Hydatid cyst in heart and lung: a rare case with a 5-year follow-up.

This report describes a male in his late 20s who presented with a 2-month history of recurrent haemoptysis and chest pain. A chronic infection, such as tuberculosis, was suspected. He had undergone surgical resection of an intrapericardial hydatid cyst in the past. His blood investigations showed peripheral eosinophilia, and his chest X-ray showed a cystic oval lesion in the left upper zone. A CT pulmonary angiogram revealed filling defects in the bilateral segmental and subsegmental arteries with a cystic lesion in the left upper lobe. Further workup, including bronchoalveolar lavage culture and MRI of the thorax, confirmed the diagnosis of a hydatid cyst of pulmonary echinococcosis. This case illustrates the presentation of multisystemic echinococcosis in a young male with no other risk factors, initially treated with surgical resection and antihelminthic therapy. The disease later recurred, which required prolonged medications, which brought the patient into remission.

Bronchial Dieulafoy's disease: A series of seven cases with review of the literature.

Bronchial Dieulafoy's disease (BDD), remains poorly understood, with only 88 cases reported globally. Herein, we present the largest case series (n = 7) from a single centre, between 2017 and 2023, retrospectively reviewed, detailing clinical presentations, diagnoses, management and up to 4-year follow-up outcomes. Diagnosis relied on characteristic lesions detected through white light bronchoscopy with or without endobronchial ultrasound (EBUS) or narrow band imaging (NBI), along with computed tomography (CT) scans or bronchial angiography. Identification of aberrant vessels beneath lesions and bronchoscopy details were documented. Treatment modalities and follow-up outcomes until December 2023 were noted. All patients were non-smokers. Review of imaging findings by an experienced radiologist was crucial in suspected cases due to risk of bleeding and often unconclusive results from biopsy. Management of BDD varied, with six patients undergoing bronchial artery embolization (BAE) and one requiring lobectomy; four patients received additional endobronchial therapy, one died due to malignancy, none experienced recurrence of haemoptysis. Identifying patients with large volume haemoptysis disproportionate to parenchymal disease in CT scans is important. A bronchoscopic surveillance is crucial to avoid biopsy; it can be confirmed using EBUS of NBI. While no established guidelines exist, BAE and endobronchial therapy emerge as valuable interventions, with surgical resection reserved for recurrent cases.

Pleural effusion guidelines from ICS and NCCP Section 1: Basic principles, laboratory tests and pleural procedures.

Pleural effusion is a common problem in our country, and most of these patients need invasive tests as they can't be evaluated by blood tests alone. The simplest of them is diagnostic pleural aspiration, and diagnostic techniques such as medical thoracoscopy are being performed more frequently than ever before. However, most physicians in India treat pleural effusion empirically, leading to delays in diagnosis, misdiagnosis and complications from wrong treatments. This situation must change, and the adoption of evidence-based protocols is urgently needed. Furthermore, the spectrum of pleural disease in India is different from that in the West, and yet Western guidelines and algorithms are used by Indian physicians. Therefore, India-specific consensus guidelines are needed. To fulfil this need, the Indian Chest Society and the National College of Chest Physicians; the premier societies for pulmonary physicians came together to create this National guideline. This document aims to provide evidence based recommendations on basic principles, initial assessment, diagnostic modalities and management of pleural effusions.

Clinical Characteristics and Outcomes of Interstitial Lung Disease in Primary Sjögren's Syndrome: A Retrospective Cohort Study.

