had progressive multiple organ failure and required organ support therapy in the intensive care unit (ICU). DIAGNOSES: On day 2 in the ICU, blood and ascites fluid culture tests revealed beta-hemolytic streptococci, and the patient was finally diagnosed as having STSS caused by Streptococcus agalactiae. INTERVENTIONS: Clindamycin was added to meropenem, vancomycin, and micafungin, which had been administered since the sudden deterioration. In addition, VA-ECMO, mechanical ventilation, blood purification therapy, and treatment for disseminated intravascular coagulation were continued. OUTCOMES: Thereafter, hemodynamics improved rapidly, and the patient was weaned off VA-ECMO on day 5 of ICU admission. She was transferred to a general ward on day 22 in the ICU. LESSONS: In patients with fatal STSS and rapid progressive refractory shock or CPA, VA-ECMO may help to avoid acute death and improve prognosis by ameliorating tissue oxygenation and providing extra time to treat invasive streptococcal infection.