Development of a Prognostic Scoring System for Tracheostomized Patients Requiring Prolonged Ventilator Care: A Ten-Year Experience in a University-Affiliated Tertiary Hospital.

Background and Objectives: This study aimed to assess the value of a novel prognostic model, based on clinical variables, comorbidities, and demographic characteristics, to predict long-term prognosis in patients who received mechanical ventilation (MV) for over 14 days and who underwent a tracheostomy during the first 14 days of MV. Materials and Methods: Data were obtained from 278 patients (66.2% male; median age: 71 years) who underwent a tracheostomy within the first 14 days of MV from February 2011 to February 2021. Factors predicting 1-year mortality after the initiation of MV were identified by binary logistic regression analysis. The resulting prognostic model, known as the tracheostomy-ProVent score, was computed by assigning points to variables based on their respective ß-coefficients. Results: The overall 1-year mortality rate was 64.7%. Six factors were identified as prognostic indicators: platelet count < 150 × 103/µL, PaO2/FiO2 < 200 mmHg, body mass index (BMI) < 23.0 kg/m2, albumin concentration < 2.8 g/dL on day 14 of MV, chronic cardiovascular diseases, and immunocompromised status at admission. The tracheostomy-ProVent score exhibited acceptable discrimination, with an area under the receiver operating characteristic curve (AUC) of 0.786 (95% confidence interval: 0.733-0.833, p < 0.001) and acceptable calibration (Hosmer-Lemeshow chi-square: 2.753, df: 8, p = 0.949). Based on the maximum Youden index, the cut-off value for predicting mortality was set at ≥2, with a sensitivity of 67.4% and a specificity of 76.3%. Conclusions: The tracheostomy-ProVent score is a good predictive tool for estimating 1-year mortality in tracheostomized patients undergoing MV for >14 days. This comprehensive model integrates clinical variables and comorbidities, enhancing the precision of long-term prognosis in these patients.

Ability of the modified NUTRIC score to predict mortality in patients requiring short-term versus prolonged acute mechanical ventilation: a retrospective cohort study.

BACKGROUND: The modified NUTRIC (nutritional risk in the critically ill) score has been reported to predict clinical outcomes in critically ill patients. However, the applicability of this score may differ between patients undergoing short-term mechanical ventilation (STMV, < 96 h) and those undergoing prolonged acute mechanical ventilation (PAMV, ⩾96 h), as PAMV patients typically experience significantly higher morbidity and mortality. OBJECTIVE: This study aimed to investigate the predictive ability of modified NUTRIC score for predicting 28-day mortality in patients receiving STMV and PAMV. DESIGN: Retrospective single-center cohort study. METHODS: We enrolled patients who received mechanical ventilation (MV) on the day of admission to the intensive care unit (ICU) from 1 December 2015 to 30 November 2020. Modified NUTRIC scores were calculated based on the clinical data of each patient at ICU admission. RESULTS: The study population comprised 464 patients, including 319 (68.8%) men with a mean age of 69.7 years. Among these patients, 132 (28.4%) received STMV and 332 (71.6%) received PAMV. The overall 28-day mortality rate was 26.7%, which was significantly higher in STMV patients than in PAMV patients (37.9% versus 22.3%, p < 0.001). Evaluation of the predictive performance of the modified NUTRIC score for 28-day mortality revealed areas under the receiver operating characteristic curves of 0.672 [95% confidence interval (CI): 0.627-0.714] for total patients, 0.819 (95% CI, 0.742-0.880) for STMV patients, and 0.595 (95% CI, 0.540-0.648) for PAMV patients. The best overall cutoff value was 5 in total, STMV, and PAMV patients. This cutoff value was a significant predictor of 28-day mortality based on the Cox proportional hazard model for total [hazards ratio (HR): 2.681; 95% CI: 1.683-4.269] and STMV (HR: 5.725; 95% CI: 2.057-15.931) patients, but not for PAMV patients. CONCLUSION: The modified NUTRIC score is more effective in predicting 28-day mortality in patients undergoing STMV than in those undergoing PAMV.