Objectives: To describe the characteristics of primary Sjögren's syndrome (pSS) patients with interstitial lung disease (ILD) and to assess treatment response. Methods: All patients of pSS from 2010 to 2019 were retrospectively identified. Lung function tests, high resolution computed tomography (HRCT) findings, and treatment outcomes were analysed. Results: Out of 550 patients with pSS, ILD was detected in 33 patients (frequency of 6 %). The mean(±SD) age at the diagnosis of pSS was 50 (± 9.3) years. 28/33(84.8%) were females. ILD onset preceded pSS diagnosis in 2 (6%) patients, simultaneously diagnosed in 21 (63.6%) patients and developed after pSS onset in 10 (30.3%) patients. 5 patients (15.15 %) were asymptomatic for ILD. Non-specific interstitial pneumonia (NSIP) accounted for the most frequent ILD subtype, in 15 patients (45.5%). Mycophenolate mofetil (MMF) was the most frequently used steroid sparing agent, in 25 patients (75.7%). 7 patients were lost to follow up. Response was seen in 22 patients, whereas 3 patients were non responders. There was one mortality due to lower respiratory tract infection-related sepsis. Presence of sicca symptoms [91.5% vs 8.7% (p<0.001)], NSIP pattern of ILD [90% vs 10% (p = 0.002)], and absence of Raynaud's phenomenon [91.7% vs 8.3% (p<0.001)] were significantly associated with responder status when compared to non-responders. Conclusion: ILD in primary Sjögren's syndrome is not an uncommon entity, and immunosuppression with steroids along with steroid-sparing agents led to good clinical outcomes of ILD in a majority of the patients in our cohort.

Tracheobronchopathia Osteochondroplastica - to Biopsy or not to Biopsy? A Relook at The Rare Disease.

BACKGROUND: Tracheobronchopathia osteochondroplastica (TPO) is a rare idiopathic disease involving the tracheobronchial tree. It is mostly an incidental finding with non-specific clinical manifestations. It has typical bronchoscopic, radiological features and biopsy is usually considered non-essential. The study aimed to determine whether biopsy makes a difference in the management of patients. METHODS: All patients diagnosed with TPO in our institution over 15 years (2005 to 2020) were included in this study. Their medical records, chest computed tomography (CT), and bronchoscopy reports were retrospectively reviewed, and data were analysed. All the CT images were reviewed by a senior chest radiologist. RESULTS: From the 20,000 bronchoscopies and 260,000 CT thorax images obtained, 28 cases were diagnosed as TPO based on either bronchoscopy or radiology or both. Among the 19 cases diagnosed through bronchoscopy, 16 underwent a biopsy. In addition to TPO features, biopsy showed additional diagnoses in 6 cases. In 9 cases, TPO was not initially diagnosed by CT but by bronchoscopy. In 8 patients, TPO was diagnosed incidentally on CT performed for other reasons. On follow-up with the treatment of underlying/co-existing concomitant aetiologies, clinical improvement was noted in all patients. None of them progressed to respiratory failure or airway obstruction until the last follow-up. CONCLUSION: Among patients who underwent bronchoscopic biopsy of TPO lesions, 38% had biopsy results showing an alternative aetiology, which led to changes in the treatment plan for all these patients. Hence, a bronchoscopic biopsy of TPO lesions should be performed to rule out other aetiologies.

Fat emboli-Related diffuse alveolar haemorrhage (FEDAH) an acronym to remember-Case series.

Fat embolism syndrome (FES) is a rare but potentially fatal complication of trauma or orthopaedic surgery, which presents predominantly with pulmonary symptoms. The rapid worsening respiratory failure in a previously normal orthopaedic surgery or trauma patients usually get evaluated for pulmonary embolism, fat-embolism-related acute respiratory distress or transfusion related acute lung injury. Orthopaedic surgeons and clinicians need to be aware of related entity termed 'Fat Embolism related Diffuse Alveolar Haemorrhage' (FEDAH). The clinical presentation in an orthopaedic surgery of trauma patient with FEDAH are haemoptysis, worsening type 1 respiratory failure and oxygen requirement, drop in haemoglobin levels with chest x-ray/computed tomography suggestive of Diffuse alveolar haemorrhage (DAH). Early bronchoscopy and bronchoalveolar lavage (BAL) confirmation of DAH, presence of BAL haemosiderophages and lipid-laden macrophages are the pointers in the early diagnosis of FEDAH. It needs a high clinical suspicion and interdepartmental collaborative measures. Timely referral from orthopaedic surgeons, early bronchoscopy and treatment with steroids is key in diagnosis and management.

An overview on the principles of management of haemoptysis.

Haemoptysis is a frequently encountered presentation in thoracic surgery practice. Most of the patients present with chronic haemoptysis while 5% of them will present with life-threatening acute haemoptysis. Emergency surgery used to be the first-line management in acute life-threatening haemoptysis which resulted in significant morbidity and mortality. With advancements in interventional procedures, most of these acute presentations are now being managed conservatively by interventionists. In a country like India with a high incidence of tuberculosis and other infectious diseases of the lungs, haemoptysis is even more common. While interventional procedures help to tide over the crisis and earn valuable time to stabilise a haemorrhaging patient, surgical resection is the definitive management most of the time. This review will endeavour to establish the definition, aetiology, emergency, and definitive management of a patient who presents with haemoptysis.

