The "Hitch-Stitch" for Preventing High Tracheal Stent Migration: Expanding Indications and Extended Experience.

BACKGROUND: Airway stenting is a standard treatment option for tracheo-bronchial obstruction and other conditions like tracheo-esophageal fistula (TEF). METHODS: To prevent stent migration, a percutaneous fixation strategy called the "hitch-stitch" was described in 2016 as an efficient technique. We describe an extended experience of the "hitch-stitch" for silicone stents in high tracheal stenting situations and expanding indications to metal stents. RESULTS: Seventy-four percutaneous stitches were placed in 54 patients (36 males and 18 females). The mean age of the patients was 42 (±19) years. The indication for stenting was tracheal stenosis in 63/74 (85%) cases and TEF in 11/74 (15%) cases. Silicone stents were used in 56/74 (75.5%) cases while self-expanding metal stents (SEMS) were used in 18/74 (24.5%) cases. The majority of the stents (62/74, 85%) were high tracheal stents. The "hitch-stitch" as an anti-migration strategy had a high success rate, with distal stent migration in only 2 cases (2.7%) as the stitch had given way-these were repositioned and hitched with double stitches. Minor complications included delayed skin healing (2.8%) and suture site infection (1.4%), which was successfully managed with oral antibiotics. Stitch removal was easy with no complications. CONCLUSION: In this large series of percutaneous "hitch-stitch" as a stent migration prevention strategy, long-term data shows it is safe and effective in an expanded cohort of silicone stents. Its extended utility is the successful application to metal stents, especially in TEF, where the consequences can be deleterious. It is simple to do, with minimal extra requirements and not associated with any significant complications.

A customized multimodality approach for prolonged air leaks (PAL) in mechanically ventilated patients.

ARDS in general and severe COVID ARDS (CARDS) is particularly associated with high rates of barotrauma. Two cases with severe CARDS developed bilateral pneumothorax with persistent air leak (PAL). Conservative management with prolonged chest tube drainage did not help in PAL resolution and both patients continued to be on high-end ventilatory support. The course was further complicated by the presence of septic shock. The 1st patient was taken up for a challenging procedure after spending 23 days on the mechanical ventilator. Diagnostic pleuroscopy revealed left-sided bullae and a surgical staple bullectomy was done. The right side showed a large bronchopleural fistula (BPF) on pleuroscopy, which was occluded using a customized endobronchial silicone blocker (CESB, described in 2018). This led to the reduction and finally, resolution of the bilateral PAL with subsequent removal of chest drains and weaning off the ventilator and oxygen. The second patient was managed with 2 CESB devices for occlusion of RUL anterior and posterior segment fistulae, followed by chest drain removal. These cases highlight effective out-of-the-box multimodality treatment using a combination of interventional pulmonary techniques and surgical stapling for a life-threatening bilateral PAL secondary to CARDS.

Lower respiratory tract sampling in COVID-19 acute respiratory distress syndrome: A focus on microbiology, cellular morphology, cytology, and management impact.

Background: Lower respiratory tract (LRT) sampling through bronchoscopy has been done sparingly in COVID-19 acute respiratory distress syndrome (ARDS) due to the high aerosol risk for the health-care workers (HCWs). Valuable information can be gained by a detailed evaluation of bronchoscopic LRT samples. Methods: LRT samples were obtained by bedside bronchoscopy severe COVID-19 ARDS patients on mechanical ventilation. Microbiological, cellular, and cytological studies including LRT COVID-19 reverse transcription-polymerase chain reaction were analyzed. Results: A total of 100 samples were collected from 63 patients, 53 were males (84%). Forty-three patients (68%) had at least 1 comorbidity. 55% of cases had a secondary bacterial infection, commonly with multidrug-resistant organisms (94.5%). The most common organisms were Klebsiella pneumoniae and Acinetobacter baumannii in 56.3% and 14.5% of cases, respectively. Fungal superinfection was observed in 9 patients (14.3%). Bronchoscopy helped confirm COVID-19 diagnosis in 1 patient and helped rule out COVID-19 in 3 patients. The median bronchoalveolar lavage fluid (BALF) white blood cell (WBC) count was 953 (inter quartile range; 400-2717), with mean neutrophil count 85.2% (±13.9) and mean lymphocyte count 14.8% (±13.9). Repeat sampling done in some patients showed a progressive increase in the total WBC count in BALF, an increase in neutrophil percentage, and a higher chance of isolating an organism on the culture. Rate of superinfection increased with a longer duration of illness. Bronchoscopic LRT sampling contributed significantly to modifying antibiotic coverage and discontinuing steroids in 37% of cases. Conclusions: Our study provides a detailed analysis of bronchoscopic LRT sampling in critically ill COVID-19 patients, augmenting disease understanding and contributing to clinical management.