Predicting survival: Modified NUTRIC score in short-term vs. prolonged mechanical ventilationIn this study, we examined the scoring system called the Modified NUTRIC (nutritional risk in the critically ill) score to determine whether it could be used to predict 28-day mortality following Intensive Care Unit (ICU) admission. In particular, we wanted to determine whether the score works equally well for patients who need short-term mechanical ventilation (STMV, less than 96 hours) and those who need prolonged acute mechanical ventilation (PAMV, 96 hours or more). PAMV patients tend to have more severe illness and use more medical resources.Here's what we did: We studied 464 patients who were put on a breathing machine (mechanical ventilation) on the same day they were admitted to the ICU between December 1, 2015, and November 30, 2020.We calculated the Modified NUTRIC (m-NUTRIC) scores based on their medical information when they entered the ICU.We found that the overall 28-day mortality was 26.7%, and that it was higher for STMV patients (37.9%) than for PAMV patients (22.3%).When we checked how well the m-NUTRIC score predicted survival, we discovered that it worked better for STMV patients (with an accuracy of 81.9%) than for PAMV patients (with an accuracy of 59.5%).We also found that a m-NUTRIC score of 5 or more points was indicative of a higher mortality in STMV patientsIn conclusion, the m-NUTRIC score is a more reliable predictor of 28-day survival in patients who need short-term mechanical ventilation than in those who need prolonged acute mechanical ventilation.

Bronchial Washing Using a Thin Versus a Thick Bronchoscope to Diagnose Pulmonary Tuberculosis: A Randomized Trial.

BACKGROUND: This study was performed to evaluate the efficacy of using a thin bronchoscope for the diagnosis of pulmonary tuberculosis (PTB). METHODS: Between March 2019 and November 2021, we prospectively enrolled participants with suspected PTB whose sputum acid-fast bacilli (AFB) smear and tuberculosis (TB) polymerase chain reaction (PCR) tests were negative or who could not produce self-expectorated sputum. Participants were randomized to a control group (bronchial washing [BW] using a 5.9-mm conventional bronchoscope guided by chest computed tomography) or an investigational group (BW using a 4.0-mm thin bronchoscope under virtual bronchoscopic navigation guidance). The primary outcome was detection of TB in BW fluid, defined as a positive result in the Xpert MTB/RIF assay. The secondary outcomes included AFB smear and Mycobacterium tuberculosis culture positivity, time to treatment initiation, and bronchoscopy-related complications. RESULTS: In total, 85 participants were included in the final analysis (43 in the control group and 42 in the investigational group). Twenty-three and 29, respectively, were finally diagnosed with PTB. The TB detection rate in BW fluid was higher in the investigational group (72.4% vs 43.5%, P = .035). Mycobacterium tuberculosis culture positivity was also higher in the investigational group (79.3% vs 52.2%, P = .038). No participants required premature bronchoscopy termination because of complications. Of the participants with PTB, the time to treatment initiation was shorter in the investigational group (median, 2.0 days vs 4.0 days, P = .001). CONCLUSIONS: BW using a thin bronchoscope increases the TB detection rate in patients with PTB compared to conventional bronchoscopy. Clinical Trials Registration.ȃNCT03802812.

A Predictive Model for Dysphagia after Ventilator Liberation in Severe Pneumonia Patients Receiving Tracheostomy: A Single-Center, Observational Study.

The main purpose of this study was to develop a model predictive of dysphagia in hospital survivors with severe pneumonia who underwent tracheostomy during their hospital stay. The present study included 175 patients (72% male; mean age, 71.3 years) over 5 years. None of these patients had a history of deglutition disorder before hospital admission. Binary logistic regression analysis was performed to identify factors predicting dysphagia at hospital discharge. Dysphagia scores were calculated from ß-coefficients and by assigning points to variables. Of the enrolled patients, 105 (60%) had dysphagia at hospital discharge. Factors prognostic of dysphagia at hospital discharge included being underweight (body mass index < 18.5 kg/m2), non-participation in a dysphagia therapy program, mechanical ventilation ≥ 15 days, age ≥ 74 years, and chronic neurologic diseases. Underweight and non-participation in a dysphagia therapy program were assigned +2 points and the other factors were assigned +1 point. Dysphagia scores showed acceptable discrimination (area under the receiver operating characteristic curve for dysphagia 0.819, 95% confidence interval: 0.754−0.873, p < 0.001) and calibration (Hosmer−Lemeshow chi-square = 9.585, with df 7 and p = 0.213). The developed dysphagia score was predictive of deglutition disorder at hospital discharge in tracheostomized patients with severe pneumonia.

Is it worth applying self-irrigation after third molar extraction? A randomised controlled trial.

