Franseen needle in endobronchial ultrasound-guided transbronchial needle aspiration: a phase II prospective study.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been used to diagnose and stage lung cancer. Acquire™ Pulmonary and Expect™ Pulmonary dedicated EBUS-TBNA needles were introduced as the Franseen and Lancet needles, respectively. It is still unclear whether the Franseen or Lancet needles yield a higher quality specimen especially focusing on next-generation sequencing-based molecular testing. METHODS: A single-center, prospective study performed at the Chiba University Hospital randomly assigned patients to two groups: Group A, wherein the first and second EBUS-TBNA were performed using Lancet and Franseen needles, respectively, and Group B, wherein the first and second EBUS-TBNA were performed using Franseen and Lancet needles, respectively. Each specimen was compared and analyzed pathologically. The primary outcome was the histological tissue area except blood clot and the cellularity of each sample. We also examined the success rate of molecular testing. RESULTS: Twelve patients who underwent EBUS-TBNA between November 2022 and February 2023 were enrolled in this study. The tissue area of the specimens obtained by the Franseen and Lancet needles was 13.3 ± 6.4 mm2 and 10.6 ± 6.3 mm2, respectively (P = .355). The tumor cellularity in the specimens obtained using the Franseen and Lancet needles was 54.0 ± 30.3 and 46.2 ± 36.3%, respectively (P = .608). The success rate of molecular testing using the single-pass sample by Franseen needle was 85.7 and 57.1% by Lancet needle. No serious complications were reported. CONCLUSIONS: The Franseen needle tended to show a greater amount of specimen with higher tumor cellularity than the Lancet needle which may contribute higher success rate of molecular testing. Further studies must be conducted to validate the results of this study. KEY FINDINGS: What is known and what is new?  What is the implication, and what should change now?

Carcinogenesis and epidemiology of cervical cancer: The hallmark of human papillomavirus-associated cancer.

Cervical cancer affects women worldwide and is the most common human papillomavirus (HPV)-associated cancer. Carcinogenesis caused by HPV results in specific cancer behavior because of the underlying viral infection. The mechanism and timing of the transformation from viral infection to cancer cells have been elucidated in detail. Treatments for this cancer are based on its characteristics and are being implemented. Moreover, HPV infection is widespread worldwide and is transmitted through sexual activity. Although the HPV vaccination is the most effective strategy of preventing cervical cancer, it is not feasible to vaccinate the entire human population especially in low- and middle-income countries. In order to consider the next step for HPV vaccination, we need to understand the characteristics of HPV carcinogenesis and cervical cancer. Additionally, treatment aimed at preservation of reproductive function in patients with cervical cancer is often required, as the cervix is a reproductive organ and because the disease is more prevalent in the adolescent and young adult generation. Thus, there are still many challenges in the diagnosis, treatment, and prevention of cervical cancer.

Association of frequent hypermethylation with high grade histological subtype in lung adenocarcinoma.

Lung adenocarcinoma is classified morphologically into five histological subtypes according to the WHO classification. While each histological subtype correlates with a distinct prognosis, the molecular basis has not been fully elucidated. Here we conducted DNA methylation analysis of 30 lung adenocarcinoma cases annotated with the predominant histological subtypes and three normal lung cases using the Infinium BeadChip. Unsupervised hierarchical clustering analysis revealed three subgroups with different methylation levels: high-, intermediate-, and low-methylation epigenotypes (HME, IME, and LME). Micropapillary pattern (MPP)-predominant cases and those with MPP components were significantly enriched in HME (p = 0.02 and p = 0.03, respectively). HME cases showed a significantly poor prognosis for recurrence-free survival (p < 0.001) and overall survival (p = 0.006). We identified 365 HME marker genes specifically hypermethylated in HME cases with enrichment of "cell morphogenesis" related genes; 305 IME marker genes hypermethylated in HME and IME, but not in LME, with enrichment "embryonic organ morphogenesis"-related genes; 257 Common marker genes hypermethylated commonly in all cancer cases, with enrichment of "regionalization"-related genes. We extracted surrogate markers for each epigenotype and designed pyrosequencing primers for five HME markers (TCERG1L, CXCL12, FAM181B, HOXA11, GAD2), three IME markers (TBX18, ZNF154, NWD2) and three Common markers (SCT, GJD2, BARHL2). DNA methylation profiling using Infinium data was validated by pyrosequencing, and HME cases defined by pyrosequencing results also showed the worse recurrence-free survival. In conclusion, lung adenocarcinomas are stratified into subtypes with distinct DNA methylation levels, and the high-methylation subtype correlated with MPP-predominant cases and those with MPP components and showed a poor prognosis.

