Current perspectives of viral hepatitis.

Viral hepatitis represents a major danger to public health, and is a globally leading cause of death. The five liver-specific viruses: Hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus, and hepatitis E virus, each have their own unique epidemiology, structural biology, transmission, endemic patterns, risk of liver complications, and response to antiviral therapies. There remain few options for treatment, in spite of the increasing prevalence of viral-hepatitis-caused liver disease. Furthermore, chronic viral hepatitis is a leading worldwide cause of both liver-related morbidity and mortality, even though effective treatments are available that could reduce or prevent most patients' complications. In 2016, the World Health Organization released its plan to eliminate viral hepatitis as a public health threat by the year 2030, along with a discussion of current gaps and prospects for both regional and global eradication of viral hepatitis. Today, treatment is sufficiently able to prevent the disease from reaching advanced phases. However, future therapies must be extremely safe, and should ideally limit the period of treatment necessary. A better understanding of pathogenesis will prove beneficial in the development of potential treatment strategies targeting infections by viral hepatitis. This review aims to summarize the current state of knowledge on each type of viral hepatitis, together with major innovations.

Secondary pulmonary infection by Fusarium solani and Aspergillus niger during systemic steroid treatment for COVID-19: A case report.

BACKGROUND: Coronavirus disease 2019 (COVID-19)-associated invasive pulmonary aspergillosis presents a diagnostic challenge due to its non-specific clinical/ imaging features, as well as the fact that the proposed clinically diagnostic algorithms do not necessarily apply to COVID-19 patients. In addition, Fusarium spp. is a rare cause of opportunistic life-threatening fungal infections. Disseminated Fusarium infection in an immunocompromised host is intractable, with a high likelihood of resulting mortality. To our knowledge, this is the first case of secondary pulmonary infection by Fusarium solani (F. solani) and Aspergillus niger (A. niger) during systemic steroid treatment for COVID-19. CASE SUMMARY: A 62-year-old male was transported to our hospital by ambulance with a complaint of fever and dyspnea. We established a diagnosis of pneumococcal pneumonia, complicated with COVID-19 and septic shock, together with acute renal failure. He was admitted to the intensive care unit, to be treated with piperacillin/tazobactam, vancomycin, and 6.6 mg per day of dexamethasone sodium phosphate, along with noradrenaline as a vasopressor, ventilator management, and continuous hemodiafiltration. His condition improved, and we finished the vasopressor on the fifth hospital day. We administered dexamethasone for ten days, and finished the course of treatment. On the eleventh day, patient respiratory deterioration was observed, and a computed tomography scan showed an exacerbation of bilateral ground-glass-opacity-like consolidation, together with newly appeared cavitary lesions in the lung. we changed antibiotics to meropenem plus vancomycin. In addition, a fungal infection was considered as a possibility based on microscopic findings of sputum, and we began coadministration of voriconazole. However, the pneumonia worsened, and the patient died on the seventeenth day of illness. Later, F. solani and A. niger were identified from sputum collected on the twelfth day. It was believed that he developed a cell-mediated immune deficiency during COVID-19 treatment, which led to the complication of pneumonia caused by the above-mentioned fungi, contributing to his death. CONCLUSION: Because early initiation of intense antifungal therapy offers the best chance for survival in pulmonary fusariosis, computed tomography scans and appropriate microbiologic investigations should be obtained for severely immunocompromised patients.

Penile and scrotal strangulation by stainless steel rings in an human immunodeficiency virus positive man: A case report.