Systemic corticosteroids for the treatment of COVID-19: Equity-related analyses and update on evidence.

BACKGROUND: Systemic corticosteroids are used to treat people with COVID-19 because they counter hyper-inflammation. Existing evidence syntheses suggest a slight benefit on mortality. Nonetheless, size of effect, optimal therapy regimen, and selection of patients who are likely to benefit most are factors that remain to be evaluated. OBJECTIVES: To assess whether and at which doses systemic corticosteroids are effective and safe in the treatment of people with COVID-19, to explore equity-related aspects in subgroup analyses, and to keep up to date with the evolving evidence base using a living systematic review approach. SEARCH METHODS: We searched the Cochrane COVID-19 Study Register (which includes PubMed, Embase, CENTRAL, ClinicalTrials.gov, WHO ICTRP, and medRxiv), Web of Science (Science Citation Index, Emerging Citation Index), and the WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies to 6 January 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that evaluated systemic corticosteroids for people with COVID-19. We included any type or dose of systemic corticosteroids and the following comparisons: systemic corticosteroids plus standard care versus standard care, different types, doses and timings (early versus late) of corticosteroids. We excluded corticosteroids in combination with other active substances versus standard care, topical or inhaled corticosteroids, and corticosteroids for long-COVID treatment. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. To assess the risk of bias in included studies, we used the Cochrane 'Risk of bias' 2 tool for RCTs. We rated the certainty of the evidence using the GRADE approach for the following outcomes: all-cause mortality up to 30 and 120 days, discharged alive (clinical improvement), new need for invasive mechanical ventilation or death (clinical worsening), serious adverse events, adverse events, hospital-acquired infections, and invasive fungal infections. MAIN RESULTS: We included 16 RCTs in 9549 participants, of whom 8271 (87%) originated from high-income countries. A total of 4532 participants were randomised to corticosteroid arms and the majority received dexamethasone (n = 3766). These studies included participants mostly older than 50 years and male. We also identified 42 ongoing and 23 completed studies lacking published results or relevant information on the study design. Hospitalised individuals with a confirmed or suspected diagnosis of symptomatic COVID-19 Systemic corticosteroids plus standard care versus standard care plus/minus placebo We included 11 RCTs (8019 participants), one of which did not report any of our pre-specified outcomes and thus our analyses included outcome data from 10 studies. Systemic corticosteroids plus standard care compared to standard care probably reduce all-cause mortality (up to 30 days) slightly (risk ratio (RR) 0.90, 95% confidence interval (CI) 0.84 to 0.97; 7898 participants; estimated absolute effect: 274 deaths per 1000 people not receiving systemic corticosteroids compared to 246 deaths per 1000 people receiving the intervention (95% CI 230 to 265 per 1000 people); moderate-certainty evidence). The evidence is very uncertain about the effect on all-cause mortality (up to 120 days) (RR 0.74, 95% CI 0.23 to 2.34; 485 participants). The chance of clinical improvement (discharged alive at day 28) may slightly increase (RR 1.07, 95% CI 1.03 to 1.11; 6786 participants; low-certainty evidence) while the risk of clinical worsening (new need for invasive mechanical ventilation or death) may slightly decrease (RR 0.92, 95% CI 0.84 to 1.01; 5586 participants; low-certainty evidence). For serious adverse events (two RCTs, 678 participants), adverse events (three RCTs, 447 participants), hospital-acquired infections (four RCTs, 598 participants), and invasive fungal infections (one study, 64 participants), we did not perform any analyses beyond the presentation of descriptive statistics due to very low-certainty evidence (high risk of bias, heterogeneous definitions, and underreporting). Different types, dosages or timing of systemic corticosteroids We identified one RCT (86 participants) comparing methylprednisolone to dexamethasone, thus the evidence is very uncertain about the effect of methylprednisolone on all-cause mortality (up to 30 days) (RR 0.51, 95% CI 0.24 to 1.07; 86 participants). None of the other outcomes of interest were reported in this study. We included four RCTs (1383 participants) comparing high-dose dexamethasone (12 mg or higher) to low-dose dexamethasone (6 mg to 8 mg). High-dose dexamethasone compared to low-dose dexamethasone may reduce all-cause mortality (up to 30 days) (RR 0.87, 95% CI 0.73 to 1.04; 1269 participants; low-certainty evidence), but the evidence is very uncertain about the effect of high-dose dexamethasone on all-cause mortality (up to 120 days) (RR 0.93, 95% CI 0.79 to 1.08; 1383 participants) and it may have little or no impact on clinical improvement (discharged alive at 28 days) (RR 0.98, 95% CI 0.89 to 1.09; 200 participants; low-certainty evidence). Studies did not report data on clinical worsening (new need for invasive mechanical ventilation or death). For serious adverse events, adverse events, hospital-acquired infections, and invasive fungal infections, we did not perform analyses beyond the presentation of descriptive statistics due to very low-certainty evidence. We could not identify studies for comparisons of different timing and systemic corticosteroids versus other active substances. Equity-related subgroup analyses We conducted the following subgroup analyses to explore equity-related factors: sex, age (< 70 years; ≥ 70 years), ethnicity (Black, Asian or other versus White versus unknown) and place of residence (high-income versus low- and middle-income countries). Except for age and ethnicity, no evidence for differences could be identified. For all-cause mortality up to 30 days, participants younger than 70 years seemed to benefit from systemic corticosteroids in comparison to those aged 70 years and older. The few participants from a Black, Asian, or other minority ethnic group showed a larger estimated effect than the many White participants. Outpatients with asymptomatic or mild disease There are no studies published in populations with asymptomatic infection or mild disease. AUTHORS' CONCLUSIONS: Systemic corticosteroids probably slightly reduce all-cause mortality up to 30 days in people hospitalised because of symptomatic COVID-19, while the evidence is very uncertain about the effect on all-cause mortality up to 120 days. For younger people (under 70 years of age) there was a potential advantage, as well as for Black, Asian, or people of a minority ethnic group; further subgroup analyses showed no relevant effects. Evidence related to the most effective type, dose, or timing of systemic corticosteroids remains immature. Currently, there is no evidence on asymptomatic or mild disease (non-hospitalised participants). Due to the low to very low certainty of the current evidence, we cannot assess safety adequately to rule out harmful effects of the treatment, therefore there is an urgent need for good-quality safety data. Findings of equity-related subgroup analyses should be interpreted with caution because of their explorative nature, low precision, and missing data. We identified 42 ongoing and 23 completed studies lacking published results or relevant information on the study design, suggesting there may be possible changes of the effect estimates and certainty of the evidence in the future.