M2 tumor-associated macrophages resist to oxidative stress through heme oxygenase-1 in the colorectal cancer tumor microenvironment.

M2 tumor-associated macrophages (M2-TAMs) promote cancer cell proliferation and metastasis in the TME. Our study aimed to elucidate the mechanism of increased frequency of M2-TAMs infiltration in the colorectal cancer (CRC)-TME, focusing on the resistance to oxidative stress through nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. In this study, we evaluated the correlation between M2-TAM signature and mRNA expression of antioxidant related genes using public datasets, and the expression level of antioxidants in M2-TAMs by flow cytometry and the prevalence of M2-TAMs expressing antioxidants by immunofluorescence staining using surgically resected specimens of CRC (n = 34). Moreover, we generated M0 and M2 macrophages from peripheral blood monocytes and evaluated their resistance to oxidative stress using the in vitro viability assay. Analysis of GSE33113, GSE39582, and The Cancer Genome Atlas (TCGA) datasets indicated that mRNA expression of HMOX1 (heme oxygenase-1 (HO-1)) was significantly positively correlated with M2-TAM signature (r = 0.5283, r = 0.5826, r = 0.5833, respectively). The expression level of both Nrf2 and HO-1 significantly increased in M2-TAMs compared to M1- and M1/M2-TAMs in the tumor margin, and the number of Nrf2+ or HO-1+M2-TAMs in the tumor stroma significantly increased more than those in the normal mucosa stroma. Finally, generated M2 macrophages expressing HO-1 significantly resisted to oxidative stress induced by H2O2 in comparison with generated M0 macrophages. Taken together, our results suggested that an increased frequency of M2-TAMs infiltration in the CRC-TME is related to Nrf2-HO-1 axis mediated resistance to oxidative stress.

siRNA potency enhancement via chemical modifications of nucleotide bases at the 5'-end of the siRNA guide strand.

Small interfering RNAs (siRNAs) can be utilized not only as functional biological research tools but also as therapeutic agents. For the clinical use of siRNA as drugs, various chemical modifications have been used to improve the activity of siRNA drugs, and further chemical modifications are expected to improve the utility of siRNA therapeutics. As the 5' nucleobase of the guide strand affects the interaction between an siRNA and AGO2 and target cleavage activity, structural optimization of this specific position may be a useful strategy for improving siRNA activity. Here, using the in silico model of the complex between human AGO2 MID domain and nucleoside monophosphates, we screened and synthesized an original adenine-derived analog, 6-(3-(2-carboxyethyl)phenyl)purine (6-mCEPh-purine), that fits better than the natural nucleotide bases into the MID domain of AGO2. Introduction of the 6-mCEPh-purine analog at the 5'-end of the siRNA guide strand significantly enhanced target knockdown activity in both cultured cell lines and in vivo animal models. Our findings can help expand strategies for rationally optimizing siRNA activity via chemical modifications of nucleotide bases.

Fatty acid metabolism in T-cell function and differentiation.

Immunometabolism has recently emerged as a field of study examining the intersection between immunology and metabolism. Studies in this area have yielded new findings on the roles of a diverse range of metabolic pathways and metabolites, which have been found to control many aspects of T-cell biology, including cell differentiation, function and fate. A particularly important finding has been the discovery that to meet the energy requirements associated with their proliferation, activation and specific functions, T cells switch their metabolic signatures during differentiation. For example, whereas the induction of de novo fatty acid biosynthesis and fatty acid uptake programs are required for antigen-stimulation-induced proliferation and differentiation of effector T cells, fatty acid catabolism via ß-oxidation is essential for the generation of memory T cells and the differentiation of regulatory T cells. In this review, we discuss recent advances in our understanding of the metabolism in different stages of T cells and how fatty acid metabolism in these cells controls their specific functions.

Escherichia coli-derived outer-membrane vesicles induce immune activation and progression of cirrhosis in mice and humans.