In this study, we aimed to examine the effectiveness of self-irrigation following the extraction of mandibular third molars. A randomised controlled clinical trial was conducted with 155 patients who had undergone extraction of a mandibular third molar. The irrigation group was instructed to self-irrigate the extraction socket with tap water using a syringe three times a day, starting seven days after the tooth extraction. The incidence of complications and mouth opening, halitosis, plaque/gingival index, and oral health-related quality of life (OHRQoL) were measured. The irrigation group showed a lower incidence of complications than the non-irrigation group. The halitosis, plaque, and gingival scores were lower by mean (SD) 19.66 (5.19), 0.58 (0.06), and 0.62 (0.08), respectively, in the irrigation group than in the non-irrigation group (p = 0.0001). A greater amount of food packing was associated with higher halitosis, plaque, and gingival scores and poorer OHRQoL (p < 0.05). Further, more frequent irrigation was associated with lower halitosis, plaque, and gingival scores and better OHRQoL (p ≤ 0.016). Self-irrigation of the extraction socket using a syringe containing tap water is a very effective method for keeping the extraction socket clean. This technique reduced halitosis, improved plaque and gingival indices, and increased OHRQoL.

Optimal application of compressive palatal stents following mesiodens removal in pediatric patients: A Randomized Controlled Trial / Aplicación óptima de stents palatinos de compresión después de la extracción del mesiodens en pacientes pediátricos: un ensayo controlado aleatorio

Background: There is no scientific evidence supporting the choice of a palatal stent in patients who underwentremoval of an impacted supernumerary tooth. We aimed to investigate the effects of palatal stents in patients whounderwent supernumerary tooth removal through a palatal approach and to suggest the optimal stent thicknessand material.Material and Methods: We recruited 144 patients who underwent extraction of a supernumerary tooth between themaxillary anterior teeth. Subjects were assigned to a control group (CG) or one of four compressive palatal stentgroups (CPSGs) classified by the thickness and material of the thermoplastic acrylic stent used. Palatal gingivalswelling and objective indices (healing, oral hygiene, gingival, and plaque) were evaluated before surgery and onpostoperative days (PODs) 3, 7, and 14; pain/discomfort and the Child Oral Health Impact Profile (COHIP) wereassessed as subjective indices of the effects of the stent.Results: The CPSGs showed faster healing than did the CG on PODs 7 (P<0.001) and 14 (P=0.043); swelling wasmeasured by 1.64±0.88 mm and 4.52±0.39 mm, respectively. Although swelling was least in the 4-mm hard group(0.92±0.33 mm), the difference compared with that in the 2-mm hard group (1.01±0.18 mm) was not significant(P=0.077). The CPSGs showed better COHIP (P<0.001-0.036) and pain scores (P<0.001) than did the CG onPODs 1-3. Conclusions: Compressive palatal stents reduce discomfort by decreasing pain and alleviating swelling. Althougha stent is effective regardless of its thickness and material, 2-mm hard stents maximized such positive effects withminimal discomfort.(AU)

Complications associated with specific characteristics of supernumerary teeth.

OBJECTIVES: The purpose of this study was to identify the characteristics of supernumerary teeth, analyze the associated complications, and to present new clinical knowledge on surgical interventions for supernumerary teeth. STUDY DESIGN: This retrospective cohort study was based on the medical records and radiographic records of patients who underwent surgical extraction of supernumerary teeth. The relationships among the patient's age, gender, anatomic features of supernumerary teeth, and presence and type of complications (i.e., spacing, rotation, delayed eruption of the adjacent tooth, cyst formation.) were investigated. The groups were compared by using the Mann-Whitney U test, the Kolmogorov-Smirnov test, and multiple logistic regression analysis (P < .05). RESULTS: The study population consisted of 705 participants who underwent extraction for 1036 supernumerary teeth. The mean age of the participants was 11.5 years, and 73.5% of the participants were males. The complication rate was 55.6%. Variables associated with an increased risk of complications were the patient's age, dentition, tuberculate shape, and horizontal direction of eruption (P < .05). CONCLUSIONS: An increase in the patient's age or abnormalities in the shape and direction of eruption of supernumerary teeth was associated with complications. These parameters should be considered while formulating the treatment plan.

The implication of FLT3 amplification for FLT targeted therapeutics in solid tumors.

We investigated the patients with solid cancers harboring Fms-like tyrosine kinase 3 (FLT3) amplification using targeted sequencing of tumor tissue specimen and FISH assay. Simultaneously, FLT3-amplified patient-derived cells (PDCs) were generated to evaluate the sensitivity to FLT3 inhibition. A patient with metastatic colon cancer who was previously treated with more than 3rd line cytotoxic chemotherapy was found to have FLT3 amplification and then received regorafenib showing partial response. In two PDC cell lines with FLT3 amplification, FLT3 mRNA expression was increased, however, the growth of tumor cells was not significantly inhibited by either regorafenib or sorafenib which is known to block the activity FLT3. Additional drug combinations with mTOR inhibitor did not affect the cell proliferation of PDC. FLT3 amplification in solid cancers is infrequently observed using targeted genomic profile, as yet, FLT3 amplification does not seem to be an actionable target or a proper biomarker for FLT3 inhibitor sensitivity.

