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BACKGROUND: Neuronal dysfunction is implicated in the pathophysiology of asthma and functional dyspepsia (FD). However, the relationship between these diseases remains unclear. OBJECTIVE: This study aimed to clarify the clinical implications of comorbid FD in asthma and to explore the unified pathway between asthma and FD by focusing on airway neuronal dysfunction. METHODS: Clinical indices and biomarkers, including capsaicin cough sensitivity (C-CS), were compared between patients with asthma with and without FD. C-CS was determined on the basis of capsaicin concentration that induced at least 2 coughs (C2) or 5 coughs (C5). Additionally, the associations of airway inflammation with airway innervation and gastrointestinal motility were evaluated in mouse models of type 2 airway inflammation. RESULTS: Patients with asthma with FD had worse asthma control and cough severity and lower C2 and C5 thresholds than those without FD. The severity of FD symptoms was negatively correlated with C2 and C5 thresholds. FD and poor asthma control were predictors of heightened C-CS (defined as C5 ≤ 2.44 µmol) in asthma. A mouse model of papain-induced airway inflammation developed airway hyperinnervation and gastrointestinal dysmotility, and both pathologies were ameliorated by an anti-IL-33 antibody. Moreover, papain-induced gastrointestinal dysmotility was mitigated by silencing the airway sensory neurons using QX-314, a sodium channel blocker. Furthermore, sputum IL-33 levels were significantly elevated in patients with asthma with FD or heightened C-CS compared to their counterparts. CONCLUSION: FD is significantly associated with airway neuronal dysfunction in asthma. IL-33-mediated airway neuronal dysfunction may contribute to the interaction between asthma and FD.
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BACKGROUND: Teicoplanin is used to treat serious Gram-positive bacterial infections. However, the optimal trough concentrations for pediatric patients remain unclear owing to the lack of monitoring guidelines. This study aimed to determine the optimal teicoplanin trough concentration for treating Gram-positive bacterial infections in children. METHODS: A systematic review was conducted using 4 databases. Stepwise cutoffs within the range of 10-30 mcg/mL were used for efficacy and safety. Studies were included if they reported treatment success rates and/or all-cause mortality, nephrotoxicity, hepatotoxicity, and thrombocytopenia according to the trough concentration. RESULTS: The meta-analysis included 12 studies involving 830 pediatric patients. Teicoplanin cutoff values of 10, 15, 20, and 30 mcg/mL were reported in 9, 8, 9, and 2 studies, respectively. Trough concentrations <10 mcg/mL significantly reduced the treatment success rate, with an odds ratio of 0.07 and a 95% confidence interval ranging from 0.01 to 0.40. The overall treatment success rate was 50.0% versus 95.7% observed at concentrations ≥10 mcg/mL. However, no significant difference was observed at the 15-, 20-, and 30-mcg/mL cutoffs, when compared with lower concentrations. Trough concentrations <20 mcg/mL were associated with a decreased risk of nephrotoxicity (odds ratio = 0.21; 95% confidence interval, 0.08-0.55). However, hepatotoxicity and thrombocytopenia showed no significant associations with trough concentration ranges between 10 and 30 mcg/mL. CONCLUSIONS: Although further prospective studies are required for validation, the authors' findings suggest that 10- to 20-mcg/mL teicoplanin is the optimal trough concentration for enhanced clinical success and reduced toxicity in pediatric patients.
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INTRODUCTION: This study evaluated the effect of coinfections and/or secondary infections on antibiotic use in patients hospitalized with coronavirus disease 2019 (COVID-19). METHOD: Days of therapy per 100 bed days (DOT) in a COVID-19 ward were compared between 2022 (Omicron period) and 2021 (pre-Omicron period). Antibiotics were categorized as antibiotics predominantly used for community-acquired infections (CAIs) and antibiotics predominantly used for health care-associated infections (HAIs). Bacterial and/or fungal infections which were proved or assumed on admission were defined as coinfections. Secondary infections were defined as infections that occurred following COVID-19. RESULTS: Patients with COVID-19 during the Omicron period were older and had more comorbidities. Coinfections were more common in the Omicron period than in the pre-Omicron period (44.4% [100/225] versus 0.8% [2/257], respectively, p < 0.001), and the mean DOT of antibiotics for CAIs was significantly increased in the Omicron period (from 3.60 to 17.84, p < 0.001). Secondary infection rate tended to be higher in the Omicron period (p = 0.097). Mean DOT of antibiotics for HAIs were appeared to be lower in the COVID-19 ward than in the general ward (pre-Omicron, 3.33 versus 6.37, respectively; Omicron, 3.84 versus 5.22, respectively). No multidrug-resistant gram-negative organisms were isolated in the COVID-19 ward. CONCLUSION: Antibiotic use for CAIs was limited in the pre-Omicron period but increased in the Omicron period because of a high coinfection rate on admission. With the antimicrobial stewardship, excessive use of antibiotics for HAIs was avoided in the COVID-19 ward during both periods.
