Specific human leucocyte antigen-DQ risk epitope mismatches are associated with chronic lung allograft dysfunction after lung transplantation.

A high-risk epitope mismatch (REM) (found in DQA1∗05 + DQB1∗02/DQB1∗03:01) is associated with de novo donor specific antibodies after lung transplantation (LTx). Chronic lung allograft dysfunction (CLAD) remains a barrier to LTx survival. This study aimed to measure the association between DQ REM and the risk of CLAD and death after LTx. A retrospective analysis of LTx recipients at a single center was conducted between January 2014 and April 2019. Molecular typing at human leucocyte antigen-DQA/DQB identified DQ REM. Multivariable competing risk and Cox regression models were used to measure the association between DQ REM, time-to-CLAD, and time-to-death. DQ REM was detected in 96/268 (35.8%), and DQ REM de novo donor specific antibodies were detected in 34/96 (35.4%). CLAD occurred in 78 (29.1%), and 98 (36.6%) recipients died during follow-up. When analyzed as a baseline predictor, DQ REM status was associated with CLAD (subdistribution hazard ratio (SHR), 2.19; 95% confidence interval [CI], 1.40-3.43; P = .001). After adjustment for time-dependent variables, DQ REM dn-DSA (SHR, 2.43; 95% CI, 1.10-5.38; P = .029) and A-grade rejection score (SHR, 1.22; 95% CI, 1.11-1.35; P = <.001), DQ REM status was not independently associated with CLAD. DQ REM was not associated with death (hazard ratio, 1.18; 95% CI, 0.72-1.93; P = .51). Classification of DQ REM may identify patients at risk of poor outcomes and should be incorporated into clinical decision-making.

Whole lung lavage: Treating pulmonary alveolar proteinosis at the time of COVID pandemic.

Pulmonary alveolar proteinosis (PAP) is a rare syndrome due to increased production or decreased clearance of surfactant in alveoli and terminal bronchi that cause hypoxemic respiratory insufficiency. Here we present a patient with PAP whose disease was exacerbated by superimposed COVID-19 pneumonia. He underwent whole lung lavage (WLL). Evaluation of the viral count of the first and the last lavage of the left lung showed viral load in the alveolar space dropped by approximately 10-folds, however the magnitude of the viral load was substantial in both lavage samples. Whole pulmonary lavage may be used as a treatment option on patients with PAP even when the disease is exacerbated by COVID-19 pneumonia.

Study of Alteplase for Respiratory Failure in SARS-CoV-2 COVID-19: A Vanguard Multicenter, Rapidly Adaptive, Pragmatic, Randomized Controlled Trial.

BACKGROUND: Pulmonary vascular microthrombi are a proposed mechanism of COVID-19 respiratory failure. We hypothesized that early administration of tissue plasminogen activator (tPA) followed by therapeutic heparin would improve pulmonary function in these patients. RESEARCH QUESTION: Does tPA improve pulmonary function in severe COVID-19 respiratory failure, and is it safe? STUDY DESIGN AND METHODS: Adults with COVID-19-induced respiratory failure were randomized from May14, 2020 through March 3, 2021, in two phases. Phase 1 (n = 36) comprised a control group (standard-of-care treatment) vs a tPA bolus (50-mg tPA IV bolus followed by 7 days of heparin; goal activated partial thromboplastin time [aPTT], 60-80 s) group. Phase 2 (n = 14) comprised a control group vs a tPA drip (50-mg tPA IV bolus, followed by tPA drip 2 mg/h plus heparin 500 units/h over 24 h, then heparin to maintain aPTT of 60-80 s for 7 days) group. Patients were excluded from enrollment if they had not undergone a neurologic examination or cross-sectional brain imaging within the previous 4.5 h to rule out stroke and potential for hemorrhagic conversion. The primary outcome was Pao2 to Fio2 ratio improvement from baseline at 48 h after randomization. Secondary outcomes included Pao2 to Fio2 ratio improvement of > 50% or Pao2 to Fio2 ratio of ≥ 200 at 48 h (composite outcome), ventilator-free days (VFD), and mortality. RESULTS: Fifty patients were randomized: 17 in the control group and 19 in the tPA bolus group in phase 1 and eight in the control group and six in the tPA drip group in phase 2. No severe bleeding events occurred. In the tPA bolus group, the Pao2 to Fio2 ratio values were significantly (P < .017) higher than baseline at 6 through 168 h after randomization; the control group showed no significant improvements. Among patients receiving a tPA bolus, the percent change of Pao2 to Fio2 ratio at 48 h (16.9% control [interquartile range (IQR), -8.3% to 36.8%] vs 29.8% tPA bolus [IQR, 4.5%-88.7%]; P = .11), the composite outcome (11.8% vs 47.4%; P = .03), VFD (0.0 [IQR, 0.0-9.0] vs 12.0 [IQR, 0.0-19.0]; P = .11), and in-hospital mortality (41.2% vs 21.1%; P = .19) did not reach statistically significant differences when compared with those of control participants. The patients who received a tPA drip did not experience benefit. INTERPRETATION: The combination of tPA bolus plus heparin is safe in severe COVID-19 respiratory failure. A phase 3 study is warranted given the improvements in oxygenation and promising observations in VFD and mortality. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04357730; URL: www. CLINICALTRIALS: gov.

