High-flow nasal oxygen in resource-constrained, non-intensive, high-care wards for COVID-19 acute hypoxaemic respiratory failure: Comparing outcomes of the first v. third waves at a tertiary centre in South Africa.

Background: High-flow nasal oxygen (HFNO) is an accepted treatment for severe COVID-19-related acute hypoxaemic respiratory failure (AHRF). Objectives: To determine whether treatment outcomes at Groote Schuur Hospital, Cape Town, South Africa, during the third COVID-19 wave would be affected by increased institutional experience and capacity for HNFO and more restrictive admission criteria for respiratory high-care wards and intensive care units. Methods: We included consecutive patients with COVID-19-related AHRF treated with HFNO during the first and third COVID-19 waves. The primary endpoint was comparison of HFNO failure (composite of the need for intubation or death while on HFNO) between waves. Results: A total of 744 patients were included: 343 in the first COVID-19 wave and 401 in the third. Patients treated with HFNO in the first wave were older (median (interquartile range) age 53 (46 - 61) years v. 47 (40 - 56) years; p<0.001), and had higher prevalences of diabetes (46.9% v. 36.9%; p=0.006), hypertension (51.0% v. 35.2%; p<0.001), obesity (33.5% v. 26.2%; p=0.029) and HIV infection (12.5% v. 5.5%; p<0.001). The partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2 /FiO2 ) ratio at HFNO initiation and the ratio of oxygen saturation/FiO2 to respiratory rate within 6 hours (ROX-6 score) after HFNO commencement were lower in the first wave compared with the third (median 57.9 (47.3 - 74.3) mmHg v. 64.3 (51.2 - 79.0) mmHg; p=0.005 and 3.19 (2.37 - 3.77) v. 3.43 (2.93 - 4.00); p<0.001, respectively). The likelihood of HFNO failure (57.1% v. 59.6%; p=0.498) and mortality (46.9% v. 52.1%; p=0.159) did not differ significantly between the first and third waves. Conclusion: Despite differences in patient characteristics, circulating viral variant and institutional experience with HFNO, treatment outcomes were very similar in the first and third COVID-19 waves. We conclude that once AHRF is established in COVID-19 pneumonia, the comorbidity profile and HFNO provider experience do not appear to affect outcome. Study synopsis: What the study adds. This study adds to the body of evidence demonstrating the utility of high-flow nasal oxygen (HFNO) in avoiding invasive mechanical ventilation (IMV) in patients with severe COVID-19 hypoxaemic respiratory failure, and shows that this utility remained consistent across different waves of the COVID-19 pandemic.Implications of the study. In resource-constrained settings, HFNO is a feasible non-invasive alternative to IMV and can be employed with favourable and consistent outcomes outside traditional critical care wards. It also confirms that the degree of gas exchange abnormality, and not pre-existing patient-related factors, circulating wave variant or provider experience, is the main predictor of HFNO failure.

Pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension in Cape Town, South Africa.

Background: Pulmonary endarterectomy (PEA) is the only definitive and potentially curative therapy for chronic thromboembolic pulmonary hypertension (CTEPH), associated with impressive improvements in symptoms and haemodynamics. However, it is only offered at a few centres in South Africa. The characteristics and outcomes of patients undergoing PEA in Cape Town have not been reported previously. Objectives: To assess the difference in World Health Organization functional class (WHO-FC) before and at least 6 weeks after surgery. Methods: We interrogated the adult cardiothoracic surgery database at the University of Cape Town between December 2005 and April 2021 for patients undergoing PEA at Groote Schuur Hospital and a private hospital. Results: A total of 32 patients underwent PEA, of whom 8 were excluded from the final analysis owing to incomplete data or a histological diagnosis other than CTEPH. The work-up of these patients for surgery was variable: all had a computed tomography pulmonary angiogram, 7 (29%) had a ventilation/perfusion scan, 5 (21%) underwent right heart catheterisation, and none had a pulmonary angiogram. The perioperative mortality was 4/24 (17%): 1 patient (4%) had a cardiac arrest on induction of anaesthesia, 2 patients (8%) died of postoperative pulmonary haemorrhage, and 1 patient (4%) died of septic complications in the intensive care unit. Among the survivors, the median (interquartile range) improvement in WHO-FC was 2 (1 - 3) classes (p=0.0004); 10/16 patients (63%) returned to a normal baseline (WHO-FC I). Conclusion: Even in a low-volume centre, PEA is associated with significant improvements in WHO-FC and a return to a normal baseline in survivors. Study synopsis: What the study adds. South African patients undergoing pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH) have a marked improvement in functional status, with many returning to a normal functional baseline. However, the small number of patients included in this study indicates that PEA is probably underutilised. Pre- and postoperative assessment is inconsistent, despite availability of established guidelines.Implications of the findings. More patients should be referred to specialist centres for assessment for this potentially curative procedure. Use of guidelines to standardise investigations and monitoring of patients with CTEPH may improve patient selection for surgery.

