Dachshund Homolog 1: Unveiling Its Potential Role in Megakaryopoiesis and Bacillus anthracis Lethal Toxin-Induced Thrombocytopenia.

Lethal toxin (LT) is the critical virulence factor of Bacillus anthracis, the causative agent of anthrax. One common symptom observed in patients with anthrax is thrombocytopenia, which has also been observed in mice injected with LT. Our previous study demonstrated that LT induces thrombocytopenia by suppressing megakaryopoiesis, but the precise molecular mechanisms behind this phenomenon remain unknown. In this study, we utilized 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced megakaryocytic differentiation in human erythroleukemia (HEL) cells to identify genes involved in LT-induced megakaryocytic suppression. Through cDNA microarray analysis, we identified Dachshund homolog 1 (DACH1) as a gene that was upregulated upon TPA treatment but downregulated in the presence of TPA and LT, purified from the culture supernatants of B. anthracis. To investigate the function of DACH1 in megakaryocytic differentiation, we employed short hairpin RNA technology to knock down DACH1 expression in HEL cells and assessed its effect on differentiation. Our data revealed that the knockdown of DACH1 expression suppressed megakaryocytic differentiation, particularly in polyploidization. We demonstrated that one mechanism by which B. anthracis LT induces suppression of polyploidization in HEL cells is through the cleavage of MEK1/2. This cleavage results in the downregulation of the ERK signaling pathway, thereby suppressing DACH1 gene expression and inhibiting polyploidization. Additionally, we found that known megakaryopoiesis-related genes, such as FOSB, ZFP36L1, RUNX1, FLI1, AHR, and GFI1B genes may be positively regulated by DACH1. Furthermore, we observed an upregulation of DACH1 during in vitro differentiation of CD34-megakaryocytes and downregulation of DACH1 in patients with thrombocytopenia. In summary, our findings shed light on one of the molecular mechanisms behind LT-induced thrombocytopenia and unveil a previously unknown role for DACH1 in megakaryopoiesis.

False Liver Metastasis by Positron Emission Tomography/Computed Tomography Scan after Chemoradiotherapy for Esophageal Cancer-Potential Overstaged Pitfalls of Treatment.

In patients with esophageal cancer undergoing neoadjuvant chemoradiotherapy (nCRT), subsequent restaging with F-18-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) can reveal the presence of interval metastases, such as liver metastases, in approximately 10% of cases. Nevertheless, it is not uncommon in clinical practice to observe focal FDG uptake in the liver that is not associated with liver metastases but rather with radiation-induced liver injury (RILI), which can result in the overstaging of the disease. Liver radiation damage is also a concern during distal esophageal cancer radiotherapy due to its proximity to the left liver lobe, typically included in the radiation field. Post-CRT, if FDG activity appears in the left or caudate liver lobes, a thorough investigation is needed to confirm or rule out distant metastases. The increased FDG uptake in liver lobes post-CRT often presents a diagnostic dilemma. Distinguishing between radiation-induced liver disease and metastasis is vital for appropriate patient management, necessitating a combination of imaging techniques and an understanding of the factors influencing the radiation response. Diagnosis involves identifying new foci of hepatic FDG avidity on PET/CT scans. Geographic regions of hypoattenuation on CT and well-demarcated regions with specific enhancement patterns on contrast-enhanced CT scans and MRI are characteristic of radiation-induced liver disease (RILD). Lack of mass effect on all three modalities (CT, MRI, PET) indicates RILD. Resolution of abnormalities on subsequent examinations also helps in diagnosing RILD. Moreover, it can also help to rule out occult metastases, thereby excluding those patients from further surgery who will not benefit from esophagectomy with curative intent.

The association between smoking cessation and lifestyle/genetic variant rs6265 among the adult population in Taiwan.

