Time definition of reintubation most relevant to patient outcomes in critically ill patients: a multicenter cohort study

Background: Reintubation is a common complication in critically ill patients requiring mechanical ventilation. Although reintubation has been demonstrated to be associated with patient outcomes, its time definition varies widely among guidelines and in the literature. This study aimed to determine the association between reintubation and patient outcomes as well as the consequences of the time elapsed between extubation and reintubation on patient outcomes. Methods: This was a multicenter retrospective cohort study of critically ill patients conducted between April 2015 and March 2021. Adult patients who underwent mechanical ventilation and extubation in intensive care units (ICUs) were investigated utilizing the Japanese Intensive Care PAtient Database. The primary and secondary outcomes were in-hospital and ICU mortality. The association between reintubation and clinical outcomes was studied using Cox proportional hazards analysis. Among the patients who underwent reintubation, a Cox proportional hazard analysis was conducted to evaluate patient outcomes according to the number of days from extubation to reintubation. Results: Overall, 184,705 patients in 75 ICUs were screened, and 1849 patients underwent reintubation among 48,082 extubated patients. After adjustment for potential confounders, multivariable analysis revealed a significant association between reintubation and increased in-hospital and ICU mortality (adjusted hazard ratio [HR] 1.520, 95% confidence interval [CI] 1.359–1.700, and adjusted HR 1.325, 95% CI 1.076–1.633, respectively). Among the reintubated patients, 1037 (56.1%) were reintubated within 24 h after extubation, 418 (22.6%) at 24–48 h, 198 (10.7%) at 48–72 h, 111 (6.0%) at 72–96 h, and 85 (4.6%) at 96–120 h. Multivariable Cox proportional hazard analysis showed that in-hospital and ICU mortality was highest in patients reintubated at 72–96 h (adjusted HR 1.528, 95% CI 1.062–2.197, and adjusted HR 1.334, 95% CI 0.756–2.352, respectively; referenced to reintubation within 24 h). Conclusions: Reintubation was associated with a significant increase in in-hospital and ICU mortality. The highest mortality rates were observed in patients who were reintubated between 72 and 96 h after extubation. Further studies are warranted for the optimal observation of extubated patients in clinical practice and to strengthen the evidence for mechanical ventilation.Tanaka A., Shimomura Y., Uchiyama A., et al. Time definition of reintubation most relevant to patient outcomes in critically ill patients: a multicenter cohort study. Critical Care 27, 378 (2023); https://doi.org/10.1186/s13054-023-04668-3

Retroperitoneal abscess complicated with necrotizing fasciitis of the thigh in a patient with sigmoid colon cancer

<p>Abstract</p> <p>Background</p> <p>Necrotizing fasciitis of the thigh due to the colon cancer, especially during chemotherepy, has not been previously reported.</p> <p>Case presentation</p> <p>A 67-year-old man admitted to the hospital was diagnosed with sigmoid colon cancer that had spread to the left psoas muscle. Multiple hepatic metastases were also found, and combination chemotherapy with irinotecan and S-1 was administered. Four months after the initiation of chemotherapy, the patient developed gait disturbance and high fever and was therefore admitted to the emergency department of our hospital. Blood examination revealed generalized inflammation with a high C-reactive protein level. Computed tomography of the abdomen and pelvis showed gas and fluid collection in the retroperitoneum adjacent to the sigmoid colon cancer. The abscess was locally drained under computed tomographic guidance; however, the infection continued to spread and necrotizing fasciitis developed. Consequently, emergent debridement was performed. The patient recovered well, and the primary tumor was resected after remission of the local inflammation.</p> <p>Conclusion</p> <p>Necrotizing fasciitis of the thigh due to the spread of sigmoid colon cancer is unusual, but this fatal complication should be considered during chemotherapy for patients with unresectable colorectal cancer.</p

Crystal Structures of the Quinone Oxidoreductase from Thermus thermophilus HB8 and Its Complex with NADPH: Implication for NADPH and Substrate Recognition

The crystal structures of the ζ-crystalline-like soluble quinone oxidoreductase from Thermus thermophilus HB8 (QOR(Tt)) and of its complex with NADPH have been determined at 2.3- and 2.8-Å resolutions, respectively. QOR(Tt) is composed of two domains, and its overall fold is similar to the folds of Escherichia coli quinone oxidoreductase (QOR(Ec)) and horse liver alcohol dehydrogenase. QOR(Tt) forms a homodimer in the crystal by interaction of the βF-strands in domain II, forming a large β-sheet that crosses the dimer interface. High thermostability of QOR(Tt) was evidenced by circular dichroic measurement. NADPH is located between the two domains in the QOR(Tt)-NADPH complex. The disordered segment involved in the coenzyme binding of apo-QOR(Tt) becomes ordered upon NADPH binding. The segment covers an NADPH-binding cleft and may serve as a lid. The 2′-phosphate group of the adenine of NADPH is surrounded by polar and positively charged residues in QOR(Tt), suggesting that QOR(Tt) binds NADPH more readily than NADH. The putative substrate-binding site of QOR(Tt), unlike that of QOR(Ec), is largely blocked by nearby residues, permitting access only to small substrates. This may explain why QOR(Tt) has weak p-benzoquinone reduction activity and is inactive with such large substrates of QOR(Ec) as 5-hydroxy-1,4-naphthoquinone and phenanthraquinone

The Asymmetric Trimeric Architecture of [2Fe–2S] IscU: Implications for Its Scaffolding during Iron–Sulfur Cluster Biosynthesis