Genomic Alterations in Biliary Tract Cancer Using Targeted Sequencing.

BACKGROUND: Biliary tract cancers (BTCs) are rare and heterogeneous group of tumors classified anatomically into intrahepatic and extrahepatic bile ducts and gallbladder adenocarcinomas. Patient-derived tumor cell (PDC) models with genome analysis can be a valuable platform to develop a method to overcome the clinical barrier on BTCs. MATERIAL AND METHODS: Between January 2012 and June 2015, 40 BTC patients' samples were collected. PDCs were isolated and cultured from surgical specimens, biopsy tissues, or malignant effusions including ascites and pleural fluid. Genome analysis using targeted panel sequencing as well as digital multiplexed gene analysis was applied to PDCs as well as primary tumors. RESULTS: Extrahepatic cholangiocarcinoma (N=15, 37.5%), intrahepatic cholangiocarcinoma (N=10, 25.0%), gallbladder cancer (N=14, 35.0%), and ampulla of Vater cancer (N=1, 2.5%) were included. We identified 15 mutations with diverse genetic alterations in 19 cases of BTC from primary tumor specimens. The most common molecular alterations were in TP53 (8/19, 42.1%), including missense mutations such as C242Y, E285K, G112S, P19T, R148T, R248Q, and R273L. We also detected two NRAS mutations (G12C and Q61L), two KRAS mutations (G12A and G12S), two ERBB2 mutations (V777L and pM774delinsMA) and amplification, and three PIK3CA mutations (N345K, E545K, and E521K). PDC models were successfully established in 27 of 40 samples (67.5%), including 22/24 from body fluids (91.7%) and 5/16 from tissue specimens (31.3%). CONCLUSIONS: PDC models are promising tools for uncovering driver mutations and identifying rational therapeutic strategies in BTC. Application of this model is expected to inform clinical trials of drugs for molecular-based targeted therapy.

Molecular characterization of colorectal cancer patients and concomitant patient-derived tumor cell establishment.

BACKGROUND: We aimed to establish a prospectively enrolled colorectal cancer (CRC) cohort for targeted sequencing of primary tumors from CRC patients. In parallel, we established collateral PDC models from the matched primary tumor tissues, which may be later used as preclinical models for genome-directed targeted therapy experiments. RESULTS: In all, we identified 27 SNVs in the 6 genes such as PIK3CA (N = 16), BRAF (N = 6), NRAS (N = 2), and CTNNB1 (N = 1), PTEN (N = 1), and ERBB2 (N = 1). RET-NCOA4 translocation was observed in one out of 105 patients (0.9%). PDC models were successfully established from 62 (55.4%) of the 112 samples. To confirm the genomic features of various tumor cells, we compared variant allele frequency results of the primary tumor and progeny PDCs. The Pearson correlation coefficient between the variants from primary tumor cells and PDCs was 0.881. METHODS: Between April 2014 and June 2015, 112 patients with CRC who underwent resection of the primary tumor were enrolled in the SMC Oncology Biomarker study. The PDC culture protocol was performed for all eligible patients. All of the primary tumors from the 112 patients who provided written informed consent were genomically sequenced with targeted sequencing. In parallel, PDC establishment was attempted for all sequenced tumors. CONCLUSIONS: We have prospectively sequenced a CRC cohort of 105 patients and successfully established 62 PDC in parallel. Each genomically characterized PDCs can be used as a preclinical model especially in rare genomic alteration event.

New cytotoxic sulfated saponins from the starfish Certonardoa semiregularis.

Two new sulfated saponins designated as certonardosides P2 and I3 (1 and 2) were isolated from the brine shrimp active fraction of the MeOH extract of the starfish Certonardoa semiregularis. The structures were determined on the basis of spectral analysis. Compounds 1 and 2 were tested for cytotoxicity against five human tumor cell lines (A549, SK-OV-3, SK-MEL-2, XF498, and HCT15), and compound 1 displayed significant cytotoxicity against the SK-MEL-2 skin cancer cell.

Additional cytotoxic sterols and saponins from the starfish certonardoa semiregularis.

Twelve new (1-7, 9-13) polyhydroxysterols and two new saponins (14 and 15) were isolated from the starfish Certonardoa semiregularis by activity-guided fractionation. Compounds 1-7 are rare examples of 15-keto steroids from starfish. The side chain of compound 11 was also unprecedented in nature. The structures were determined by combined spectroscopic methods and chemical derivatization. These compounds were evaluated for cytotoxicity against a small panel of human solid tumor cell lines, and most of them exhibited considerable activity. One of the 15-keto sterols (6) displayed the highest potency, which is comparable to that of doxorubicin.