Critical COVID-19-associated pulmonary mucormycosis: The underreported life-threatening spectrum of the mucormycosis epidemic.

The explosive rise in angioinvasive mucormycosis (MM) in India and other parts of the world has been described as the "epidemic following the COVID-19 pandemic," with the majority being rhino-orbital-cerebral MM. We report a case series of five COVID-19-associated pulmonary MM (CAPM) with an aggressive clinical course. Clinical and radiological clues were limited, and the initial suspicion of CAPM was the morphological appearance on bronchoscopy, which led to the diagnosis. Histopathology was consistently positive in all cases, while other microbiological and molecular tests had varying sensitivity. Most patients had a fulminant and fatal course. Also noted was dual fungal infection in 3/5 cases with coexisting multidrug resistant bacterial infection in all cases. CAPM is the hidden part of the COVID-MM epidemic and warrants a high degree of suspicion with early diagnosis and treatment.

A shorter symptom onset to remdesivir treatment (SORT) interval is associated with a lower mortality in moderate-to-severe COVID-19: A real-world analysis.

OBJECTIVES: Remdesivir is the current recommended anti-viral treatment in moderate-to-severe COVID-19. However, data on impact of timing of therapy, efficacy, and safety are limited. We evaluated the impact of timing of remdesivir initiation (symptom onset to remdesivir treatment [SORT] interval) on in-hospital all-cause mortality in patients with moderate-to-severe COVID-19. METHODS: This retrospective study was conducted between June 25 and October 3, 2020, at a tertiary care dedicated COVID center in India. Patients with moderate-to-severe COVID-19 (moderate: SpO2 <94%; severe: SpO2 <90%) were included. The main outcome was impact of SORT interval on in-hospital all-cause mortality. Subgroups were formed and analyzed based on SORT interval. RESULTS: Of 350 patients treated with remdesivir, 346 were included in the final analysis. Overall, 76 (22.0%) patients died (moderate: 3 [2.8%], severe: 73 [30.8%]). All-cause mortality was significantly lower in patients with SORT interval ≤9 days (n = 260) vs SORT interval >9 days (n = 86; 18.1% vs 33.7%; p = 0.004). The odds of death were significantly lower in patients with SORT interval ≤9 days vs >9 days (odds ratio = 0.43; 95% CI, 0.25-0.75; p = 0.003). CONCLUSION: Remdesivir initiation ≤9 days from symptom onset was associated with mortality benefit, defining a treatment window and reinforcing the need for appropriately-timed remdesivir in moderate-to-severe COVID-19.

Use of fibrinolytics and deoxyribonuclease in adult patients with pleural empyema: a consensus statement.

Although our understanding of the pathogenesis of empyema has grown tremendously over the past few decades, questions still remain on how to optimally manage this condition. It has been almost a decade since the publication of the MIST2 trial, but there is still an extensive debate on the appropriate use of intrapleural fibrinolytic and deoxyribonuclease therapy in patients with empyema. Given the scarcity of overall guidance on this subject, we convened an international group of 22 experts from 20 institutions across five countries with experience and expertise in managing adult patients with empyema. We did a literature and internet search for reports addressing 11 clinically relevant questions pertaining to the use of intrapleural fibrinolytic and deoxyribonuclease therapy in adult patients with bacterial empyema. This Position Paper, consisting of seven graded and four ungraded recommendations, was formulated by a systematic and rigorous process involving the evaluation of published evidence, augmented with provider experience when necessary. Panel members participated in the development of the final recommendations using the modified Delphi technique. Our Position Paper aims to address the existing gap in knowledge and to provide consensus-based recommendations to offer guidance in clinical decision making when considering the use of intrapleural therapy in adult patients with bacterial empyema.