Recent studies showed significant associations between socio-demographic, lifestyle factors, polymorphic variant rs6265, and smoking cessation behaviours. We examined rs6265 TT, TC and CC genotypes and their association with socio-demographic and other variables, including mental health status, drinking, exercise, and smoking behaviour among Taiwanese adults. Data on rs6265 were retrieved from the Taiwan Biobank, which contained genetic data collected between 2008 to 2019 from 20,584 participants (aged 30-70 years). Participants who smoked for more than 6 months prior to enrolment were categorized as smokers. If they had smoked and later quit for more than 6 months, they were classified as former smokers. Information regarding drinking, exercise, depression, and bipolar disorder were obtained through questionnaires and were categorized as either as affirmative (yes) or negative (no) responses. In contrast to previous studies, we found that the association between the polymorphism rs6265 and smoking behaviour was not significant (P-value = 0.8753). Males with lower education levels, young persons, and alcohol drinkers showed significant smoking behaviours (P-value < .0001). This population-based study indicates that rs6265 has no significant correlations with smoking cessation behaviour among adults in Taiwan.

A modified procedure of T-tube maneuver to treat tracheal total obstruction involving ablative bronchoscopy sparing open surgical intervention.

Objectives: The study objectives were to test an innovative T-tube procedure involving ablative bronchoscopy for the treatment of total airway occlusion and to orchestrate a safe and nontraumatic maneuver to treat intricate subglottic stenosis amenable for substituting the conventional surgical intervention. Methods: This was an uncontrolled single-center cohort study on 1254 patients from January 2001 to June 2021. Patients underwent the modified T-tube procedure treatment for tracheal stenosis. Only 42 patients were included in the study because they had full records for subglottic total occlusion sitting tracheostomy. The ablative bronchoscopy, aided by a fixed suspending laryngoscope, was applied to retunnel their total airway occlusion. T-tube revision and removal were conducted under general anesthesia with laryngeal mask airway aid during follow-up. Results: The primary outcome was 90-day mortality. The secondary outcome was 90-day morbidity. The 42 patients included in the study had a mean age of 52.29 years (range, 9-84 years) with 22 men (52.38%). Their mean length of hospital stay was 13.67 days (range, 2-45 days). Their mean operation time was 73 minutes (range, 43-256 minutes). Their mean length of the tracheal stenosis was 2.8 cm (range, 0.8-6.3 cm). Outcomes were good in 29 patients (69.05%), satisfactory in 10 patients (23.81%), and considered failures in 3 patients (7.14%). A total of 16 patients (38.10%) underwent decannulation, and 3 patients (7.14%) were shifted to a Shiley tracheostomy. All 42 patients had a median follow-up of 6.2 years (range, 1.5-16.3 years). Conclusions: The modified T-tube procedure, which offered both resilience and versatility, improved the conventional technique in treating those patients experiencing total tracheal stenosis and who were unqualified for conventional open surgery.

Robotic or transanal total mesorectal excision (TaTME) approach for rectal cancer, how about both? Feasibility and outcomes from a single institution.

Laparoscopic surgery for rectal cancer is technically challenging. Robotic and transanal TME (TaTME) are both novel approaches developed to provide better visualization and dissection. We aim to combine both approaches in a hybrid procedure and evaluate the feasibility as well as patient and oncological outcomes in this study. A review of a prospectively maintained database of patients who underwent a hybrid abdominal robotic approach with TaTME for rectal cancer between January 2016 and October 2018 was undertaken. Patient demographics, tumor characteristics and surgical outcomes were recorded and analyzed. A total of 69 patients (43 males, 26 females) received this hybrid approach. Their median age was 58 years (range 35-87) with a mean BMI of 24.3 kg/m2 (range 16.4-44.2). Median distance from anal verge was 5 cm (range 2-9). The patients had a median hospital length of stay of 7 days (range 5-28). Complication rate was 17.4% (12 patients) with 3 patients (4.3%) requiring a reoperation. TME quality was optimal with all of them either complete (81.2%) or almost complete (18.8%). 65 patients (94.2%) had an R0 resection with 4 patients (5.8%) with involved circumferential resection margins (≤ 1 mm). The median number of lymph nodes harvested was 20 (range 6-37). After a median follow-up of 27.7 months (range 7-42), local recurrence was identified in 2 patients (4%). Three patients (5.2%) had distant recurrence at the 3-year mark. Hybrid robotic abdominal dissection with transanal TME for rectal cancer appears to be feasible with comparable surgical outcomes to other traditional approaches.