BACKGROUND: Penoscrotal constriction devices are either used as autoerotic stimuli or to increase sexual pleasure or performance by maintaining an erection for a longer period, and a variety of metallic and non-metallic objects are used. On the other hand, penile strangulation is a rare urologic emergency that requires prompt evaluation and intervention to prevent long-term complications. The goal of treating penile incarceration is to remove the foreign object as soon as possible. On the other hand, removal can be very challenging, and often requires resourcefulness and a multidisciplinary approach. CASE SUMMARY: A 47-year-old man who has sex with men was transferred to our hospital for persistent phallodynia and scrotal pain, accompanying swelling due to strangulation by stainless steel rings. His medical history included acquired immunodeficiency syndrome. One day prior, he had put three stainless steel rings on his penis and scrotum before sexual intercourse. After sexual intercourse, he was unable to remove them, due to swelling of his penis and scrotum. The swelling persisted, and he felt pain in the affected area the next day, then he was transferred to our hospital by ambulance. The emergency department found that his penis and scrotum were markedly engorged and swollen. We established a diagnosis of penile and scrotal strangulation by stainless steel rings. We unsuccessfully attempted to cut the rings using a cutter, then requested a rescue team via emergency medical service. They cut through each ring in two places, using an electric-powered angle grinder, and successfully removed all of the pieces. Finally, he was discharged and went home. CONCLUSION: We report the first case of penile and scrotal strangulation by stainless steel rings in an human immunodeficiency virus positive person.

Preferential B cell differentiation by combined immune checkpoint blockade for renal cell carcinoma is associated with clinical response and autoimmune reactions.

Combined immune checkpoint blockade (ICB) is effective therapy for renal cell carcinoma (RCC). However, the dynamic changes in circulating B cells induced by combined ICB have not been clarified. The present study prospectively examined 22 patients scheduled to receive ICB for unresectable or metastatic RCC between March 2018 and August 2021. Eleven patients received combined therapy with anti-PD-1 (nivolumab) and anti-CTLA-4 (ipilimumab), and the other 11 patients received nivolumab monotherapy. Comprehensive phenotypes of circulating immune cells obtained prior to and after ICB therapy were analyzed by flow cytometry. Although the proportion of naïve B cells among total B cells was significantly decreased, that of switched memory B cells was significantly increased after combined therapy. In responders, the proportion of B cells among peripheral blood mononuclear cells was significantly higher prior to ICB therapy, and the proportion of switched memory B cells among total B cells tended to increase after ICB therapy. Of note, the proportion of plasmablasts among total B cells was significantly increased after ICB therapy in patients who developed severe immune-related adverse events (irAEs), and the proportion of B cells among peripheral blood decreased significantly. Furthermore, in four of five patients who developed immune-related hypophysitis following combined therapy, anti-pituitary antibody was detected in the serum. These results suggested that immune-related hypophysitis was closely related to the increase in circulating plasmablasts. Collectively, this study suggests that combined ICB promotes the differentiation of B cell populations, which is associated with efficient tumor suppression and development of irAEs.

High doses of dextromethorphan induced shock and convulsions in a 19-year-old female: A case report.

BACKGROUND: Dextromethorphan is a prevalent antitussive agent that can be easily obtained as an over-the-counter medication. There has been a growing number of reported cases of toxicity in recent years. Generally, there are numerous instances of mild symptoms, with only a limited number of reports of severe cases necessitating intensive care. We presented the case of a female who ingested 111 tablets of dextromethorphan, leading to shock and convulsions and requiring intensive care that ultimately saved her life. CASE SUMMARY: A 19-year-old female was admitted to our hospital via ambulance, having overdosed on 111 tablets of dextromethorphan (15 mg) obtained through an online importer in a suicide attempt. The patient had a history of drug abuse and multiple self-inflicted injuries. At the time of admission, she exhibited symptoms of shock and altered consciousness. However, upon arrival at the hospital, the patient experienced recurrent generalized clonic convulsions and status epilepticus, necessitating tracheal intubation. The convulsions were determined to have been caused by decreased cerebral perfusion pressure secondary to shock, and noradrenaline was administered as a vasopressor. Gastric lavage and activated charcoal were also administered after intubation. Through systemic management in the intensive care unit, the patient's condition stabilized, and the need for vasopressors ceased. The patient regained consciousness and was extubated. The patient was subsequently transferred to a psychiatric facility, as suicidal ideation persisted. CONCLUSION: We report the first case of shock caused by an overdose of dextromethorphan.

Hemorrhagic shock due to submucosal esophageal hematoma along with mallory-weiss syndrome: A case report.