Use of an Extended Working Channel in High-Risk Transbronchial Biopsy: An Innovative Use of an Existing Modality to Minimize Bleeding and Hypoxia.

OBJECTIVE: Bleeding is one of the main complications of transbronchial lung biopsy (TBBx) more so with conditions such as azotaemia and coagulopathy. Baseline hypoxia worsens the consequences of TBBx bleeding and can lead to escalation of care. In our experience, TBBx performed through a guide sheath (GS) using it as an extended working channel (EWC) helps minimize bleeding risk. We hypothesized that the EWC produces a tamponade effect in the close vicinity of the biopsy site, both reducing bleeding risk and restricting bleeding to a smaller segment. In this study, we assessed the impact of an additional EWC in high-risk (HR) patients undergoing TBBx, to reduce bleeding and enhance safety. METHODS: Retrospective study between January 2014 and December 2018 looking at the risk of bleeding following TBBx performed through a GS (EWC) in patients at high risk for bleeding-related complications. Bleeding incidence and consequent hypoxic events requiring escalation of care were noted. The specimen diagnostic yield was also analyzed. SPSS statistics were used-data are reported as mean and standard deviation for continuous variables, and number and percentage for discrete variables. RESULTS: Eight hundred four TBBxs were performed during the study period, and 105 (13.1%) procedures were done in the HR individuals using a GS as an EWC. No significant bleeding requiring escalation of care was seen with the use of EWC-GS. Histopathology revealed adequate sampling in all cases. CONCLUSIONS: A GS as an EWC was used to reduce the bleeding risk, consequent hypoxia, and prevent escalation of care in TBBx in HR patients. Adequate tissue was obtained without any complications. Though prospective, randomized, multicenter trials using an EWC in HR-TBBx are important, they are challenging to do due to the HR population under study.

A Novel Technique for the Management of Massive Hemoptysis: The Customized Endobronchial Silicone Blocker.

OBJECTIVE: Massive hemoptysis (MH) has a high mortality rate. Therapeutic options include bronchoscopy for endobronchial lesions, bronchial artery embolization (BAE), and emergency surgery. Scant options exist for patients who are not candidates for these modalities. Culprit bronchial segment occlusion is an option to prevent "spillover flooding → hypoxia." Applying this concept, we describe a case series of MH control using a novel bronchoscopically inserted customized endobronchial silicone blocker (CESB). We analyzed the safety and efficacy of CESBs in a select subset of patients with MH. METHODS: Inclusion criteria were patients with MH who were unstable for surgery/BAE, failed BAE, or relatively contraindicated/refused BAE. CESBs were manufactured on-site by modifying silicone stents, inserted using rigid bronchoscopy and reinforced with glue. The CESB was removed after 6 weeks when possible. A successful outcome was defined as immediate bleeding control with no recurrence after removal. RESULTS: Over 4.5 years, 13 episodes of MH in 12 patients meeting the criteria specified earlier were treated with CESBs. Seven of 12 patients had tuberculosis, 4 active and 3 inactive. One patient had mucormycosis, 1 post-lobectomy, 1 endobronchial renal cell carcinoma, 1 fibrosing mediastinitis, and 1 patient had metastatic laryngeal Ca. Eight of 12 patients were taken for primary-CESB placement. Four of 12 patients were sent for BAE, which was unsuccessful, and rescue-CESB was done for definitive management. The success rate, as defined earlier, was 92.3%, with no deaths from MH. CONCLUSIONS: Innovative bronchoscopically inserted CESBs are an effective strategy in MH when patients are unstable or fail conventional management.

Bronchial thermoplasty for severe asthma: A position statement of the Indian chest society.