BACKGROUND AND AIMS: Decompensated cirrhosis with fibrosis progression causes portal hypertension followed by an oedematous intestinal tract. These conditions weaken the barrier function against bacteria in the intestinal tract, a condition called leaky gut, resulting in invasion by bacteria and bacterial components. Here, we investigated the role of outer-membrane vesicles (OMVs) of Escherichia coli, which is the representative pathogenic gut-derived bacteria in patients with cirrhosis in the pathogenesis of cirrhosis. METHODS: We investigated the involvement of OMVs in humans using human serum and ascites samples and also investigated the involvement of OMVs from E. coli in mice using mouse liver-derived cells and a mouse cirrhosis model. RESULTS: In vitro, OMVs induced inflammatory responses to macrophages and neutrophils, including the upregulation of C-type lectin domain family 4 member E (Clec4e), and induced the suppression of albumin production in hepatocytes but had a relatively little direct effect on hepatic stellate cells. In a mouse cirrhosis model, administration of OMVs led to increased liver inflammation, especially affecting the activation of macrophages, worsening fibrosis and decreasing albumin production. Albumin administration weakened these inflammatory changes. In addition, multiple antibodies against bacterial components were increased with a progressing Child-Pugh grade, and OMVs were detected in ascites of patients with decompensated cirrhosis. CONCLUSIONS: In conclusion, OMVs induce inflammation, fibrosis and suppression of albumin production, affecting the pathogenesis of cirrhosis. We believe that our study paves the way for the future prevention and treatment of cirrhosis.

Skin-to-Renal Pelvis Distance Predicts Costovertebral Angle Tenderness in Adult Patients with Acute Focal Bacterial Nephritis.

OBJECTIVES: The aim of this study was to examine whether the distance between the skin and the renal pelvis affects the detection of costovertebral angle (CVA) tenderness in patients with acute focal bacterial nephritis (AFBN). METHODS: We retrospectively reviewed the charts of our patients between April 2013 and June 2019 who were diagnosed as having AFBN. Diagnosis was based on ultrasound or computed tomography with contrast, revealing at least one wedge-shaped area of decreased vascularity and confirmation of fever not attributable to another condition. RESULTS: We extracted 23 cases, all Japanese (mean age 60.0 years old [range 45-81 years], 7 males, 16 females). CVA tenderness was present in 8 of these 23 patients. Receiver operating characteristic curves were drawn to evaluate the ability to differentiate skin-to-renal pelvis distance (SPD), body mass index, and age. Only SPD was a useful predictor of CVA tenderness, and 66 mm was determined as the optimal cutoff point (area under the receiver operating characteristic curve 0.858, 95% confidence interval 0.70-1.00). Logistic regression analysis was performed with CVA tenderness as a dependent variable, and SPD, body mass index, and age as explanatory variables. SPD was an independent predictive variable of CVA tenderness (P = 0.038, odds ratio 0.76, 95% confidence interval 0.590-0.986). CONCLUSIONS: CVA tenderness showed low yield in the diagnosis of AFBN in patients with longer SPD. Its use for diagnosis in obese patients may therefore be limited.

Hemophagocytic syndrome in a patient with long-term stable pulmonary sarcoidosis with progressive spleen and bone marrow lesion.

An 83-year-old woman with asymptomatic pulmonary sarcoidosis presented to our hospital with fever and malaise for three months. Abdominal CT showed splenomegaly, and bone marrow examination revealed non-caseating granulomas. Pancytopenia was diagnosed due to bone marrow and splenic lesions of sarcoidosis. Steroid pulses were administered, but the patient died without response to treatment. Pathological autopsy results showed non-caseating granulomas and hemophagocytosis in the spleen and bone marrow. This suggested hemophagocytic syndrome, which was not suspected before death, in addition to sarcoidosis. In patients with splenomegaly and pancytopenia with history of pulmonary sarcoidosis, hemophagocytic syndrome should be considered in differential diagnosis.

[Robot-assisted Minimally Invasive Surgery for Mediastinal Tumors].