ABPA sans asthma: an entity to remember.

A male patient in his 20s presented with a cough and a small volume of haemoptysis that lasted a year. He had no other constitutional symptoms and a respiratory examination was suggestive of a consolidation. A chronic infection, such as tuberculosis, was suspected. The routine evaluation showed peripheral eosinophilia with raised serum total IgE. Sputum examination for tuberculosis was negative; hence, a high-resolution CT of the thorax was performed, which revealed bilateral bronchiectasis with high-attenuation mucus plugging. The imaging and blood profiles were in favour of allergic bronchopulmonary aspergillosis, but there was no history suggestive of asthma, and the pulmonary function test was normal. The patient underwent a skin prick test and an allergen-specific IgE test for Aspergillus fumigatus, and both were positive. His bronchoalveolar lavage cultures also grew A. fumigatus, and he responded well to antifungal therapy. This case illustrates the presentation of a rare entity-allergic bronchopulmonary aspergillosis sans asthma.

Treatment of COVID-19 Acute Respiratory Distress Syndrome With a Tabletop Noninvasive Ventilation Device in a Respiratory Intermediate Care Unit.

Objective: To study the outcomes of noninvasive ventilation (NIV) administered through a tabletop device for coronavirus disease 2019 acute respiratory distress syndrome in the respiratory intermediate care unit (RIMCU) at a tertiary care hospital in India. Patients and Methods: We retrospectively studied a cohort of hospitalized patients deteriorating despite low-flow oxygen support who received protocolized management with positive airway pressure using a tabletop NIV device in the RIMCU as a step-up rescue therapy from July 30, 2020 to November 14, 2020. Treatment was commenced on the continuous positive airway pressure mode up to a pressure of 10 cm of H2O, and if required, inspiratory pressures were added using the bilevel positive air pressure mode. Success was defined as weaning from NIV and stepping down to the ward, and failure was defined as escalation to the intensive care unit, the need for intubation, or death. Results: In total, 246 patients were treated in the RIMCU during the study period. Of these, 168 received respiratory support via a tabletop NIV device as a step-up rescue therapy. Their mean age was 54 years, and 83% were men. Diabetes mellitus (78%) and hypertension (44%) were the commonest comorbidities. Treatment was successful with tabletop NIV in 77% (129/168) of the patients; of them, 41% (69/168) received treatment with continuous positive airway pressure alone and 36% (60/168) received additional increased inspiratory pressure via the bilevel positive air pressure mode. Conclusion: Respiratory support using the tabletop NIV device was an effective and economical treatment for coronavirus disease 2019 acute respiratory distress syndrome. Further studies are required to assess the appropriate time of initiation for maximal benefits and judicious utilization of resources.

Inhaled corticosteroids for the treatment of COVID-19.

BACKGROUND: Inhaled corticosteroids are well established for the long-term treatment of inflammatory respiratory diseases such as asthma or chronic obstructive pulmonary disease. They have been investigated for the treatment of coronavirus disease 2019 (COVID-19). The anti-inflammatory action of inhaled corticosteroids might have the potential to reduce the risk of severe illness resulting from hyperinflammation in COVID-19. OBJECTIVES: To assess whether inhaled corticosteroids are effective and safe in the treatment of COVID-19; and to maintain the currency of the evidence, using a living systematic review approach. SEARCH METHODS: We searched the Cochrane COVID-19 Study Register (which includes CENTRAL, PubMed, Embase, ClinicalTrials.gov, WHO ICTRP, and medRxiv), Web of Science (Science Citation Index, Emerging Citation Index), and the WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies to 7 October 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs) evaluating inhaled corticosteroids for COVID-19, irrespective of disease severity, age, sex, or ethnicity. We included the following interventions: any type or dose of inhaled corticosteroids. We included the following comparison: inhaled corticosteroids plus standard care versus standard care (with or without placebo). We excluded studies examining nasal or topical steroids. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. For risk of bias assessment, we used the Cochrane RoB 2 tool. We rated the certainty of evidence using the GRADE approach for the outcomes of mortality, admission to hospital or death, symptom resolution, time to symptom resolution, serious adverse events, adverse events, and infections. MAIN RESULTS: Inhaled corticosteroids plus standard care versus standard care (with/without placebo) - People with a confirmed diagnosis of moderate-to-severe COVID-19 We found no studies that included people with a confirmed diagnosis of moderate-to-severe COVID-19. - People with a confirmed diagnosis of asymptomatic SARS-CoV-2 infection or mild COVID-19 We included three RCTs allocating 3607 participants, of whom 2490 had confirmed mild COVID-19. We analysed a subset of the total number of participants recruited to the studies (2171, 52% female) as some trials had a platform design where not all participants were allocated to treatment groups simultaneously. The included studies were community-based, recruiting people who were able to use inhaler devices to deliver steroids and relied on remote assessment and self-reporting of outcomes. Most people were older than 50 years and had co-morbidities such as hypertension, lung disease, or diabetes. The studies were conducted in high-income countries prior to wide-scale vaccination programmes. A total of 1057 participants were analysed in the inhaled corticosteroid arm (budesonide: 860 participants; ciclesonide: 197 participants), and 1075 participants in the control arm. No studies included people with asymptomatic SARS-CoV-2 infection. With respect to the following outcomes, inhaled corticosteroids compared to standard care: - may result in little to no difference in all-cause mortality (at up to day 30) (risk ratio (RR) 0.61, 95% confidence interval (CI) 0.22 to 1.67; 2132 participants; low-certainty evidence). In absolute terms, this means that for every nine deaths per 1000 people not receiving inhaled corticosteroids, there were six deaths per 1000 people who did receive the intervention (95% CI 2 to 16 per 1000 people); - probably reduces admission to hospital or death (at up to 30 days) (RR 0.72, 95% CI 0.51 to 0.99; 2025 participants; moderate-certainty evidence); - probably increases resolution of all initial symptoms at day 14 (RR 1.19, 95% CI 1.09 to 1.30; 1986 participants; moderate-certainty evidence); - may reduce the duration to symptom resolution (at up to day 30) (by -4.00 days, 95% CI -6.22 to -1.78 less than control group rate of 12 days; 139 participants; low-certainty evidence); - the evidence is very uncertain about the effect on serious adverse events (during study period) (RR 0.51, 95% CI 0.09 to 2.76; 1586 participants; very low-certainty evidence); - may result in little to no difference in adverse events (at up to day 30) (RR 0.78, 95% CI 0.47 to 1.31; 400 participants; low-certainty evidence); - may result in little to no difference in infections (during study period) (RR 0.88, 95% CI 0.30 to 2.58; 400 participants; low-certainty evidence). As studies did not report outcomes for subgroups (e.g. age, ethnicity, sex), we did not perform subgroup analyses. AUTHORS' CONCLUSIONS: In people with confirmed COVID-19 and mild symptoms who are able to use inhaler devices, we found moderate-certainty evidence that inhaled corticosteroids probably reduce the combined endpoint of admission to hospital or death and increase the resolution of all initial symptoms at day 14. Low-certainty evidence suggests that corticosteroids make little to no difference in all-cause mortality up to day 30 and may decrease the duration to symptom resolution. We do not know whether inhaled corticosteroids increase or decrease serious adverse events due to heterogeneity in the way they were reported across the studies. There is low-certainty evidence that inhaled corticosteroids may decrease infections. The evidence we identified came from studies in high-income settings using budesonide and ciclesonide prior to vaccination roll-outs. We identified a lack of evidence concerning quality of life assessments, serious adverse events, and people with asymptomatic infection or with moderate-to-severe COVID-19. The 10 ongoing and four completed, unpublished RCTs that we identified in trial registries address similar settings and research questions as in the current body of evidence. We expect to incorporate the findings of these studies in future versions of this review. We monitor newly published results of RCTs on inhaled corticosteroids on a weekly basis and will update the review when the evidence or our certainty in the evidence changes.