Bronchial thermoplasty (BT) is an interventional bronchoscopic treatment for severe asthma. There is a need to define patient selection criteria to guide clinicians in offering the appropriate treatment options to patients with severe asthma. METHODOLOGY: An expert group formed this statement under the aegis of the Indian Chest Society. We performed a systematic search of the MEDLINE and EMBASE databases to extract evidence on patient selection and the technical performance of BT. RESULTS: The experts agreed that the appropriate selection of patients is crucial and proposed identification of the asthma phenotype, a screening algorithm, and inclusion/exclusion criteria for BT. In the presence of atypical clinical or chest radiograph features, there should be a low threshold for obtaining a thoracic computed tomography scan before BT. The patient should not have had an asthma exacerbation in the preceding two weeks from the day of the procedure. A 5-day course of glucocorticoid should be administered, beginning three days before the procedure day, and continued until the day following the procedure. General Anesthesia (total intravenous anesthesia with a neuromuscular blocker) provides ideal conditions for performing BT. A thin bronchoscope with a 2.0 mm working channel is preferable. An attempt should be made to deliver the maximum radiofrequency activations. Middle lobe treatment is not recommended. Following the procedure, overnight observation in the hospital, and a follow-up visit, a week following each treatment session, is desirable. CONCLUSION: This position statement provides practical guidance regarding patient selection and the technical performance of BT for severe asthma.

Endobronchial ultrasound-guided mediastinal lymph node forceps biopsy in patients with negative rapid-on-site-evaluation: A new step in the diagnostic algorithm.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) provides a high diagnostic yield in lung cancer, but the yield for benign conditions and lymphoma is lower. The material obtained by EBUS-TBNA is limited by the lack of histopathological samples in some cases. The current 'expanded' aims of mediastinal lymph node (MLN) sampling are both an accurate diagnosis and adequate material for 'targeted' processing in malignant and benign disease. The sample obtained with the 21/22G EBUS needle may not be sufficient in all situations. OBJECTIVES: The aim of the study was to evaluate the role of a novel technique for EBUS-guided MLN forceps biopsy (EBUS-TBFB) when EBUS-TBNA with rapid on-site-evaluation (ROSE) failed to provide a diagnosis. In addition, the technical aspects and safety of EBUS-TBFB were studied. METHODS: About 30 consecutive patients with enlarged MLN, with a negative EBUS-TBNA ROSE were included. EBUS-TBFB was done by the method described below. The histopathology and complications were recorded. RESULTS: Adequate samples for analysis were obtained in all the patients with both EBUS-TBNA and EBUS-TBFB. In patients with a non-diagnostic EBUS-ROSE, EBUS-TBFB led to positive diagnostic results in an additional 8/30 patients (27%). Mild bleeding was noted in two patients who underwent EBUS-TBFB, which resolved with conservative management. The procedure was safe with no major complications. CONCLUSION: In patients with a negative EBUS-ROSE, EBUS-TBFB using this technique is safe and augments the diagnostic yield. EBUS-TBFB adds to the armamentarium of EBUS, especially in benign aetiologies of MLN enlargement.

Cooperative adaptation to therapy (CAT) confers resistance in heterogeneous non-small cell lung cancer.

Understanding intrinsic and acquired resistance is crucial to overcoming cancer chemotherapy failure. While it is well-established that intratumor, subclonal genetic and phenotypic heterogeneity significantly contribute to resistance, it is not fully understood how tumor sub-clones interact with each other to withstand therapy pressure. Here, we report a previously unrecognized behavior in heterogeneous tumors: cooperative adaptation to therapy (CAT), in which cancer cells induce co-resistant phenotypes in neighboring cancer cells when exposed to cancer therapy. Using a CRISPR/Cas9 toolkit we engineered phenotypically diverse non-small cell lung cancer (NSCLC) cells by conferring mutations in Dicer1, a type III cytoplasmic endoribonuclease involved in small non-coding RNA genesis. We monitored three-dimensional growth dynamics of fluorescently-labeled mutant and/or wild-type cells individually or in co-culture using a substrate-free NanoCulture system under unstimulated or drug pressure conditions. By integrating mathematical modeling with flow cytometry, we characterized the growth patterns of mono- and co-cultures using a mathematical model of intra- and interspecies competition. Leveraging the flow cytometry data, we estimated the model's parameters to reveal that the combination of WT and mutants in co-cultures allowed for beneficial growth in previously drug sensitive cells despite drug pressure via induction of cell state transitions described by a cooperative game theoretic change in the fitness values. Finally, we used an ex vivo human tumor model that predicts clinical response through drug sensitivity analyses and determined that cellular and morphologic heterogeneity correlates to prognostic failure of multiple clinically-approved and off-label drugs in individual NSCLC patient samples. Together, these findings present a new paradox in drug resistance implicating non-genetic cooperation among tumor cells to thwart drug pressure, suggesting that profiling for druggable targets (i.e. mutations) alone may be insufficient to assign effective therapy.