BACKGROUND: Esophageal submucosal hematoma is a rare condition. Although the exact etiology remains uncertain, vessel fragility with external factors is believed to have led to submucosal bleeding and hematoma formation; the vessel was ruptured by a sudden increase in pressure due to nausea, and the hematoma was enlarged by antiplatelet or anticoagulant therapy. Serious conditions are rare, with a better prognosis. We present the first known case of submucosal esophageal hematoma-subsequent hemorrhagic shock due to Mallory-Weiss syndrome. CASE SUMMARY: A 73-year-old female underwent endovascular treatment for an unruptured cerebral aneurysm. The patient received aspirin and clopidogrel before surgery and heparin during surgery, and was well during the surgery. Several hours after returning to the ICU, she complained of chest discomfort, vomited 500 mL of fresh blood, and entered hemorrhagic shock. Esophageal submucosal hematoma with Mallory-Weiss syndrome was diagnosed through an endoscopic examination and computed tomography. In addition to a massive fluid and erythrocyte transfusion, we performed a temporary compression for hemostasis with a Sengstaken-Blakemore (S-B) tube. Afterwards, she became hemodynamically stable. On postoperative day 1, we performed an upper gastrointestinal endoscopy and confirmed no expansion of the hematoma nor any recurring bleeding; therefore, we removed the S-B tube and clipped the gastric mucosal laceration at the esophagogastric junction. We started oral intake on postoperative day 10. The patient made steady progress, and was discharged on postoperative day 33. CONCLUSION: We present the first known case of submucosal esophageal hematoma subsequent hemorrhagic shock due to Mallory-Weiss syndrome.

Obligate aerobic, gram-positive, weak acid-fast, nonmotile bacilli, Tsukamurella tyrosinosolvens: Minireview of a rare opportunistic pathogen.

Tsukamurella species are obligate aerobic, gram-positive, weak acid-fast, nonmotile bacilli. They are found in various environments, such as soil, water, sludge, and petroleum reservoir wastewater, and belong to the order Actinomycetales. In 2016, there was a reclassification of species within the genus Tsukamurella, merging the species Tsukamurella tyrosinosolvens (T. tyrosinosolvens) and Tsukamurella carboxydivorans. Tsukamurella species are clinically considered to be a rare opportunistic pathogen, because most reported cases have been related to bacteremia and intravascular prosthetic devices and immunosuppression. To date, it has been isolated only from human specimens, and has always been associated with clinical disease; human infections are very rare. Reported infections have included pneumonia, brain abscesses, catheter-related bloodstream infections, ocular infections, bacteremia, and sepsis presenting with septic pulmonary emboli in patients who are immunocompromised. To date, there is no commercially available test for identification. On the other hand, sequence-based identification, including matrix-assisted laser desorption ionization time-of-flight mass spectrometry, is an alternative method for identifying clinical isolates that are either slow growers or difficult to identify through biochemical profiling. The golden standards for diagnosis and optimal management still remain to be determined. However, newer molecular biological techniques can provide accurate identification, and contribute to the appropriate selection of definitive therapy for infections caused by this organism. Combinations of several antimicrobial agents have been proposed for treatment, though the length of treatment for infections has yet to be determined, and should be individualized according to clinical response. Immunocompromised patients often experience severe cases due to infection, and life-threatening T. tyrosinosolvens events associated with dissemination and/or failure of source control have occurred. Favorable prognoses can be achieved through earlier identification of the cause of infection, as well as successful management, including appropriate antibiotic therapy together with source control. Further analyses of similar cases are required to establish the most adequate diagnostic methods and treatment regimens for infections.

ST-Elevation Acute Myocardial Infarction in a Young Man.