Cannon ball appearance on radiology in a middle-aged diabetic female.

Pulmonary tuberculosis is commonly presented as cavitary lesion and infiltrations. It commonly involves upper lobe. Lower lobe involvement is less common. Various atypical presentations of tuberculosis on radiology are reported like mass, solitary nodule, multi lober involvement including lower lobes. Atypical presentations are more commo in patients with immunocompromised conditions like Diabetes Mellitus, anemia, renal failure, liver diseases, HIV infection, malignancy, patients on immunosuppressive therapy. Cannon ball presentation of pulmonary tuberculosis is extremely rare and not so common. Common causes of cannon ball presentation in lung are metastasis, fungal infections, Wegener's grannulomatosis, sarcoidosis, etc. We report here a case of middle year female with diabetes mellitus presented with atypical symptoms with cannon ball appearance on radiology and found to be of tuberculosis in origin. Thus any patients with immunocompromised condition can present with atypical manifestation of tuberculosis either clinically or radiologicaly in high endemic countries for tuberculosis.

Spontaneous pneumomediastinum: time for consensus.

Pneumomediastinum (PM) is defined as the presence of free air in the mediastinal cavity. It is often regarded as a revealing sign of a more serious medical condition. PM is broken down into two categories, one, with an instigating event, referred to as secondary PM. The other is when free air is discovered in the mediastinal cavity without a clear etiology, referred to as spontaneous pneumomediastinum (SPM). Often misdiagnosed due to the vague nature of presenting symptoms, SPM must be part of the differential diagnosis of a chest pain patient to expedite discovery and if necessary, management. A MedLine/PubMED search was performed identifying all relevant articles with "SPM" in the title. Six case series were reviewed to determine what clinical scenario constitutes a possible case of SPM. Results showed that almost all patients with SPM exhibited some chest pain, but Hamman's crunch was present in only one-fifth of patients. Patients with certain pre-existing pulmonary diseases showed a greater propensity for the presence of free air in the mediastinal cavity. SPM must be diagnosed and managed promptly due to rare, but serious complications and any chest pain with an unknown etiology should contain SPM in the differential diagnosis.

Manifestations of pulmonary disease in adults with congenital heart disease.

Children with congenital heart disease (CHD) are more frequently living into adulthood as their survival has improved due to availability of better medical and surgical management in recent times. Management of adults with CHD is emerging as new challenge in the field of medical science. Adults surviving with CHD for longer duration have been observed to develop more complications as compared to children. It is important to recognise and treat these complications early to reduce the morbidity. Pulmonary diseases are the most common systemic complications associated with adults having CHD. These individuals are presenting to clinics or emergency for pulmonary complaints, hence, pulmonologist must be aware about the pulmonary manifestations of CHD and their management.

A 65-year-old female with an endobronchial mass lesion.

Glomus tumor is a rare, predominantly benign, soft tissue tumor. The lower respiratory tract is an uncommon site of origin of glomus tumor, so endobronchial glomus tumor is extremely rare. Such tumors are mostly benign and identified incidentally on imaging. Diagnosis is confirmed by immunohistochemical staining, and resection is the treatment of choice. We report a middle-age female with endobronchial glomus tumor. This is 23rd case of reported pulmonary glomus tumor, to the best of our knowledge.

Elongated uvula and diagnostic utility of spirometry in upper airway obstruction.

Elongated uvula is relatively an uncommon condition. Upper airway obstruction is often a missed complication of such a rare condition. Clinical presentations of upper airway obstruction often mimic asthma. Hence it is very easily mis-diagnosed as asthma. Spirometry offers a very simple test to diagnose upper airway obstruction very early and easily. Once diagnosed, the management of elongated uvula, almost exclusively, is surgical excision leading to total cure. Here is a case report of such a rare condition.

Pulmonary actinomycosis in fine needle aspiration cytology.

Pulmonary actinomycosis is a rare bacterial lung disease caused by one of two types of bacteria, Actinomyces or Propioni. Pulmonary actinomycosis in the lung causes lung cavities, lung nodules, and pleural effusion. We report here a case of pulmonary actinomycosis that was diagnosed by fine needle aspiration cytology (FNAC). A 45 year-old male with a history of smoking and alcohol abuse, presented with complaints of cough with hemoptysis, right-sided chest pain, and fever of two months' duration. A chest radiograph and computed tomography (CT) of the thorax showed a right upper lobe mass lesion with hilar lymphadenopathy. CT-guided FNAC revealed colonies of Actinomyces surrounded by polymorphs. The disease is commonly confused with other chronic suppurative lung diseases and malignancy. An early diagnosis by FNAC prevents difficulties in the management of the disease, as well as considerable physiological and physical morbidity, including unwarranted surgery.