Feasibility of in situ chondrogenesis for the entire umbilical cord in preliminary preparation for tracheal graft.

BACKGROUND: There remains a scarcity of both autografts and allografts for tracheal transplantation after long-segmental resection. Subsequently, tissue engineering has become a promising alternative for tracheal transplantation, which requires successful in vitro chondrogenesis. METHODS: To optimize the protocol for in situ chondrogenesis using the pig-derived whole Umbilical Cord (UC) as the starting material, it must be performed without using the UC-multipotent stromal cell (MSCs) isolation procedure. Nevertheless, chondrogenic induction is performed under a variety of conditions; with or without TGF-ß1 at different concentrations, and also in combination with either a rotatory or hollow organ bioreactor. The engineered explant sections were analyzed using various histochemical and immunohistochemical stains to assess the expression of chondrocyte markers. Cell viability was determined through use of the APO-BrdU TUNEL assay kit. RESULTS: The results showed that culture conditions induced heterogeneous chondrogenesis in various compartments of the UC. Moreover, explants cultured with 10 ng/ml TGF-ß1 under hypoxic (1% O2) in combination with a bioreactor, significantly enhanced the expression of aggrecan and type II collagen, but were lacking in the production of Glycosaminoglycans (GAGs), as evidenced by alcian blue staining. We speculated that whole segment UCs allowed for the differentiation into premature chondrocytes in our tissue-engineered environments. CONCLUSION: This study has provided exciting preliminary evidence showing that a stem cell-rich UC wrapped around an anatomical tracheal scaffold and implanted in vivo can induce nodes of new cartilage growth into a structurally functional tissue for the repairing of long-segmental tracheal stenosis.

Empyema thoracis complicated by anaemia as caused by occult bonelet aspiration.

A 62-year-old man was referred to our medical centre with productive cough and high fever over the span of one week, as well as the affiliated symptoms of chronic cough and dizziness for more than six months. Computed tomography (CT) of the thorax was performed and analysed revealing lobulated empyema with thick pleura and two foreign body (FB) retentions in the right lower lobe bronchus. The patient proceeded to thoracoscopic decortications and finalized through retrieval of two dark black stained bonelets with ignored aspiration. After surgery, the patient recovered uneventfully and was discharged in stable condition.

De novo cartilage growth after implantation of a 3-D-printed tracheal graft in a porcine model.

BACKGROUND: Experiments were conducted on the assumption that vivid chondrogenesis would be boosted in vivo following previously preliminary chondrogenesis in a mesenchymal stem cell (MSC)-rich entire umbilical cord (UC) in vitro. METHODS: Virtual 3-D tracheal grafts were generated by using a profile obtained by scanning the native trachea of the listed porcine. Although the ultimate goal was the acquisition of a living specimen beyond a 3-week survival period, the empirical results did not meet our criteria until the 10th experiment, ending with the sacrifice of the animal. The categories retrospectively evolved from post-transplant modification due to porcine death using 4 different methods of implantation in chronological order. For each group, we collected details on graft construction, clinical outcomes, and results from both gross and histology examinations. RESULTS: Three animals died due to tracheal complications: one died from graft crush, and two died secondary to erosion of the larger graft into the great vessels. It appeared that the remaining 7 died of tracheal stenosis from granulation tissue. Ectopic de novo growth of neocartilage was found in three porcine subjects. In the nearby tissues, we detected neocartilage near the anastomosis containing interim vesicles of the vascular canals (VCs), perichondrial papillae (PPs) and preresorptive layers (PRLs), which were investigated during the infancy of cartilage development and were first unveiled in the tracheal cartilage. CONCLUSIONS: 3-D-printed anatomically precise grafts could not provide successful transplantation with stent-sparing anastomosis; nonetheless, de novo cartilage regeneration in situ appears to be promising for tracheal graft adaptability. Further graft refinement and strategies for managing granulated tissues are still needed to improve graft outcomes.