Acute myocardial infarction (AMI) in young patients is very rare, but the incidence has increased over years past at younger ages, likely due to the presence of multiple risk factors. We present the first known case of ST-elevation AMI (STEMI) in a young man. A 22-year-old Japanese man was transferred to our hospital due to suddenly occurred anterior chest pain. An electrocardiogram revealed ST elevation in anteroseptal leads together with reciprocal ST depression in inferior leads. An emergency coronary angiogram was performed, revealing a 100% occlusion at segment 6 of the coronary artery and we established a diagnosis of STEMI. The lesion was expanded to 0% stenosis through plain old balloon angioplasty, after which a third-generation drug-eluting stent was installed there. Afterwards, the patient was discharged on day 17. In this case, a combination of mild six risk factors plus family history of hypertension might lead to this atypical event.

How Many Clinical Trials Exist that Have Adopted Selective Safety Data Collection? NEJM Literature Search Results: The Possibility of Harmonizing the ICH E19 Guideline.

BACKGROUND: The selective safety data collection (SSDC) proposed in The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use E19 guideline is a more selective approach to collect safety data of medicinal products with well-characterized safety profiles. There has been no systematic survey of the implementation status of SSDCs. METHODS: A literature search was conducted on clinical trials using SSDC published in The New England Journal of Medicine from February 1, 2016, to December 31, 2019. By reviewing the retrieved texts, protocols, and statistical analysis plans, we identified the method of safety data collection and evaluated whether each trial adopted SSDC. RESULTS: Of the 459 trials of medicinal products searched, 44 clinical trials adopted SSDC. The common objectives of these studies were "to study additional endpoints" (31 trials, 70.5%) and "new indications of approved drugs" (8 trials, 18.2%). Participant number was more than 1000 in 33 trials (75.0%). Most trials adopted SSDC for the entire study population throughout the trial period. Death and serious adverse events (SAEs) were recorded in all trials. Twenty-nine (66.6%) recorded death, SAE, and AE leading to drug discontinuation, which were specified in the E19 draft guideline as the data that should be collected under all circumstances. CONCLUSION: There have already been cases where SSDC was used in clinical trials for regulatory application. It is desirable that the E19 guideline will harmonize the method for implementation of SSDC, making SSDC more common as an option for clinical trial design.

Estimation of a Suitable Number of Patients for Selective Safety Data Collection (ICH E19 Draft Guideline): When is the Safety Profile of a Drug Well Characterized?

PURPOSE: We propose methods to estimate a suitable number of patients for implementing selective safety data collection (SSDC) in clinical investigations based on a confidence interval of the incidence rate or risk difference using Monte Carlo simulation. METHODS: The incidence rates and risk differences of adverse events (AEs) were based on the safety outcome measures. A suitable number of patients for implementing SSDC was estimated based on the probability that the half-width of the two-sided 95% confidence interval of incidence rate or risk difference was equal to or less than a pre-specified cut-off value (0.5-3.0%). Monte Carlo simulation was used to estimate the suitable number of patients at probabilities of 70%, 80%, and 90%. The applicability of our proposed method for estimating a suitable number of patients for SSDC implementation was confirmed based on the incidence rates or risk differences from actual clinical trial data for panitumumab. RESULTS: We demonstrated the performance of our proposed method in estimating a suitable number of patients to implement SSDC in several situations. Furthermore, according to the safety datasets of three phase III clinical trials, the number of suitable patients for implementing SSDC using incidence rates or risk differences of common AEs with panitumumab could confirm the applicability of our proposed method. CONCLUSION: A suitable number of patients estimated based on our proposed method may be one of the foundations for implementing SSDC, as additional data accrual may not impact the precision of the estimates of the frequency of common AEs.

Retrospective Study of Cisplatin/Carboplatin, 5-Fluorouracil Plus Cetuximab (EXTREME) for Advanced-stage Salivary Gland Cancer.

