A case report of drug interaction between co-packaged nirmatrelvir-ritonavir and tacrolimus causing hyponatremia in a lung transplant recipient.

BACKGROUND: Coronavirus disease 2019 (COVID-19) infection in lung transplant recipients can be lethal owing to the use of immunosuppressants. Antiviral agents may be administered to these patients. Co-packaged nirmatrelvir-ritonavir is a new agent currently being used in combination. CASE PRESENTATION: In this report, we present a case of a 64-year-old woman, a lung transplant recipient, who experienced hyponatremia and showed a high serum tacrolimus concentration following the administration of the co-packaged nirmatrelvir-ritonavir combination. CONCLUSION: Although the nirmatrelvir-ritonavir and tacrolimus combination is not contraindicated, other treatment strategies should be considered first, if available, and the dose of tacrolimus should be reduced when using the nirmatrelvir-ritonavir combination. In cases where combination therapy is necessary, serum tacrolimus levels should be closely monitored in lung transplant recipients. Documentation of more such reports is important to identify drug interactions between nirmatrelvir-ritonavir and other agents, with the aim of preventing severe adverse effects.

The impact of surgical learning curve on short-term outcomes after bilateral lung transplantation: results from a multidisciplinary surgical team.

OBJECTIVES: The aim of this study was to examine the impact of surgical learning curve on short-term clinical outcomes of patients after bilateral lung transplantation (LTx) performed by a surgical multidisciplinary team (MDT). METHODS: Forty-two patients underwent double LTx from December 2016 to October 2021. All procedures were performed by a surgical MDT in a newly established LTx program. The time required for bronchial, left atrial cuff and pulmonary artery anastomoses was the main end point to assess surgical proficiency. The associations between the surgeon's experience and procedural duration were examined by linear regression analysis. We employed the simple moving average technique to generate learning curves and evaluated short-term outcomes before and after achieving surgical proficiency. RESULTS: Both total operating time and total anastomosis time were inversely associated with the surgeon's experience. On analysing the learning curve for bronchial, left atrial cuff and pulmonary artery anastomoses using moving averages, the inflection points occurred at 20, 15 and 10 cases, respectively. To assess the learning curve effect, the study cohort was divided into early (cases 1-20) and late (cases 21-42) groups. Short-term outcomes-including intensive care unit stay, in-hospital stay and severe complications-were significantly more favourable in the late group. Furthermore, there was a notable tendency for patients in the late group to experience a decreased duration of mechanical ventilation along with reduced instances of grade 3 primary graft dysfunction. CONCLUSIONS: A surgical MDT can perform double LTx safely after 20 procedures.

Esophageal stenting with minimally-invasive surgical intervention for delayed spontaneous esophageal perforation.

Background: Spontaneous esophageal perforation is a challenging surgical emergency with significant morbidity and mortality, and timely primary repair carries good outcomes. However, direct repair for a delayed spontaneous esophageal perforation is not always feasible and is associated with high mortality. Esophageal stenting can provide therapeutic benefits in the management of esophageal perforations. In this study, we review our experience with placing esophageal stents in combination with minimally-invasive surgical drainage to treat delayed spontaneous esophageal perforations. Methods: We retrospectively analyzed patients with delayed spontaneous esophageal perforations between September 2018 and March 2021. All patients were treated using a hybrid approach, including esophageal stenting across the gastroesophageal junction (GEJ) to reduce continued contamination, gastric decompression with extraluminal sutures to prevent stent migration, early enteral nutrition, and aggressive minimally-invasive thoracoscopic debridement and drainage of infected material. Results: There were 5 patients with delayed spontaneous esophageal perforation treated with this hybrid approach. The mean duration between symptoms and diagnosis was 5 days, and the interval between symptoms and esophageal stent insertion was 7 days. The median time to oral nutrition and to esophageal stent removal was 43 and 66 days. There was no stent migration or hospital mortality. Three patients (60%) had postoperative complications. All patients were successfully resumed on oral nutrition with esophageal preservation. Conclusions: A hybrid approach combining endoscopic esophageal stent placement with extraluminal sutures to prevent stent migration, thoracoscopic decortication with chest tube drainage, gastric decompression, and jejunostomy tube placement for early nutrition was feasible and effective in the treatment of delayed spontaneous esophageal perforations. This technique offers a less invasive treatment approach for a challenging clinical problem which has traditionally carried a high rate of morbidity and mortality.

Novel Biodegradable 3D-Printed Analgesics-Eluting-Nanofibers Incorporated Nuss Bars for Therapy of Pectus Excavatum.