The subxiphoid approach in thymectomy provides better visibility around the left brachiocephalic vein than the lateral thoracic approach. Robot-assisted thoracoscopic surgery is easier to parform than video- assisted thoracoscopic surgery for surgery of the upper mediastinum, because the forceps can be moved with many joints. Robot-assisted thymectomy using the subxiphoid approach may be less traumatic and less invasive than median sternotomy. We must continue to devise surgical procedures to make oncologically curative surgery more minimally invasive.

[Considerations for Perioperative Management of Patients with Complicated Respiratory Dysfunction].

This article describes the perioperative complications, perioperative risk assessment, and perioperative management of patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease, especially idiopathic pulmonary fibrosis( IPF), which are the leading diseases in respiratory dysfunction. In COPD, testing for forced expiratory volume during the first second and pulmonary diffusing capacity is important and an algorithm for testing has been presented by the Japanese Association for Chest Surgery. Acute exacerbation of IPF is the leading cause of postoperative mortality in Japan, and risk factors are being analyzed. To reduce the occurrence of postoperative complications, it is important to carry out a risk assessment, select appropriate surgical strategy, and implement a well-planned perioperative management.

[An Abscopal Effect after Palliative Radiotherapy in a Patient with a Locally and Lymph Node Recurrent Gastric Cancer].

Radiotherapy is known to have a high local effect for cancer treatment. However, several reports that radiotherapy could stimulate the anti-tumor effect by releasing endogenous signals and cytokines, increasing the presentation of tumor associated antigens on dendritic cells, and proliferating tumor antigen-specific cytotoxic T lymphocytes have been shown. A tumor regression in both non-irradiated and irradiated fields have observed, which is called"abscopal effect". We report a case of the abscopal effect in adenocarcinoma of the stomach with locally and lymph node recurrence after surgery. A 59-year-old Japanese male was diagnosed with residual stomach cancer and underwent total gastrectomy and distal pancreatectomy. Three months after the surgery, a local recurrence and the involvement of para-aortic lymph node were diagnosed using computed tomography. The chemotherapy treatment(S-1, cisplatin, trastuzumab)was prescribed. However, the disease has progressed. Paclitaxel and ramucirumab were given for second-line, nivolumab for third-line and irinotecan for fourth-line. During that, tumor at local recurrent site invaded to the portal vein. The patients received 50 Gy in 25 fractions of radiotherapy. A remarkable reduction of the mass was shown. In addition to this, we observed that spontaneous shrinking of the para-aortic lymph node metastasis, which was located out of the radiation field. We observed a rare radiation-induced abscopal effect. Radiotherapy might represent a potential candidate for a combination with immunotherapy. A combination of immunotherapy as well as chemotherapy with radiotherapy represents a promising therapeutic strategy.

Rational conversion of chromophore selectivity of cyanobacteriochromes to accept mammalian intrinsic biliverdin.

Because cyanobacteriochrome photoreceptors need only a single compact domain for chromophore incorporation and for absorption of visible spectra including the long-wavelength far-red region, these molecules have been paid much attention for application to bioimaging and optogenetics. Most cyanobacteriochromes, however, have a drawback to incorporate phycocyanobilin that is not available in the mammalian cells. In this study, we focused on biliverdin (BV) that is a mammalian intrinsic chromophore and absorbs the far-red region and revealed that replacement of only four residues was enough for conversion from BV-rejective cyanobacteriochromes into BV-acceptable molecules. We succeeded in determining the crystal structure of one of such engineered molecules, AnPixJg2_BV4, at 1.6 Å resolution. This structure identified unusual covalent bond linkage, which resulted in deep BV insertion into the protein pocket. The four mutated residues contributed to reducing steric hindrances derived from the deeper insertion. We introduced these residues into other domains, and one of them, NpF2164g5_BV4, produced bright near-infrared fluorescence from mammalian liver in vivo. Collectively, this study provides not only molecular basis to incorporate BV by the cyanobacteriochromes but also rational strategy to open the door for application of cyanobacteriochromes to visualization and regulation of deep mammalian tissues.

Retrograde mastoidectomy with canal wall reconstruction versus intact canal wall tympanomastoidectomy for cholesteatoma with minimal mastoid extension.