Phantom simulation of liver metastasis on a positron emission tomography with computed tomography scan after neoadjuvant chemoradiotherapy for distal esophageal cancer: a case report.

BACKGROUND: Neoadjuvant chemoradiotherapy is currently the gold standard treatment for esophageal cancer prior to surgery. This radiation therapy will sometimes lead to liver damage parallel to esophageal lesions, which mimics liver metastasis visualized by 18F-fluorodeoxyglucose positron emission tomography with computed tomography. In this report, we publish virtual radiation-induced liver damage images obtained during surgery, along with the coherent pathology, in order to confirm the false-positive result through an optimally decisive radiological examination. CASE PRESENTATION: We report a case of a Asian male patient with distal esophageal cancer who had undergone neoadjuvant chemoradiotherapy (5000 cGy). Subsequently, a new lesion was discovered during a positron emission tomography with computed tomography scan 6 weeks later, near the left caudate lobe of the liver during tumor restaging. To exclude the possibility of liver metastasis, serial imaging was conducted, which included liver sonography, computed tomography, and magnetic resonance imaging for a more intimate probe. The patient's condition was verified as being liver inflammation change, as seen by the liver magnetic resonance imaging presentation. Thoracoscopic esophagectomy was performed with cervical esophagogastrostomy via the retrosternal route, along with a feeding jejunostomy. The procedure was performed smoothly, with an intraoperative liver biopsy also being conducted 2 weeks later, after positron emission tomography with computed tomography restaging. The pathology report revealed esophageal cancer in the form of poorly differentiated squamous cell carcinoma, pT3N1M0. The liver biopsy revealed obvious inflammation change after radiation therapy, which elucidated sinusoidal congestion with the attenuated hepatic cords and filled with erythrocytes. There was no evidence of liver metastasis. The patient recovered uneventfully and was discharged with his oral intake performing smoothly, and a stable condition was observed during 12 months of outpatient department follow-up. CONCLUSIONS: New foci of increased 18F-fluorodeoxyglucose avidity are commonly seen in the caudate and left hepatic lobes of the liver during neoadjuvant chemoradiation for distal esophageal cancer, and these findings generally reflect radiation-induced liver disease rather than metastatic disease. Awareness of the pitfalls of a high 18F-fluorodeoxyglucose uptake in radiation-induced liver injury is crucial in order to avoid misinterpretation and overstaging. Except for the location of 18F-fluorodeoxyglucose uptake, the shape of the lesion, and an maximum standardized uptake value (> 10/h), a convincing liver magnetic resonance imaging scan or even a liver biopsy can provide accurate information for distinguishing radiotherapy-induced liver injury from liver metastasis.

Needs assessment for novel Gram-negative antibiotics in US hospitals: a retrospective cohort study.