A novel hybrid biodegradable Nuss bar model was developed to surgically correct the pectus excavatum and reduce the associated pain during treatment. The scheme consisted of a three-dimensional (3D) printed biodegradable polylactide (PLA) Nuss bar as the surgical implant and electrospun polylactide-polyglycolide (PLGA) nanofibers loaded with lidocaine and ketorolac as the analgesic agents. The degradation rate and mechanical properties of the PLA Nuss bars were characterized after submersion in a buffered mixture for different time periods. In addition, the in vivo biocompatibility of the integrated PLA Nuss bars/analgesic-loaded PLGA nanofibers was assessed using a rabbit chest wall model. The outcomes of this work suggest that integration of PLA Nuss bar and PLGA/analgesic nanofibers could successfully enhance the results of pectus excavatum treatment in the animal model. The histological analysis also demonstrated good biocompatibility of the PLA Nuss bars with animal tissues. Eventually, the 3D printed biodegradable Nuss bars may have a potential role in pectus excavatum treatment in humans.

Vicryl Mesh Coverage Reduced Recurrence After Bullectomy for Primary Spontaneous Pneumothorax.

BACKGROUND: Although thoracoscopic stapled bullectomy is a standard procedure for primary spontaneous pneumothorax (PSP), the postoperative recurrence rate is high. We investigated whether using a Vicryl (Ethicon, Somerville, NJ) mesh to cover the staple line after bullectomy reduces the postoperative recurrence rate. METHODS: Our single-blind, parallel-group, prospective, randomized controlled trial at 2 medical centers in Taiwan studied patients with PSP who were aged 15 to 50 years and required thoracoscopic bullectomy. On the day of operation, patients were randomly assigned (1:1) to receive Vicryl mesh (mesh group) or not (control group) after thoracoscopic bullectomy with linear stapling and mechanical apical pleural abrasion. Randomization was achieved using computer-generated random numbers in sealed envelopes. Our primary end point was the pneumothorax recurrence rate within 1 year after the operation (clinicaltrials.gov number, NCT01848860.) RESULTS: Between June 2013 and March 2016, 102 patients were assigned to the mesh group and 102 to the control group. Within 1 year after operation, recurrent pneumothorax was diagnosed in 3 patients (2.9%) in the mesh group compared with 16 (15.7%) in the control group (P = .005). The short-term postoperative results and hospitalization duration were comparable between the groups. CONCLUSIONS: For thoracoscopic bullectomy with linear stapling and mechanical apical pleural abrasion, the use of a Vicryl mesh to cover the staple line is effective for reducing the postoperative recurrence of pneumothorax. Vicryl mesh coverage can be considered an optimal adjunct to the standard surgical procedure for PSP.

Extended pain relief achieved by analgesic-eluting biodegradable nanofibers in the Nuss procedure: in vitro and in vivo studies.

BACKGROUND: The most common complaint after the Nuss procedure is severe postoperative chest pain. The aim of this study was to evaluate the effectiveness of analgesic-eluting biodegradable nanofibers in pain relief after the Nuss procedure. MATERIALS AND METHODS: Poly(d,l)-lactide-co-glycolide, lidocaine, and ketorolac were dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol. This solution was electrospun into a nanofibrous membrane. The elution method and high-performance chromatography were used to characterize the in vitro drug release. Stainless steel bars with and without coating of the analgesic-eluting nanofibrous membrane were implanted underneath the sternums of New Zealand white rabbits. The in vivo characteristics were further investigated. RESULTS: The in vitro study showed that the biodegradable nanofibers released high doses of lidocaine and ketorolac within 10 days. The in vivo study demonstrated high local and systemic concentrations of lidocaine and ketorolac. The serum creatinine level was unaffected. Animals that received implants of the analgesic-eluting nanofiber-coated stainless steel bar exhibited significantly greater food and water ingestion and physical activity than the control group did, indicating effective pain relief. CONCLUSION: The proposed analgesic-eluting biodegradable nanofibers contribute to the achievement of extended pain relief after the Nuss procedure, without obvious adverse effects, in an animal model.

Clinical use of near-infrared fluorescence imaging with indocyanine green in thoracic surgery: a literature review.

Invisible near-infrared (NIR) fluorescence imaging with indocyanine green (ICG) has advantage in detecting for certain anatomy. The method is currently used in some types of surgery, such as sentinel lymph node (SLN) mapping, intraoperative solid tumor identification, and organ perfusion assessment. However, the literature of clinical application in thoracic surgery is lacking. This paper presents the advantages, current applications and potential developments of NIR fluorescence imaging with ICG in thoracic surgery.