Airway Stenosis Related to Foreign Body Aspiration: An Under-recognized Long term Complication.

INTRODUCTION: Sequelae of chronic foreign body aspiration include occlusive granulation tissue formation, which can cause delayed fixed airway stenosis. The aim of this study is to highlight this complication, which should be diagnosed early and treated proactively. METHODS: We present a case series of areca nut aspiration, an organic foreign body commonly chewed in Southeast Asia, complicated by delayed airway stenosis and examine the peculiar nature of areca nut that predisposes to this complication. RESULTS: Long-term sequelae of areca nut aspiration are granulation tissue formation, potentially complicated by airway stenosis due to the mechanical and chemical irritant nature of areca nut. DISCUSSION: Organic impacted foreign bodies such as areca nut can cause delayed complications of airway stenosis. Both the sharp edges of the areca nut and chemical irritation caused by alkaloids released by the nut in constant contact with the airway mucosa can predispose to this long-term complication. Early diagnosis and appropriate therapeutic interventions such as balloon bronchoplasty can help restore airway patency and prevent lung damage.

A Multicenter Study on the Utility of EBUS-TBNA and EUS-B-FNA in the Diagnosis of Mediastinal Lymphoma.

BACKGROUND: There is conflicting data on the utility of endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) for the detection and subtyping of lymphomas. Herein, we present our experience with EBUS-TBNA in suspected lymphoma. METHODS: This was a multicenter retrospective study of subjects with suspected lymphoma who underwent EBUS-TBNA (July 2011 to June 2017). The performance characteristics of EBUS-TBNA were calculated separately for suspected new-onset and recurrent lymphoma as well as for subtyping. We also analyzed the factors predicting the yield of EBUS-TBNA in suspected lymphoma. RESULTS: Among the 4803 EBUS procedures performed, 92 (1.9%) subjects had either suspected or proven lymphoma; 48 were finally diagnosed to have lymphoma. The diagnostic sensitivities of EBUS-TBNA in new-onset and recurrent lymphomas were 72.7% and 73.3%, respectively. Only 24.2% (8/33) subjects with new-onset lymphoma could be appropriately subtyped. This low yield was possibly due to inadequate material for cell block in 10 subjects, and performance of immunophenotyping and flow cytometry in only 5 and 1 subjects, respectively. Among the suspected cases of recurrence, EBUS-TBNA was sufficient for management in 81.8% (18/22). On a multivariate analysis, no factor (rapid onsite evaluation, needle size, number of lymph nodes sampled, passes per node, and size of the largest lymph node sampled) predicted the diagnostic yield. CONCLUSION: EBUS-TBNA is a useful investigation in the diagnostic algorithm of suspected lymphoma as it helps avoid other invasive diagnostic procedures. The sensitivity of EBUS-TBNA in subtyping new-onset mediastinal lymphoma depends on the adequacy of cell aspirate and the judicious utilization of pathologic techniques.

Flexible bronchoscopy-guided vocal cord biopsy under conscious sedation: An option to surgical biopsy in special situations.

INTRODUCTION: Vocal cord (VC) biopsies are usually performed with rigid laryngoscopy under general anesthesia (GA). In patients with comorbidities such as cardiovascular or pulmonary disease, the risk of GA is high, with morbidity and potential mortality. We describe VC biopsy (VCB) in such a high-risk cohort, done safely and successfully with flexible bronchoscopy-VCB (FB-VCB) and conscious sedation. METHODS: FB-VCB was done in two groups of patients - the first at high risk for GA due to comorbidities and the second group where VC lesions were found incidentally in the course of FB done for other reasons. FB was done with local anesthesia and conscious sedation, and the VC lesion was identified. Flexible forceps were introduced through the working channel of the bronchoscope, and the lesions were carefully sampled. RESULTS: FB-VCB was performed in 15 patients (14 males and 1 female) with a mean age of 60.7 ± 12.1 years. Of these 15 patients, 6 patients were poor candidates for GA due to comorbidities and 9 patients had incidental VC lesions found during bronchoscopy. A diagnosis was made in 14/15 (93.3%) patients. Complications included a mild ooze and hoarseness of voice for a few days, which did not require any intervention. CONCLUSION: We report one of the few series of patients with VC biopsies done with FB (FB-VCB) under conscious sedation, without significant complications. It is safe and useful in high-risk patients who are poor candidates for GA, with a good diagnostic yield.