BACKGROUND/AIM: Surgery remains the standard treatment for salivary gland carcinoma (SGC). Our study investigated the association between epidermal growth factor receptor (EGFR) status in recurrent/metastatic SGC and the effectiveness of treatment with cisplatin/carboplatin and 5-fluorouracil plus cetuximab (EXTREME). PATIENTS AND METHODS: We retrospectively collected 19 SGCs from patients treated with the EXTREME regimen. After analyzing EGFR expression and gene copy number gain, we evaluated the correlation between EGFR status and clinicopathological factors and prognosis. RESULTS: EGFR overexpression was detected in 77.8% cases, but not statistically associated with clinicopathological factors or prognosis. EGFR gene copy number gain was detected in 16.7% cases, and statistically positively correlated with lymph node metastasis (p=0.0291). The best overall response was partial response in two cases, stable disease in 15, and progressive disease in one case. The EXTREME regimen was discontinued in all cases. CONCLUSION: Our results suggest that SGCs are positive for EGFR protein expression but the response rate to the EXTREME regimen was unremarkable.

Macrophages are primed to transdifferentiate into fibroblasts in malignant ascites and pleural effusions.

Cancer-associated fibroblasts (CAFs) play an important role in cancer progression. However, the origin of CAFs remains unclear. This study shows that macrophages in malignant ascites and pleural effusions (cavity fluid-associated macrophages: CAMs) transdifferentiate into fibroblast-like cells. CAMs obtained from gastrointestinal cancer patients were sorted by flow cytometry and cultured in vitro. CD45+CD14+ CAMs transdifferentiated into CD45-CD90+ fibroblast-like cells that exhibited spindle shapes. Then, cDNA microarray analysis showed that the CD45-CD90+ fibroblast-like cells (macrophage-derived CAFs: MDCAFs) had a fibroblast-specific gene expression signature and produced growth factors for epithelial cell proliferation. Human colon cancer cells transplanted into immunodeficient mice with MDCAFs formed larger tumors than cancer cells alone. Gene ontology analyses showed the involvement of TGFß signaling and cell-matrix adhesion in MDCAFs, and transdifferentiation of CAMs into MDCAFs was canceled by inhibiting TGFß and cell adhesion. Furthermore, the acquired genetic alterations in hematopoietic stem cells (HSCs) were shared in CAMs and MDCAFs. Taken together, CAMs could be a source of CAFs and might originate from HSCs. We propose the transdifferentiation process of CAMs into MDCAFs as a new therapeutic target for fibrosis associated with gastrointestinal cancer.

Treatment Efficacy of PD-1 Inhibitor Therapy in Patients With Recurrent and/or Metastatic Salivary Gland Carcinoma.

BACKGROUND/AIM: The efficacy of programmed cell death 1 (PD-1) inhibitor therapy for patients with recurrent and/or metastatic salivary gland carcinoma (R/M SGC) remains unclear. PATIENTS AND METHODS: We retrospectively analyzed 36 patients with R/M SGC treated with PD-1 inhibitor. The expression of programmed cell death ligand 1 (PD-L1) and mismatch repair (MMR) proteins was also analyzed. RESULTS: The objective response rate (ORR) was 11.1%. The histopathological subtypes of patients who achieved complete response or partial response were salivary duct carcinoma (SDC) in three patients and poorly differentiated carcinoma in one patient, all of whom showed a positive PD-L1 expression. The expression of MMR proteins was not associated with the efficacy of PD-1 inhibitors. CONCLUSION: Although the efficacy of PD-1 inhibitor therapy in R/M SGC is limited, certain patients may respond and achieve long-term disease control. There is a potential therapeutic effect in SDC patients with positive PD-L1 expression.

Amebic liver abscess by Entamoeba histolytica.