Comparative Short-Term Clinical Outcomes of Mediastinum Tumor Excision Performed by Conventional VATS and Single-Port VATS: Is It Worthwhile?

Single-port video-assisted thoracoscopic surgery (VATS) has been widely applied recently. However, there are still only few reports describing its use in mediastinum tumor resection. We present the technique of single-port video-assisted thoracoscopic mediastinum tumor resection and compare it with conventional VATS with regard to short-term outcome.We retrospectively enrolled 105 patients who received mediastinum surgery in Chang Gung Memorial Hospital. Sixteen patients received sternotomy or thoracotomy, 29 patients received single-port VATS, and 60 patients received conventional VATS (3 ports). The operative time, blood loss, postoperation day 1 pain score, discharge day pain score, and postoperative hospital stay were compared. In order to establish a well balanced cohort study, we also use propensity scores match (1:1) to compare the short-term clinical outcome in 2 groups.No operative deaths occurred in this study. Single-port VATS was associated with shorter operative time, lower postoperation day 1 pain score, and shorter postoperation hospital stay in our cohort study (P = 0.001, <0.001, and 0.039), and propensity scores matched cohort study (P = 0.003, <0.001, and <0.001).Single-port VATS for mediastinum tumor appears to be a safe and promising technique with short-term outcome not inferior to conventional VATS in our cohort study. The long-term oncology outcome may require time and more enrolled patients to be further evaluated.

Single-port video-assisted thoracoscopic mediastinal tumour resection.

OBJECTIVES: To present the technique of single-port video-assisted thoracoscopic mediastinal tumour resection, which includes limited thymectomy, extended thymectomy, cyst excision and posterior mediastinal tumour excision, and the early results of resection with the use of this technique. METHODS: Twenty-nine patients with mediastinal tumours were treated with single-port thoracoscopic mediastinal resection at Chung Gung Memorial Hospital between April 2014 and May 2015.The surgical intervention was performed through the fourth or fifth intercostal space at the anterior axillary line. A 5- or 10-mm 30° video camera and working instruments were employed simultaneously at this incision site throughout the surgery. The perioperative variables and outcomes were collected and analysed retrospectively. RESULTS: Among the 29 cases included in the final analysis, 8 extended thymectomies, 5 limited thymectomies, 7 cyst excisions and 9 tumour excisions were performed successfully without the need for conversion. For the 29 patients who underwent single-port video-assisted thoracoscopic surgery (VATS), the mean operation time was 97.3 ± 31.2 min and the average blood loss was 34.1 ± 45.7 ml. The average length of the incision wound was 3.41 ± 0.76 cm and the average length of postoperative hospital stay was 3.75 ± 1.53 days. There were no mortalities, and mobility was achieved 30 days after surgery. CONCLUSIONS: With regard to oncological concerns, the occurrence of postoperative myasthenia gravis or freedom from tumour recurrence is a paramount issue. Our cohort follow-up time was not long enough to address this, and more time and patients are needed for further evaluation. But our preliminary report showed that uniportal VATS for mediastinal tumour resection was a promising and safe technique with regard to short-term clinical outcome.

Prognostic significance of lymphovascular invasion in patients with esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy.

OBJECTIVE: To investigate the prognostic significance of lymphovascular invasion (LVI) in patients with esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant chemoradiotherapy (nCRT). METHODS: We retrospectively reviewed the charts of 416 consecutive patients with ESCC who underwent surgical resection following nCRT at the Chang Gung Memorial Hospital between 1998 and 2008. After exclusion of patients with non-R0 resection or showing no residual tumor (ypT0Nx), the histological tumor sections of 231 patients were reviewed for LVI. Univariate and multivariate analyses were used to identify the independent predictors of overall survival (OS). RESULTS: LVI was observed in 85 patients (36.8 %). The presence of LVI was related to close circumferential resection margins (CRMs), a greater depth of invasion, poor tumor differentiation, and an increased occurrence of lymph node metastases (LNM). The 5 year OS was significantly lower (10 %) in patients with LVI than in those without (31 %; p < 0.001). By multivariate Cox regression analyses, LVI (hazard ratio [HR] 1.5; p = 0.002) and LNM (HR 1.6; p = 0.007) were identified as independent adverse prognostic factors for OS. The 5 year OS rates according to the number of risk factors present were 35, 21, 20, and 5 for LVI(-)LNM(-), LVI(+)LNM(-), LVI(-)LNM(+), and LVI(+)LNM(+) patients, respectively (p < 0.001). CONCLUSIONS: The presence of LVI is independently associated with shorter OS in ESCC patients receiving nCRT. Links between LVI and LNM may provide new clues for the prognostic stratification of esophageal cancer.