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Antibacterianos , COVID-19 , Coinfección , Hospitalización , SARS-CoV-2 , Humanos , Coinfección/tratamiento farmacológico , Coinfección/epidemiología , COVID-19/epidemiología , COVID-19/complicaciones , Antibacterianos/uso terapéutico , Masculino , Femenino , Anciano , Persona de Mediana Edad , Hospitalización/estadística & datos numéricos , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/epidemiología , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/epidemiología , Infección Hospitalaria/epidemiología , Infección Hospitalaria/tratamiento farmacológico , Anciano de 80 o más Años , Micosis/epidemiología , Micosis/tratamiento farmacológico , Estudios Retrospectivos , Programas de Optimización del Uso de los AntimicrobianosRESUMEN
PURPOSE: We aimed to evaluate the influence of easing COVID-19 preventive measures following its downgrading to a common infectious disease on COVID-19 occurrence among hospitalized patients. METHODS: Nosocomial occurrence of COVID-19 was compared between periods with national infectious disease category 5 versus the preceding category 2 equivalent. Changes in the revised manual included a shorter duration of work restrictions for infected health care practitioners (HCPs); no work restriction for HCPs exposed to SARS-CoV-2 with a negative test on days 1, 3 and 5; discontinuation of universal pre-admission screening; and pre-emptive isolation of patients without screening. Wearing an N95 mask and face shield was required in procedure/care with moderate-to high-risk contact. RESULTS: Although the mean monthly number of infected HCPs increased from 8.1 to 12.7 in the category 5 period (p = 0.034) and that of pre-admission screening decreased to one-fourth, the COVID-19 incidence in hospitalized patients remained similar between the two study periods (1.60 ± 5.59/month versus 1.40 ± 2.63/month, p = 0.358). Clusters, defined as ≥3 COVID-19 patients on the ward, were experienced twice in the preceding period and only once in the category 5 period. The index cases causing nosocomial SARS-CoV-2 transmission mostly involved rehabilitation therapists in the preceding period; five of six index cases were patients in the category 5 period. Following the expanded indication for N95 masks, neither SARS-CoV-2 transmission to patients nor transmission from infected patients was observed in HCPs for 1 year. CONCLUSION: With sustained, enhanced standard precautions, easing prevention strategies could limit nosocomial SARS-CoV-2 infections.
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Pasteurellosis is a common zoonotic infection that occurs after an animal bite or scratch (B/S). We compared the clinical features of six patients with non-B/S pasteurellosis with those of 14 patients with B/S infections. Pasteurella multocida was identified with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in all six non-B/S infections, whereas 13 of the 14 B/S infections were identified with diagnostic kits. The non-B/S infections were pneumonia (n = 3), skin and soft tissue infections (n = 2), and bacteremia (n = 1). Pneumonia occurred in two patients with underlying pulmonary disease, whereas ventilator-associated pneumonia developed in one patient with cerebral infarction. Pasteurella multocida was isolated from a blood specimen and nasal swab from a patient with liver cirrhosis (Child-Pugh class C) and diabetes. Cellulitis developed in one patient with diabetes and normal-pressure hydrocephalus, who had an open wound following a fall, and in one patient with diabetes and a foot ulcer. Three patients with non-B/S infections had no pet and no episode of recent animal contact. The rate of moderate-to-severe comorbidities was significantly higher in patients with non-B/S infections than in those with B/S infections (100% and 14.3%, respectively, p < 0.001). In conclusion, non-B/S infections can develop in patients with chronic pulmonary disease, invasive mechanical ventilation, or open wounds, or who are immunocompromised, irrespective of obvious animal exposure. In contrast to B/S infections, non-B/S pasteurellosis should be considered opportunistic.