Utility of EBUS-TBNA in PET-positive mediastinal lymph nodes in subjects with extra-thoracic malignancy.

BACKGROUND/AIM: Patients with primary extra-thoracic malignancy (ETM) often have hyper-metabolic mediastinal lymph nodes (HM-MLN) in the PET-scan done for initial staging or post treatment follow-up. There is scant data on the etiology of HM-MLN in such patients, which can also be due to non-malignant causes. We used endobronchial ultrasound (EBUS) guided sampling to determine the etiology of HM-MLN in patients with ETM and study the relationship between PET-SUV values and a diagnosis of malignancy in this population. MATERIALS AND METHODS: 65 consecutive patients, from March 2013 to March 2017 with either known ETM for primary staging or post-treatment follow-up, with PET CT showing HM-MLN (SUV > 2.5) were included in the study. RESULTS: 65 patients with ETM had EBUS-TBNA for HM-MLN. 20/65 (30.7%) were malignant, 45/65 (69.23%) were benign MLN. In patients with benign etiology of HM-MLN, 6/45 (13.3%) had necrotising granulomatous, 24/45 (53.3%) had non- necrotising granulomatous MLN and 15/45 (33.3%) had reactive MLN. We found discordance (i.e. primary ETM responded to treatment and a new HM-MLN was detected) in 21/65 (32.3%) patients with PET-CT done for initial ETM staging, and 44/65 (67.7%) with a post-treatment PET-CT. showed. Correlating SUV with diagnoses, the SUV values in EBUS-proven malignant MLN were 8.9 ± 4.1, while they were 10.2 ± 5.57 in benign MLN. There was no statistically significant difference between the SUV of benign and malignant MLNs. CONCLUSION: This study shows a significant incidence of EBUS-TBNA proven benign diagnoses 45/65 (69.2%) in 'SUV-deemed-malignant MLN' and a poor relationship between high SUV and malignant MLN, in patients with known ETM. The ETM related HM-MLN have a significant chance of being benign, and a tissue diagnosis is imperative as it impacts on the treatment plan and prognosis.

Bronchoscopic lung cryobiopsy: An Indian association for bronchology position statement.

BACKGROUND: Bronchoscopic lung cryobiopsy (BLC) is a novel technique for obtaining lung tissue for the diagnosis of diffuse parenchymal lung diseases. The procedure is performed using several different variations of technique, resulting in an inconsistent diagnostic yield and a variable risk of complications. There is an unmet need for standardization of the technical aspects of BLC. METHODOLOGY: This is a position statement framed by a group comprising experts from the fields of pulmonary medicine, thoracic surgery, pathology, and radiology under the aegis of the Indian Association for Bronchology. Sixteen questions on various technical aspects of BLC were framed. A literature search was conducted using PubMed and EMBASE databases. The expert group discussed the available evidence relevant to each question through e-mail and a face-to-face meeting, and arrived at a consensus. RESULTS: The experts agreed that patients should be carefully selected for BLC after weighing the risks and benefits of the procedure. Where appropriate, consideration should be given to perform alternate procedures such as conventional transbronchial biopsy or subject the patient directly to a surgical lung biopsy. The procedure is best performed after placement of an artificial airway under sedation/general anesthesia. Fluoroscopic guidance and occlusion balloon should be utilized for positioning the cryoprobe to reduce the risk of pneumothorax and bleeding, respectively. At least four tissue specimens (with at least two of adequate size, i.e., ≥5 mm) should be obtained during the procedure from different lobes or different segments of a lobe. The histopathological findings of BLC should be interpreted by an experienced pulmonary pathologist. The final diagnosis should be made after a multidisciplinary discussion. Finally, there is a need for structured training for performing BLC. CONCLUSION: This position statement is an attempt to provide practical recommendations for the performance of BLC in DPLDs.