Caspr2 antibody limbic encephalitis is associated with Hashimoto thyroiditis and thymoma.

BACKGROUND: Contactin-associated protein 2 (Caspr2) antibody is a neuronal surface antibody (NSAb) capable of causing disorders involving central and peripheral nervous systems (PNS). Thymoma can be found in patients with Caspr2 antibodies and is most frequently associated with PNS symptoms. Myasthenia gravis can be found in these patients, but Hashimoto thyroiditis (HT) has not been reported. METHODS: A 76-year-old woman presented with sub-acute-onset changes in mental status. Further investigations revealed thymoma and HT. The presence of NSAb was tested by immunofluorescence on human embryonic kidney-293 cells. Treatment included corticosteroids, azathioprine, thyroxine, plasmapheresis, and thymectomy. RESULTS: Caspr2 antibody was positive in serum but absent in CSF. Brain magnetic resonance imaging (MRI) showed diffuse cortical atrophy, but did not change significantly after treatments. Brain positron emission tomography (PET) revealed diffuse hypometabolism over the cerebral cortex. The patient's mental status only partially improved. CONCLUSIONS: In Caspr2 antibody-associated syndromes, thymoma can occur in patients presenting only with LE, and HT can be an accompanying disease. Brain MRI and PET may not show specific lesions in limbic area. Patients with Caspr2 antibodies and thymoma may not have good prognosis.

Interval between neoadjuvant chemoradiotherapy and surgery for esophageal squamous cell carcinoma: does delayed surgery impact outcome?

BACKGROUND: Although esophagectomy traditionally is recommended to perform within 8 weeks after neoadjuvant chemoradiotherapy (nCRT), data from neoadjuvantly treated rectal cancer patients demonstrate that delayed surgery ([8 weeks) can maximize the effect of CRT. Despite these promising data, investigators are concerned that delayed surgery may lead to tumor repopulation. We report the impact of delayed surgery in patients with esophageal cancer who were treated with nCRT. METHODS: We retrospectively studied 276 esophageal cancer patients treated with nCRT and surgery between 2002 and 2008. We compared perioperative complication, rate of pathological complete response (pCR), distribution of tumor regression grade (TRG), and overall survival (OS) in patients who underwent surgery within 8 weeks (group A) and after 8 weeks (group B) after nCRT. RESULTS: There were 138 patients in each group with similar pre/post-nCRT characteristics. Delayed surgery did not result in lower surgical risk or higher pCR rate. Survival outcome also did not improve following a longer surgery interval (5-year OS: group A vs. group B, 29 vs. 23 %; P = 0.3). On the contrary, a subgroup analysis showed that delayed surgery might be hazardous, especially in patients who demonstrate a good response after nCRT. The amount of residual cancer, as measured by TRG, increased significantly after a longer surgical interval (P = 0.024). Survival also decreased after a longer surgical interval (5-year OS B8 vs. [8 weeks, 50 vs. 35 %; P = 0.038). CONCLUSIONS: After nCRT, esophagectomy should be performed within 8 weeks, especially in patients with good response.

Correction of left ventricular wall thickening from short-axis cine MRI for basal-descent through-plane motion.

PURPOSE: To solve the problem of the basal descent movement in quantification of the regional left ventricular (LV) myocardial wall thickness (WTh) and wall thickening (%WT) in short-axis (SA) cine MRI for effectively assessing the regional wall motion of LV myocardium. MATERIALS AND METHODS: LV long-axis tagged MRI and SA cine MRI were performed to calculate the longitudinal translation and circumferential WTh of LV myocardium in eight normal volunteers. The new SA end-systolic thickness (EST) data were reconstructed from the original EST data, based on the quantified longitudinal translation of LV myocardium. RESULTS: The mean %WT of six segments in the basal section after correction was significantly different from that before correction in both intra- and inter-operator experiments. The polar map also showed the significant improvement of the variability of regional %WT and lack of quantification of %WT in the most basal SA slices after correction. CONCLUSION: The proposed technique demonstrated an important advantage to calculate the %WT in the most basal SA myocardial tissue, which was considered difficult to be achieved using cine MRI.