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Mordeduras y Picaduras , Infecciones por Pasteurella , Pasteurella multocida , Humanos , Infecciones por Pasteurella/microbiología , Infecciones por Pasteurella/diagnóstico , Animales , Masculino , Femenino , Pasteurella multocida/aislamiento & purificación , Persona de Mediana Edad , Anciano , Mordeduras y Picaduras/complicaciones , Mordeduras y Picaduras/microbiología , Anciano de 80 o más Años , Adulto , Bacteriemia/microbiología , Bacteriemia/diagnósticoRESUMEN
BACKGROUND: Acute kidney injury (AKI) and hypokalaemia are common adverse events after treatment with liposomal amphotericin B (L-AMB). OBJECTIVES: Because excess potassium (K) leakage occurs during renal tubular injury caused by L-AMB, measuring the decrease in rate of serum K concentration might be more useful to assess the renal impact of L-AMB than hypokalaemia identified from a one-point measurement. The effects of a decrease in K concentration and duration of hypokalaemia on AKI were investigated. METHODS: A ≥ 10% decrease in K concentration from the reference concentration within a 7-day timeframe was evaluated. The hypokalaemia index, which combines the duration of K concentration lower than the reference and a marked low K concentration, was calculated from the area over the concentration curve. RESULTS: Eighty-six patients were included in the study. The incidences of AKI and decrease in K concentration were 36.0% and 63.9%, respectively. Of patients who developed both adverse events, a decrease in K concentration occurred first in 22 of 26 patients, followed by AKI 7 days later. Hypokalaemia did not increase AKI risk whereas a decrease in K concentration was an independent risk factor for AKI. The hypokalaemia index in patients with AKI was significantly higher than those without AKI (5.35 vs. 2.50 points, p = 0.002), and ≥3.45 points was a significant predictor for AKI. CONCLUSION: A ≥ 10% decrease in the K concentration was a significant factor for AKI in patients receiving L-AMB therapy. In such patients, dose reduction or alternative antifungals could be considered based on the hypokalaemia index.
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Lesión Renal Aguda , Anfotericina B , Antifúngicos , Hipopotasemia , Potasio , Humanos , Hipopotasemia/inducido químicamente , Hipopotasemia/sangre , Anfotericina B/efectos adversos , Anfotericina B/administración & dosificación , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/sangre , Masculino , Potasio/sangre , Femenino , Persona de Mediana Edad , Anciano , Antifúngicos/efectos adversos , Antifúngicos/administración & dosificación , Adulto , Estudios Retrospectivos , Factores de Riesgo , Incidencia , Anciano de 80 o más AñosRESUMEN
OBJECTIVE: We developed fiducial imaging-guidance markers for the prostate with less imaging artifacts than currently commercially available markers. The aim of this study was to evaluate the imaging artifacts and potential usefulness and safety of these novel fiducial imaging markers in preclinical experiments. METHODS: We selected specific metal materials and a shape that can minimize artifacts in line with a license we obtained for a metal with a gold-platinum (Au-Pt) alloy composition that maximized artifact-free MRI images. Both phantom and canine prostate tests were conducted in order to evaluate the imaging artifacts for three imaging modalities, MRI, CT and ultrasound, and the risk of migration of the markers from the site of insertion to elsewhere, as well as crushing. RESULTS: The newly developed Au-Pt material had less imaging artifacts in the MRI, CT and ultrasound imaging modalities in comparison with current commercially available fiducial markers made from gold materials only. The Au-Pt markers had sufficient strength and durability and were considered to be potentially clinically useful and safe markers. CONCLUSION: The developed Au-Pt markers could be potential tools for accurate lesion-targeted, organ-preserving therapies such as lesion-targeted focal therapy and active surveillance in addition to conventional radiation therapies.
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Marcadores Fiduciales , Oro , Imagen por Resonancia Magnética , Fantasmas de Imagen , Neoplasias de la Próstata , Masculino , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/terapia , Perros , Animales , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Rayos X , Artefactos , Próstata/diagnóstico por imagen , Próstata/patología , Platino (Metal) , Ultrasonografía/métodos , Humanos , Tratamientos Conservadores del Órgano/métodosRESUMEN
An 87-year-old man experiencing lower abdominal discomfort resulting from the ingestion of a fish bone underwent conservative management involving endoscopic extraction of the fish bone lodged in the sigmoid colon. Most patients with lower gastrointestinal tract perforations typically develop peritonitis or abscesses, necessitating surgical intervention. Notably, endoscopic management of lower gastrointestinal tract perforations is infrequently employed. Patients presenting with localized abdominal symptoms along with a stable overall health condition may benefit from conservative therapeutic approaches that utilize endoscopic methods. Notably, the transition from endoscopic procedures for foreign body removal to surgical intervention requires close collaboration with a surgeon and must be executed judiciously.