Amebic liver abscesses (ALAs) are the most commonly encountered extraintestinal manifestation of human invasive amebiasis, which results from Entamoeba histolytica (E. histolytica) spreading extraintestinally. Amebiasis can be complicated by liver abscess in 9% of cases, and ALAs led to almost 50000 fatalities worldwide in 2010. Although there have been fewer and fewer cases in the past several years, ALAs remain an important public health problem in endemic areas. E. histolytica causes both amebic colitis and liver abscess by breaching the host's innate defenses and invading the intestinal mucosa. Trophozoites often enter the circulatory system, where they are filtered in the liver and produce abscesses, and develop into severe invasive diseases such as ALAs. The clinical presentation can appear to be colitis, including upper-right abdominal pain accompanied by a fever in ALA cases. Proper diagnosis requires nonspecific liver imaging as well as detecting anti-E. histolytica antibodies; however, these antibodies cannot be used to distinguish between a previous infection and an acute infection. Therefore, diagnostics primarily aim to use PCR or enzyme-linked immunosorbent assay to detect E. histolytica. ALAs can be treated medically, and percutaneous catheter drainage is only necessary in approximately 15% of cases. The indicated treatment is to administer an amebicidal drug (such as tinidazole or metronidazole) and paromomycin or other luminal cysticidal agent for clinical disease. Prognosis is good with almost universal recovery. Establishing which diagnostic methods are most efficacious will necessitate further analysis of similar clinical cases.

Diffuse large B cell lymphoma originating from the maxillary sinus with skin metastases: A case report and review of literature.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common type of malignant lymphoma (ML), accounting for 30%-40% of cases of non-Hodgkin's lymphoma (NHL) in adults. Primary paranasal sinus lymphoma is a rare presentation of extranodal NHL that accounts for only 0.17% of all lymphomas. ML from the maxillary sinus (MS) is a particularly rare presentation, and is thus often difficult to diagnose. We have reported the first known case of DLBCL originating from the MS with rapidly occurrent multiple skin metastasis. CASE SUMMARY: An 81-year-old Japanese man visited our hospital due to continuous pain for 12 d in the left maxillary nerve area. His medical history included splenectomy due to a traffic injury, an old right cerebral infarction from when he was 74-years-old, hypertension, and type 2 diabetes mellitus. A plain head computed tomography (CT) scan revealed a 3 cm × 3.1 cm × 3 cm sized left MS. On day 25, left diplopia and ptosis occurred, and a follow-up CT on day 31 revealed the growth of the left MS mass. Based on an MS biopsy on day 50, we established a definitive diagnosis of DLBCL, non-germinal center B-cell-like originating from the left MS. The patient was admitted on day 62 due to rapid deterioration of his condition, and a plain CT scan revealed the further growth of the left MS mass, as well as multiple systemic metastasis, including of the skin. A skin biopsy on day 70 was found to be the same as that of the left MS mass. We notified the patient and his family of the disease, and they opted for palliative care, considering on his condition and age. The patient died on day 80. CONCLUSION: This case suggests the need for careful, detailed examination, and for careful follow-up, when encountering patients presenting with a mass.

LH Induces De Novo Cholesterol Biosynthesis via SREBP Activation in Granulosa Cells During Ovulation in Female Mice.

In the liver, the sterol response element binding protein (SREBP) and the SREBP cleavage-activated protein (SCAP) complex upregulate cholesterol biosynthesis by gene induction of de novo cholesterol synthetic enzymes (Hmgcr, Cyp51, and Dhcr7). Insulin induced gene 1 (INSIG1) negatively regulates cholesterol biosynthesis by the inhibition of de novo cholesterol biosynthetic gene expression. In the ovary, cholesterol is de novo synthesized; however, the roles of SREBP and its regulators (SCAP and INSIG1) are not well understood. In this study, when immature mice were treated with gonadotropins (eCG followed by hCG), eCG induced and hCG maintained the expression of SREBP-1a, -2, and SCAP granulosa cells, whereas INSIG1 expression was dramatically downregulated after hCG injection. Downregulation of INSIG1 led to generate the SREBPs active form and translocate the SREBPs active form to nuclei. Inhibition of generation of the SREBPs active form by fatostatin or Scap siRNA in both in vivo and in vitro significantly decreased the expressions of de novo cholesterol biosynthetic enzymes, cholesterol accumulation, and progesterone (P4) production compared with the control group. Fatostatin treatment inhibited the ovulation and increased the formation of abnormal corpus luteum which trapped the matured oocyte in the corpus luteum; however, the phenomenon was abolished by P4 administration. The results showed that decreasing INSIG1 level after hCG stimulation activated SREBP-induced de novo cholesterol biosynthesis in granulosa cells of preovulatory follicles, which is essential for P4 production and the rupture of matured oocyte during ovulation process.