Superior vena caval obstruction: a rare presentation of Behcet's disease.

A 25-year-old Indian man presented with low-grade fever followed by gradually increasing swelling of neck and face. Physical examination showed bilateral neck swelling, facial swelling and dilated veins in the upper chest. Superior vena cava (SVC) obstruction due to an underlying malignancy was suspected. CT thorax showed large saccular aneurysm with thrombosis of bilateral subclavian arteries of which the right one caused external compression of right innominate vein draining into the SVC. A history of recurrent oral and scrotal ulcers was obtained following which skin pathergy test was done, which was suggestive of a diagnosis of Behcet's disease (BD). He responded to treatment with steroids and azathioprine. This report illustrates that rare nonmalignant cause such as BD could also present with SVC obstruction.

To immunosuppress or not: Behcet's syndrome presenting as an eosinophilic pleural effusion.

Etiologic diagnosis of an eosinophilic pleural effusion (EPE) presents a diagnostic challenge when intrapleural air and blood have been ruled out as its proximate causes. Among the causes of EPE, those that require immunosuppression for the underlying disease include connective tissue diseases, sarcoidosis, vasculitis, and eosinophilic pneumonia. We present a case of clinically suspected Behcet's syndrome based on a 10-year history of recurrent multiple oral ulcers and human leukocyte antigen-B51 positivity who presented with only an EPE. Computed tomography pulmonary angiogram ruled out central thoracic vein thrombosis but was inconclusive in ruling out a subsegmental pulmonary embolism. The patient declined immunosuppressants and while on follow-up developed bilateral extensive acute lower limb deep venous thrombosis and pulmonary embolism. Upper infrarenal inferior vena cava demonstrated chronic thrombosis suggestive of its antecedent role in pulmonary embolism-related EPE during the first instance. Behcet's syndrome-related EPE can be associated with venous thromboembolism, and immunosuppressive therapy prevents the subsequent thrombotic episodes.