PURPOSE: Appropriate reconstruction of the canal wall or maintenance of the middle ear pressure in cholesteatoma may help in preventing recurrence. Retrograde mastoidectomy with canal wall reconstruction (RMR) can overcome the challenge of a wider canal wall defect or temporal bone immaturity, which possibly increases the recurrence risk. This study compared the outcomes of RMR and intact canal wall tympanomastoidectomy (ICW) for cholesteatomas with minimal mastoid extension and quantitatively evaluate the relationship between anatomical features and recurrence. METHODS: This single-center retrospective cohort study included patients who had undergone primary ICW or RMR for pars flaccida cholesteatoma with minimal mastoid extension from 2009 to 2019. The main outcome measures were anatomical measurements of the shortest distance between the cranial fossa and the upper canal wall (SCU), attic volume, and bony defect area of the canal wall (BDC) on computed tomography; recidivism; and postoperative air-bone gap (ABG). RESULTS: There were no significant differences in the preoperative anatomical factors, recidivism incidence, and postoperative ABG between the RMR (n = 20) and ICW (n = 60) groups. However, the median BDC was significantly greater in the RMR group (58.3 vs. 37.0 mm2). There was no significant difference in the SCU and attic volume between patients with and without recurrence. CONCLUSION: Selection of RMR or ICW may not affect recidivism and hearing outcomes in cholesteatoma with minimal mastoid extension. Bony defect size and attic narrowness were not associated with recurrence. Considering wider visualization and one-staged operation, RMR can be more adaptable than ICW for cholesteatoma with minimal mastoid extension.

Specific antibody deficiency to pneumococcal polysaccharide in a young adult with recurrent respiratory infections: a case report.

Specific antibody deficiency against pneumococcal serotypes was detected in a patient with recurrent episodes of fever. A 21-year-old man presented with a two-month history of recurrent episodes of fever and shaking chills. He was diagnosed with recurrent episodes of pneumonia caused by Streptococcus pneumoniae serotype 19A and treated with amoxicillin. Serotype-specific antibodies were not produced against most of the serotypes, which were consistent with moderate specific antibody deficiency. After pneumococcal 13-valent conjugate vaccination and pneumococcal polysaccharide vaccination, he adequately responded to the infecting serotype with an antibody titer of 1.1 µg/mL. There were eventually no recurrent episodes of fever with pneumonia.

Safety and efficacy of microwave endometrial ablation for patients with previous uterine surgery: a pilot study.

MEA (microwave endometrial ablation) is a treatment that can control hypermenorrhea. With the increase in the number of caesarean sections and myomectomies, an increasing number of patients with MEA have undergone previous incision of the uterine myometrium. Uterine perforation is major complication. Here we compared the incidence of complications and recurrence between groups with or without previous uterine surgery. 35 patients who underwent MEA were enrolled in the study. We assessed the thickness of uterine myometrium by MRI and transvaginal ultrasonography (TV-US). 12 patients (34%) had previous uterine surgery; Among 12 patients with previous uterine surgery, 6 (50%) showed thinning of the myometrium. No patient showed any complications. There was no difference in recurrence rate between two groups (1/12 = 8% and 2/23 = 8%, respectively). MEA can be performed safely and effectively even for patients with previous uterine surgery.IMPACT STATEMENTWhat is already known on this subject? MEA (microwave endometrial ablation) is a treatment that can control hypermenorrhea.A few serious complications have been reported, including uterine perforation and intestinal injury. There have been no collective reports on women with a history of uterine surgery, and the decision to perform MEA and the detailed procedures have not been clarified.What do the results of this study add? No patient who received MEA showed any complication regardless of previous uterine surgery. There was no difference in recurrence rate of hypermenorrhea between groups with and without previous uterine surgery. MEA could be performed safely and effectively in patients with previous uterine surgery preoperative imaging and intraoperative ultrasoundsWhat are the implications of these findings for clinical practice and/or further research? Curently, with the increase in the number of caesarean sections and myomectomies, the increasing number of patients with MEA have undergone previous incision of the uterine myometrium and this causes thinning of the myometrium. MEA can be safely performed without losing any therapeutic effect, even in patients with a history of uterine surgery, by using MRI and TV-US as preoperative evaluations.

[Lung Transplantation at a Low Volume Center].