BACKGROUND: Evidence-based needs assessments for novel antibiotics against highly-resistant Gram-negative infections (GNIs) are scarce. We aimed to use real-world data from an electronic health record repository to identify treatment opportunities in US hospitals for GNIs resistant to all first-line drugs. METHODS: For this retrospective cohort study, population estimates with an unmet need for novel Gram-negative antibiotics were quantified using the Cerner Health Facts database (2009-15), aggregating episodes of infection in US hospitals with pathogens displaying difficult-to-treat resistance (DTR; resistance to carbapenems, other ß-lactams, and fluoroquinolones) and episodes involving empirical coverage with reserve drugs (colistin or polymyxin B and aminoglycosides). Episodes displaying extended-spectrum cephalosporin resistance (ECR) were also estimated. Episodes were multiplied by site-specific and fixed 14-day treatment durations for conservative and liberal days-of-therapy (DOT) estimates and stratified by site and taxon. Hospital type-specific DOT rates were reliability adjusted to account for random variation; cluster analyses quantified contribution from outbreaks. FINDINGS: Across 2 996 271 inpatient encounters and 134 hospitals, there were 1352 DTR-GNI episodes, 1765 episodes involving empirical therapy with colistin or polymyxin B, and 16 632 episodes involving aminoglycosides. Collectively, these yielded 39·0 (conservative estimate) to 138·2 (liberal estimate) DOT per 10 000 encounters for a novel DTR-GNI-targeted drug, whereas greater treatment opportunities were identified for ECR (six times greater) and ß-lactam susceptible GNIs (70 times greater). The most common DTR-GNI site and pathogen was lower respiratory (14·3 [43·3%] of 33 DOT per 10 000 encounters) and Pseudomonas aeruginosa (522 [38·1%] of 1371 episodes), whereas Enterobacteriaceae urinary-tract infections dominated the ECR or carbapenem-sparing niche (59·0% [5589 of 9535 episodes]) equating to 210·7 DOT per 10 000 encounters. DTR Stenotrophomonas maltophilia, Burkholderia spp, and Achromobacter spp represented less than 1 DOT per 10 000 encounters each. The estimated need for DTR-GNI-targeted antibiotics saw minor contributions by outbreaks and varied from 0·5 to 73·1 DOT per 10 000 encounters by hospital type. INTERPRETATION: Suspected or documented GNIs with no or suboptimal treatment options are relatively infrequent. Non-revenue-based strategies and innovative trial designs are probably essential to the development of antibiotics with improved effectiveness for these GNIs. FUNDING: Center for Drug Evaluation and Research, US Food and Drug Administration; Intramural Research Program, National Institutes of Health Clinical Center and the National Institute of Allergy and Infectious Diseases and the National Cancer Institute.

3-D printing model used to streamline surgical procedures for an intricate condition of airway compression caused by devastating mediastinal chondrosarcoma: a case report.

BACKGROUND: The condition of mediastinal chondrosarcoma causing severe airway compression has never been reported before, and its complexity makes its surgical management challenging. We implemented two new techniques to overcome this problem. Creative mockup analogy of a distorted trachea and tumor lesion using a 3-D printing module, with reprogramming by computed tomography, streamlined the panorama with intricate correlation. CASE PRESENTATION: Our patient was a previously healthy 52-year-old slender yellow man who had no obvious medical history. In the last 3 years, upper respiratory tract infection and productive cough were noted frequently, and the patient's symptoms were aggravated with shortness of breath when his head was positioned below 90 degrees during squatting and hunching of the body. The patient manifested prone sleep with ashen complexion, and he had lost 3-4 kg of body weight over the 3 weeks before admission to our hospital. Virtual bronchoscopy with computed tomography revealed an 8.3 × 7.5 × 4-cm lobulated right upper mediastinal mass with amorphous calcification and severe, intricate airway compression. A creative mockup analogy module of the distorted trachea and tumor was generated by 3-D printing and reprogrammed by computed tomography to streamline the sophisticated correlation. The patient underwent a two-stage operation comprising stabilization of the airway for innovative T-tube insertion preceded by thoracoscopy-assisted radical removal of the tumor. Postoperative adjuvant radiotherapy was administered. The patient recovered uneventfully and stayed healthy for 2 solid years in follow-up. CONCLUSIONS: An advanced 3-D printing model provides affirmative information related to treatment strategy and is also a prospective tool for better doctor-patient communication regarding the disease.

Robotic transanal total mesorectal excision assisted by laparoscopic transabdominal approach: A preliminary twenty-case series report.