IscU is a key component of the ISC machinery and is involved in the biogenesis of iron-sulfur (Fe-S) proteins. IscU serves as a scaffold for assembly of a nascent Fe-S cluster prior to its delivery to an apo protein. Here, we report the first crystal structure of IscU with a bound [2Fe-2S] cluster from the hyperthermophilic bacterium Aquifex aeolicus, determined at a resolution of 2.3 angstrom, using multiwavelength anomalous diffraction of the cluster. The holo IscU formed a novel asymmetric trimer that harbored only one [2Fe-2S] cluster. One iron atom of the cluster was coordinated by the S-gamma atom of Cys36 and the N-epsilon atom of Hs106, and the other was coordinated by the S-gamma atoms of Cys63 and Cys107 on the surface of just one of the protomers. However, the cluster was buried inside the trimer between the neighboring protomers. The three protomers were conformationally distinct from one another and associated around a noncrystallographic pseudo-3-fold axis. The three flexible loop regions carrying the ligand-binding residues (Cys36, Cys63,His106 and Cys107) and the N-terminal alpha 1 helices were positioned at the interfaces and underwent substantial conformational rearrangement, which stabilized the association of the asymmetric trimer. This unique trimeric A. aeolicus holo-IscU architecture was clearly distinct from other known monomeric apo-IscU/SufU structures, indicating that asymmetric trimer organization, as well as its association/dissociation, would be involved in the scaffolding function of IscU. (C) 2008 Elsevier Ltd. All rights reserved

Clinical features and outcomes of duodenal‐type follicular lymphoma: A single‐center retrospective study

Abstract Duodenal‐type follicular lymphoma (FL) is a rare and newly recognized disease. Few data are available on the outcomes and treatment strategies for patients with duodenal‐type FL. We aimed to investigate the clinical features and outcomes of duodenal‐type FL. We defined duodenal‐type FL as involvement of the duodenum, without nodal or extranodal lesions other than intestinal lesions, pathologically diagnosed as FL. We reviewed 26 patients with duodenal‐type FL between January 2011 and December 2020 at Kobe City Hospital Organization, Kobe City Medical Center General Hospital. In particular, patients were selected for the watch and wait (WW) strategy and followed up with regular esophagogastroduodenoscopy about once a year at our institution. The patient characteristics were as follows: median age 63.5 years (range: 42–78), sex (male, 15; female, 11), stage (I, 26), and grade (I, 26). Regarding treatment strategies, 23 patients were selected for the WW strategy, and three patients received initial rituximab therapy. The median follow‐up period was 65.5 months (range: 0.2–109). Five‐year progression‐free survival and 5‐year overall survival rates were 86.3% and 100%, respectively. Among the 23 patients selected for the WW strategy, six had spontaneous complete regression, and 14 had stable disease, and three had progressive disease, including one with histologic transformation. The WW strategy for patients with duodenal‐type FL could be an appropriate and safe treatment option. However, in several cases, disease progression was documented, and regular follow‐up is important

Encapsulating peritoneal sclerosis in a patient after allogeneic hematopoietic stem cell transplantation: a case report

Abstract Background Encapsulating peritoneal sclerosis (EPS) is a chronic clinical syndrome of acute or subacute gastrointestinal obstruction seen mainly in patients undergoing peritoneal dialysis. Although there are a few reports on EPS developing in non-peritoneal dialysis patients, it has not been reported in patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT). Here, we report a case of EPS after a second HSCT. Case presentation A 46-year-old man with myelodysplastic syndrome showed relapse after HSCT and received a second HSCT. The patient was diagnosed with chronic graft-versus-host disease (cGVHD)-associated serositis because of persistent ascites. His ascites improved gradually and disappeared without immunosuppressive therapy. He presented with nausea, weight loss, and constipation 1 year after improvement of ascites. Computed tomography revealed no organic obstruction, but did reveal dilated, thickened, and adhered small bowel loops with a mass-like appearance. He was diagnosed with EPS on the basis of clinical symptoms and image findings. He received corticosteroid therapy (20 mg/body) without any improvement in symptoms. He developed recurrence of myelodysplastic syndrome at 1 month after initiation of corticosteroid therapy. This progressed into acute myeloid leukaemia after 3 months. He died 31 months after the second HSCT. At autopsy, the small and large intestines had formed extensive adhesions and showed signs of progressive fibrosis with peritoneal sclerosis, fibroblast swelling, fibrin deposition, and inflammatory cell infiltration, which confirmed the diagnosis of EPS. Conclusion This case suggests that EPS may complicate patients with cGVHD-associated serositis. Although the mechanism of EPS development is not clear, clinicians should be aware of this eventuality

Direct infiltration of clonal plasma cells causes renal insufficiency in patients with monoclonal gammopathy of undetermined significance

Abstract Monoclonal gammopathy of undetermined significance (MGUS) is a benign but precancerous condition that can progress to multiple myeloma. Patients with MGUS are typically monitored closely for signs of disease progression, but in some cases, they may also develop renal insufficiency, a condition known as monoclonal gammopathy of renal significance (MGRS). In MGRS, M‐protein secreted by a nonmalignant or premalignant cell clone triggers renal damage by definition. Herein, we report a case of a 66‐year‐old Asian male with MGUS complicated by renal insufficiency. A kidney biopsy showed no evidence of renal injury mediated by M‐protein; instead, the direct infiltration of clonal cells into renal tissues was observed. Although five similar cases have been previously reported, our case is unique in that the involvement of clonal cells was directly confirmed by fluorescence in situ hybridization. Our findings suggest the need to consider a novel disease concept, as this phenomenon appears to be reproduced