Cochrane Corner: The use of anticoagulants in patients hospitalised with COVID-19.

Background: In this Cochrane Corner, we highlight the main findings of a Cochrane Review by Flumignan et al. entitled 'Anticoagulants for people hospitalised with COVID-19' and discuss the implications of these findings for research and practice in South Africa. In particular, we underscore the need for additional, high-quality, randomised controlled trials comparing different intensities of anticoagulation in patients with COVID-19 illness. Individuals in the intensive care unit and those hospitalised with another illness who are incidentally found to be infected with SARS-CoV-2 should still only be treated with prophylactic-dose low-molecular-weight heparin. Contributions of the study: This Cochrane Corner summarises findings in a recent systematic review on the use of anticoagulation in people hospitalised with COVID-19, and provides insights on the implications of these findings for implementation by clinicians in South Africa. It highlights the need for clinicians to balance the benefits and harms of providing an anticoagulant, while considering the patients underlying risk for bleeding and thromboembolism.

South African Thoracic Society position statement on the management of non-cystic fibrosis bronchiectasis in adults: 2023.

Background: Bronchiectasis is a chronic lung disorder that affects the lives of many South Africans. Post-tuberculosis (TB) bronchiectasis is an important complication of previous pulmonary TB and a common cause of bronchiectasis in South Africa (SA). No previous statements on the management of bronchiectasis in SA have been published. Objectives: To provide a position statement that will act as a template for the management of adult patients with bronchiectasis in SA. Methods: The South African Thoracic Society appointed an editorial committee to compile a position statement on the management of adult non-cystic fibrosis (CF) bronchiectasis in SA. Results: A position statement addressing the management of non-CF bronchiectasis in adults in SA was compiled. This position statement covers the epidemiology, aetiology, diagnosis, investigations and various aspects of management of adult patients with non-CF bronchiectasis in SA. Conclusion: Bronchiectasis has largely been a neglected lung condition, but new research has improved the outlook for patients. Collaboration between interprofessional team members in patient management is important. In SA, more research into the epidemiology of bronchiectasis, especially post-TB bronchiectasis and HIV-associated bronchiectasis, is required. Abstract: The South African Thoracic Society mandated a multidisciplinary team of healthcare providers to compile a position statement on the management of non-cystic fibrosis bronchiectasis in South Africa (SA). International guidelines on the management of bronchiectasis were reviewed and used as a basis from which the current position statement was compiled. This is the first position statement on the management of adult non-cystic fibrosis bronchiectasis in SA. A description of the epidemiology and aetiology of bronchiectasis is provided, as well as guidance on its diagnosis and management. The position statement provides guidance on the management of bronchiectasis to healthcare providers, policymakers and regulatory authorities.

Asthma in the intensive care unit: A review of patient characteristics and outcomes.