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Abdominal pseudohernia is a condition characterized by the protrusion of abdominal viscera through a weakened area of the abdominal wall without a hernia sac. Various causes, including spinal disorders and trauma, can lead to this condition; however, the most common cause is reported to be herpes zoster. We present a rare case of spontaneous resolution of abdominal pseudohernia following lung cancer surgery. A 71-year-old male presented with left upper abdominal bulging and pain. A CT scan performed at the time incidentally revealed a nodular lesion in the right lower lobe, suspicious for lung cancer. Single-port thoracoscopic surgery was performed, and the final diagnosis was right lower lobe lung squamous cell carcinoma. Following the lung cancer surgery, the left upper abdominal bulging spontaneously resolved within one week. In this case, we hypothesize that the immune dysregulation caused by lung cancer increased the activity of the herpes zoster virus, leading to the development of pseudohernia. The spontaneous resolution of the pseudohernia is thought to be due to the improvement of immune dysregulation after surgery.
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The misdiagnosis of intestinal tuberculosis (ITB), such as Crohn's disease (CD), and subsequent treatment with immunosuppressive therapies can lead to severe outcomes. However, the differential diagnosis between these two conditions can be challenging. We herein report a patient from Myanmar who was initially diagnosed with CD due to the presence of non-caseating granulomas. The patient's symptoms were aggravated with steroid treatment, eventually leading to a diagnosis of ITB. In the international medical community, we encounter patients from countries, such as Myanmar, where tuberculosis is endemic. Therefore, it is necessary to understand the epidemiological background of each country to accurately distinguish between CD and ITB.
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A 55-year-old woman presented to her primary care physician with facial and lower leg edema. After being referred to our hospital because of hypothyroidism and hypokalemia on blood tests, she also had elevated adrenocorticotropic hormone (ACTH) and cortisol levels, but a dexamethasone suppression test showed no cortisol suppression. Ectopic ACTH syndrome due to pancreatic neuroendocrine carcinoma (PNEC) was suspected. endoscopic ultrasound-guided fine-needle aspiration was performed, and a histopathological examination of the obtained specimen revealed multiple liver metastases of the PNEC. Imaging after etoposide and cisplatin therapy showed cystic changes in the primary lesions and shrinkage of the liver metastases, and the ACTH levels were within the normal range.
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Assessment of the immune response to influenza vaccines should include an assessment of both humoral and cell-mediated immunity. However, there is a lack of consensus regarding the timing of immunological assessment of humoral and cell-mediated immunity after vaccination. Therefore, we investigated the timing of immunological assessments after vaccination using markers of humoral and cell-mediated immunity. In the 2018/2019 influenza season, blood was collected from 29 healthy adults before and after vaccination with a quadrivalent inactivated influenza vaccine, and we performed serial measurements of humoral immunity (hemagglutination inhibition [HAI] and neutralizing antibody [NT]) and cell-mediated immunity (interferon-gamma [IFN-γ]). The HAI and NT titers before and after vaccination were strongly correlated, but no correlation was observed between the markers of cell-mediated and humoral immunity. The geometric mean titer and geometric mean concentration of humoral and cellular immune markers increased within 2 weeks after vaccination and had already declined by 8 weeks. This study suggests that the optimal time to assess the immune response is 2 weeks after vaccination. Appropriately timed immunological assessments can help ensure that vaccination is effective.
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An Arabidopsis sterol mutant, smt2 smt3, defective in sterolmethyltransferase2 (SMT2), exhibits severe growth abnormalities. The loss of C-24 ethyl sterols, maintaining the biosynthesis of C-24 methyl sterols and brassinosteroids, suggests specific roles of C-24 ethyl sterols. We characterized the subcellular localizations of fluorescent protein-fused sterol biosynthetic enzymes, such as SMT2-GFP, and found these enzymes in the endoplasmic reticulum during interphase and identified their movement to the division plane during cytokinesis. The mobilization of endoplasmic reticulum-localized SMT2-GFP was independent of the polarized transport of cytokinetic vesicles to the division plane. In smt2 smt3, SMT2-GFP moved to the abnormal division plane, and unclear cell plate ends were surrounded by hazy structures from SMT2-GFP fluorescent signals and unincorporated cellulose debris. Unusual cortical microtubule organization and impaired cytoskeletal function accompanied the failure to determine the cortical division site and division plane formation. These results indicated that both endoplasmic reticulum membrane remodeling and cytokinetic vesicle transport during cytokinesis were impaired, resulting in the defects of cell wall generation. The cell wall integrity was compromised in the daughter cells, preventing the correct determination of the subsequent cell division site. We discuss the possible roles of C-24 ethyl sterols in the interaction between the cytoskeletal network and the plasma membrane.