The number of lung transplantation performed in Japan is extremely low compared to other countries, whereas we have 10 facilities certified as cadaveric lung transplantation in Japan, meaning that there are low volume centers. By August 2021, we performed lung transplantation in 21 cases for 12 years, therefore, our facility should be considered as low volume center. Surgical outcomes at low volume centers are generally considered poor. However, the overall five-year survival rate of total cases was 84.8%, and that of cadaveric cases was 94.4% in our hospital. It was better than the average of about 73% of all facilities in Japan. These data suggested that the accreditation system in Japan is functioning well. On the other hand, there may be a disparity between facilities. At our facility, we are actively performing inverted lung transplantation so as not to lose the opportunity for transplantation, and we have performed it in three cases so far and have achieved good results.

Genetic alterations in squamous cell lung cancer associated with idiopathic pulmonary fibrosis.

Patients with idiopathic pulmonary fibrosis (IPF) are at higher risk of developing lung cancers including squamous cell lung carcinoma (SCC), which typically carries a poor prognosis. Although the molecular basis of cancer development subsequent to IPF has not been fully investigated, we recently reported two epigenetic phenotypes characterized by frequent and infrequent DNA hypermethylation in SCC, and an association of the infrequent hypermethylation phenotype with IPF-associated SCCs. Here, we conducted targeted exon sequencing in SCCs with and without IPF using the Human Lung Cancer Panel to investigate the genetic basis of IPF-associated SCC. SCCs with and without IPF displayed comparable numbers of total mutations (137 ± 22 vs 131 ± 27, P = .5), nonsynonymous mutations (72 ± 14 vs 69 ± 16, P = .5), indels (3.0 ± 3.5 vs 3.0 ± 3.9, P = 1) and synonymous mutations (62 ± 9.1 vs 60 ± 12, P = .5). Signature 1 was the predominant signature in SCCs with and without IPF. SETD2 and NFE2L2 mutations were significantly associated with IPF (44% vs 13%, P = .03 for SETD2; 38% vs 10%, P = .04 for NFE2L2). MYC amplification, assessed by copy number variant analysis, was also significantly associated with IPF (18.8% vs 0%, P = .04). Mutations in TP53 and CDKN2A were observed relatively frequently in SCCs with frequent hypermethylation (P = .02 for TP53 and P = .06 for CDKN2A). Survival analysis revealed that the SETD2 mutation was significantly associated with worse prognosis (P = .04). Collectively, we found frequent involvement of SETD2 and NFE2L2 mutations and MYC amplification in SCCs with IPF, and an association of a SETD2 mutation with poorer prognosis.

First case report of prosthetic valve endocarditis caused by Mycobacterium wolinskyi.

To date, only 26 cases of Mycobacterium wolinskyi infections have been reported in humans. We herein report a first case of prosthetic valve endocarditis due to this organism after cardiovascular surgery. An 82-year-old man presented with repeat episodes of syncope and fever after aortic valve replacement, mitral valve replacement, left atrial appendage closure, and pulmonary vein isolation. Blood cultures maintained in aerobic bottles were repeatedly positive after 90-100 hours, and Gallium scan revealed abnormal accumulations in the sternum and left testis. While colonies formed by culturing the fluid of the parasternal area and blood cultures revealed gram-positive rods, we could not analyze the colony using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF). M. wolinskyi was finally identified on 16S rRNA, hsp65, and rpoB gene sequencing. We treated the patient with multiple antimycobacterial drugs, i.e., amikacin, imipenem, and clarithromycin for 6 weeks, which was changed to oral ciprofloxacin and minocycline for 12 months. This case highlights the need to consider rapidly growing mycobacteria, including M. wolinskyi, if chronic fever persists from weeks to months after surgery, the blood culture is positive, and the organism is not identified. In addition, sequencing the 16S rRNA, hsp65, and rpoB genes is essential for diagnosis.

Posterior reversible encephalopathy syndrome complicating hyperosmolar hyperglycemic syndrome.

Hyperosmolar hyperglycemic syndrome is a life-threatening diabetic emergency that manifests as altered mental status. An otherwise healthy 40-year-old man presented to our emergency department with headache and severe hypertension. Brain magnetic resonance imaging showed evidence of posterior reversible encephalopathy syndrome, a usually reversible neurological syndrome characterized by subcortical vasogenic oedema. This first reported case details posterior reversible encephalopathy syndrome concurrent with hyperosmolar hyperglycemic syndrome. Prompt diagnosis and management were essential to avoid non-reversible consequences.