BACKGROUND: Laparoscopy-assisted robotic transanal total mesorectal excision is a novel surgical technique for rectal cancer resection. Compared to prior DaVinci Si system case series, this case series is the first to report robotic taTME assisted by laparoscopy (r-taTME) in which the "transanal team" operates via the DaVinci Xi system. As a result, we aim to delineate and discuss preliminary findings from our robotic taTME experiences. METHODS: A total of twenty patients (twelve males) who underwent robotic taTME assisted by laparoscopy (r-taTME) between January 2016 and November 2016 at a single institution were documented. Surgical outcomes, including complications, pathological outcomes, and short-term results, were then retrospectively analyzed. RESULTS: All patients underwent r-taTME via a two-team approach. The "abdominal team" operated via a single port method (ileostomy site), while the "transanal team" operated via the DaVinci Xi system. The mean patient age was 56.7 ± 14.3 years (range 31-79), and the mean distance from tumor to anal verge was 6.0 ± 2.7 cm (range 2-10). The mean estimated intraoperative blood loss was 88 ± 107 ml (range 30-500), and circular stapling was utilized to restore continuity in 80% of study patients. The overall postoperative complication rate was 35%, and the mean distal margin length was 3.1 ± 1.3 cm. There were three patients who had a circumferential margin (CRM) involved by cancer cells (≤1 mm). CONCLUSION: Our preliminary series report demonstrates that utilization of r-taTME assisted by laparoscopy is safe and feasible. Development of a novel transanal approach that allows single-port access alongside a multi-arm robotic system may increase the convenience and efficiency of future operation.

Transanal total mesorectal excision for rectal cancer: hype or new hope?

Rectal cancer has always posed surgical challenges to the colorectal surgeon. The quality of the total mesorectal excision (TME) performed is key in determining local disease control. Unlike the great success in adoption of laparoscopic surgery in colon cancer treatment, studies comparing laparoscopy to open rectal surgery all revealed noninferiority was not achieved. Transanal TME (taTME) is the latest advanced technique pioneered to tackle difficult pelvic dissections. The evolution of taTME surgery in recent years was explored in this review. The outcomes to date on the latest literatures are reviewed, included complications, functional outcomes, oncological results and future clinical researches. taTME, while definitely still in its early stages of development, has steadily accumulated safety and feasibility data. It not only provides a better solution to an old problem that colorectal surgeons have been attempting to tackle for quite some time, but also appears to be quite promising in terms of outcomes on numerous fronts. With structured training models, and proctored clinical application, alongside design and implementation of international-scale large multicenter randomized clinical trials, one can only hope that taTME and its innovations will not only open a new era for colorectal surgery, but also for even more surgical disease pathologies.

Transanal Total Mesorectal Excision Versus Laparoscopic Surgery for Rectal Cancer Receiving Neoadjuvant Chemoradiation: A Matched Case-Control Study.

BACKGROUND: Neoadjuvant chemoradiation therapy (nCRT) has been indicated for locally advanced rectal cancer. While utilization of laparoscopy in rectal cancer surgery has been popular in recent years, tumors receiving nCRT is still a surgical challenge. Transanal total mesorectal excision (TaTME) has emerged as a focused area of laparoscopic surgery that is becoming an increasingly acceptable approach in the field of rectal surgery. METHODS: Between December 2013 and April 2015, a total of 50 patients (38 males) with post-nCRT middle or lower rectal cancer who then underwent TaTME at two separate institutions were prospectively documented. Overall, 100 matched control cohorts who received conventional laparoscopic rectal surgery (LapTME) were simultaneously retrieved from a prospectively registered database. Four parameters of sex, age, clinical stage, and American Society of Anesthesiologists (ASA) score were matched for surgical outcomes, and short-term oncological results, including complications and pathological outcomes, were analyzed. RESULTS: Both the TaTME and LapTME groups received 5-fluorouracil-based chemotherapy and 5 weeks of long-course radiation therapy. Mean operative time for the TaTME group was 182.1 ± 55.4 min (156.6 ± 37.8 min in two-team-approach cases) and 178.7 ± 34.8 min for the LapTME group. The TaTME group yielded longer distal margin lengths. No significant differences were observed in blood loss, intraoperative complication rate, conversion rate, anastomosis type, and free circumferential margin rate. CONCLUSION: This matched case-control study demonstrated that TaTME is safe and feasible. Compared with LapTME, TaTME not only achieves identical circumferential margin status without compromising other operative and quality parameters but also benefits patients by achieving a longer distal margin. Thus, TaTME has the potential to become an option in managing irradiated rectal cancer.