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Proteínas de Arabidopsis , Arabidopsis , Citocinesis , Retículo Endoplásmico , Metiltransferasas , Esteroles , Arabidopsis/genética , Arabidopsis/metabolismo , Metiltransferasas/metabolismo , Metiltransferasas/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Esteroles/metabolismo , Citocinesis/genética , Retículo Endoplásmico/metabolismo , División Celular/genética , Mutación , Microtúbulos/metabolismo , Pared Celular/metabolismoRESUMEN
The objective of this study is to compare the efficacy of apalutamide and bicalutamide in combination with androgen deprivation therapy in patients with metastatic hormone-sensitive prostate cancer (mHSPC). We retrospectively collected the data of about 330 patients with metastatic hormone-sensitive prostate cancer at our hospital and affiliated hospitals between December 2013 and August 2023. Sixty-one patients were administered apalutamide (240 mg/day) with androgen deprivation therapy (group A), and 269 patients were administered bicalutamide (80 mg/day) with androgen deprivation therapy (group B). Propensity score matching was used to adjust for clinical background factors between the two groups. PSA progression-free survival and overall survival were significantly longer in group A than in group B among the matched patients. Apalutamide therapy was a significant independent factor for OS in matched patients. The second progression-free survival of group A was significantly longer than that of group B in matched patients. Patients treated with apalutamide achieved ≥ 90% PSA decline from baseline faster and in larger numbers than those with bicalutamide. Apalutamide combined with ADT may be superior to bicalutamide alone in terms of OS and PSA-PFS in patients with mHSPC.
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Antagonistas de Andrógenos , Neoplasias de la Próstata , Masculino , Humanos , Antagonistas de Andrógenos/uso terapéutico , Andrógenos , Antígeno Prostático Específico , Neoplasias de la Próstata/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
A 71-year-old woman was found to have submucosal tumor-like lesion on colonoscopy (CS) before gastric surgery, and computed tomography (CT) showed a 12-mm structure at the base of the appendix. The lesion could not be clearly detected on CT nine months later, but it had enlarged again on CT one year later; therefore, CS and endoscopic ultrasound (EUS) were performed. The lesion was determined to be cystic with viscous contents, and laparoscopic appendicectomy was performed. This is the first report of low-grade appendiceal mucinous neoplasm (LAMN) diagnosed by a histopathologic examination of a resected specimen showing shrinkage and re-expansion of the appendix.
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Germ cells preferentially induce apoptosis in response to DNA damage to avoid genomic mutations. Apoptosis of germ cells is closely related to cancer development and chemotherapy resistance; however, its regulatory mechanism is unclear. Here, we suggest that testis-specific lncRNA LINC03074 is involved in male germ cell apoptosis by regulating the expression of the proto-oncogene MDM2. LINC03074 is highly expressed in the sperm of healthy adult testes and cancer cells of testes with testicular germ cell tumors (TGCTs). LINC03074 binds to MDM2 mRNA via an Alu element, thereby reducing MDM2 protein levels. LINC03074 stimulates STAU1-mediated nuclear export of MDM2 mRNA by increasing STAU1 binding to MDM2 mRNA in the cell nucleus, thereby promoting PKR-mediated translational repression in the cytoplasm. The induction of apoptosis in TGCT cells and their responsiveness to the anticancer drug cisplatin is enhanced by LINC03074. Notably, LINC03074 increased E2F1 expression without increasing p53, the primary target of MDM2, and upregulated the apoptotic gene p73, the target gene of E2F1. LINC03074-mediated regulation of apoptosis contributes to the responsiveness of TGCTs to anticancer drug-induced DNA damage.
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Gametogenesis, which is essential to the sexual reproductive system, has drastically changed during plant evolution. Bryophytes, lycophytes and ferns develop reproductive organs called gametangia-antheridia and archegonia for sperm and egg production, respectively. However, the molecular mechanism of early gametangium development remains unclear. Here we identified a 'non-canonical' type of BZR/BES transcription factor, MpBZR3, as a regulator of gametangium development in a model bryophyte, Marchantia polymorpha. Interestingly, overexpression of MpBZR3 induced ectopic gametangia. Genetic analysis revealed that MpBZR3 promotes the early phase of antheridium development in male plants. By contrast, MpBZR3 is required for the late phase of archegonium development in female plants. We demonstrate that MpBZR3 is necessary for the successful development of both antheridia and archegonia but functions in a different manner between the two sexes. Together, the functional specialization of this 'non-canonical' type of BZR/BES member may have contributed to the evolution of reproductive systems.