Impact of Doping a Phytosteryl Sulfate on the Properties of Liposomes Made of Saturated and Unsaturated Phosphatidylcholines.

The size, dispersibility, and fluidity of DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine), POPC (1-palmitoy-2-oleoyl-sn-glycero-3-phosphocholine), and DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine) liposomes doped with ß-sitosteryl sulfate (PSO4) were comparatively studied. In all three types of liposomes, PSO4 reduced sizes and enhanced the negative values of the ζ-potential. However, the effect on sizes quantitatively differed in the three cases in a manner dependent on their phase behaviors. PSO4 rigidified each type of membrane in its liquid crystalline phase and fluidized the gel phase. It enhanced the glucose trapping efficiency (TE) of both DPPC and DOPC liposomes. The TE of DPPC first increased with the increasing concentration of PSO4, then decreased gradually. On the other hand, in the case of DOPC, the TE increased significantly upon addition of PSO4, then remained nearly constant. Though the exact dependence of TE on the PSO4 concentration differed in the two cases, its effect, in each case, was more than the effect of ß-sitosterol (POH). The ability of PSO4 for reducing the size and enhancing dispersibility and TE of liposomes can be useful for preparing cosmetics and pharmaceutical formulations.

Rapid controlled release by photo-irradiation using morphological changes in micelles formed by amphiphilic lophine dimers.

Photo-induced rapid control of molecular assemblies, such as micelles and vesicles, enables effective and on-demand release of drugs or active components, with applications such as drug delivery systems (DDS) and cosmetics. Thus far, no attempts to optimize the responsiveness of photoresponsive molecular assemblies have been published. We previously reported photoresponsive surfactants bearing a lophine dimer moiety that exhibit fast photochromism in confined spaces, such as inside a molecular assembly. However, rapid control of the micelle structures and solubilization capacity have not yet been demonstrated. In the present work, photo-induced morphological changes in micelles were monitored using in-situ small-angle neutron scattering (SANS) and UV/Vis absorption spectroscopy. An amphiphilic lophine dimer (3TEG-LPD) formed elliptical micelles. These were rapidly elongated by ultraviolet light irradiation, which could be reversed by dark treatment, both within 60 s. For a solution of 3TEG-LPD micelles solubilizing calcein as a model drug molecule, fluorescence and SANS measurements indicated rapid release of the incorporated calcein into the bulk solvent under UV irradiation. Building on these results, we investigated rapid controlled release via hierarchical chemical processes: photoisomerization, morphological changes in the micelles, and drug release. This rapid controlled release system allows for effective and on-demand DDS.

Predictive impact of C-reactive protein to albumin ratio for recurrent or metastatic head and neck squamous cell carcinoma receiving nivolumab.

Although the neutrophil to lymphocyte ratio (NLR) was reported to be a predictive biomarker for clinical outcomes in various types of cancer, including recurrent or metastatic head and neck cancer (R/M HNSCC) treated with nivolumab, the usefulness of the pretreatment C-reactive protein/albumin ratio (CAR) as a prognostic marker remains to be clarified. This study aimed to analyze the clinical usability of the CAR in comparison with that of the NLR. 46 R/M HNSCC patients treated with nivolumab were retrospectively analyzed. The optimal cutoff value for the CAR was calculated using receiver operating characteristic curve analysis. The optimal cutoff value for the CAR was set to 0.30. On multivariate analyses, a high CAR was significantly associated with poor overall survival (adjusted HR, 2.19; 95% CI, 1.42-3.47; p < 0.01) and progression-free survival (adjusted HR, 1.98; 95% CI, 1.38-2.80; p < 0.01). The overall response rate and disease control rate for the high CAR patients were lower than for the low CAR patients. The CAR had significantly higher area under the curve values than the NLR at 2 and 4 months. The pretreatment CAR might be an independent marker for prognosis and efficacy in R/M HNSCC patients treated with nivolumab.