Background: Most asthma-related deaths occur in low- and middle-income countries, and South Africa (SA) is ranked fifth in global asthma mortality. Little is known about the characteristics and outcome of asthma patients requiring intensive care unit (ICU) admission in SA. Objectives: To identify and characterise patients with acute severe asthma admitted to the respiratory ICU at Groote Schuur Hospital, Cape Town, SA, in order to evaluate outcomes and identify predictors of poor outcomes in those admitted. Methods: We performed a retrospective descriptive study of patients with severe asthma admitted to the respiratory ICU at Groote Schuur Hospital between 1 January 2014 and 31 December 2019. Results: One hundred and three patients (110 admission episodes) were identified with an acute asthma exacerbation requiring ICU admission; all were mechanically ventilated. There was a female preponderance (53.6%; n=59/110), with a median (range) age overall of 33 (13 - 84) years. Of all admissions, 40 (36.4%) were current tobacco smokers and 16 (14.5%) patients with a history of substance abuse. Two thirds (60.0%; n=66/110) of the patients were using an inhaled corticosteroid (ICS). No predictors of mortality were evident in multivariate modelling, although those who died were older, and had higher Acute Physiology and Chronic Health Evaluation (APACHE II) scores and longer duration of admission. Only 59 of the surviving 96 individual patients (61.5%) attended a specialist pulmonology clinic after discharge. Conclusion: Among patients admitted to the respiratory ICU at Groote Schuur Hospital for asthma exacerbations, there was a high prevalence of smokers and poor coverage with inhaled ICSs. Although mortality was low compared with general ICU mortality, more needs to be done to prevent acute severe asthma exacerbations. Study synopsis: What the study adds. Intensive care unit (ICU) admission represents the most severe form of exacerbation of asthma. South Africa (SA) has a very high rate of asthma deaths, and this study demonstrates that admission to an ICU with a very severe asthma exacerbation frequently results in a good outcome. However, many of the patients admitted to the ICU were not adequately treated with background asthma medications prior to their admission. Implications of the findings. Death from asthma should be avoidable, and admission to an ICU is not associated with high mortality. Patients are therefore likely to be dying at home or out of hospital. Better education and access to medication and early access to health services rather than improved in-hospital care would potentially alter SA's high asthma mortality.

The optimal management of the patient with COVID-19 pneumonia: HFNC, NIV/CPAP or mechanical ventilation?

The recent pandemic has seen unprecedented demand for respiratory support of patients with COVID-19 pneumonia, stretching services and clinicians. Yet despite the global numbers of patients treated, guidance is not clear on the correct choice of modality or the timing of escalation of therapy for an individual patient. This narrative review assesses the available literature on the best use of different modalities of respiratory support for an individual patient, and discusses benefits and risks of each, coupled with practical advice to improve outcomes. On current data, in an ideal context, it appears that as disease severity worsens, conventional oxygen therapy is not sufficient alone. In more severe disease, i.e. PaO2/FiO2 ratios below approximately 200, helmet-CPAP (continuous positive airway pressure) (although not widely available) may be superior to high-flow nasal cannula (HFNC) therapy or facemask non-invasive ventilation (NIV)/CPAP, and that facemask NIV/CPAP may be superior to HFNC, but with noted important complications, including risk of pneumothoraces. In an ideal context, invasive mechanical ventilation should not be delayed where indicated and available. Vitally, the choice of respiratory support should not be prescriptive but contextualised to each setting, as supply and demand of resources vary markedly between institutions. Over time, institutions should develop clear policies to guide clinicians before demand exceeds supply, and should frequently review best practice as evidence matures.

Interstitial lung disease in patients with connective tissue disease: Subtypes, clinical features and comorbidities in the Western Cape, South Africa.

Background: Interstitial lung disease (ILD) is highly prevalent in patients with connective tissue disease (CTD) and is poorly characterised in South Africa. Objectives: To describe the clinical, serological and radiological features of CTD-ILD and their associations in patients attending a tertiary referral hospital. Methods: A cross-sectional study collating clinical, serological and radiological features of CTD-ILD in patients attending rheumatology and respiratory outpatient clinics in a tertiary referral hospital. Results: Of 124 CTD-ILD patients, 37 (29.8%) had rheumatoid arthritis (RA), 32 (25.8%) systemic sclerosis (SSc) and 55 (44.4%) other autoimmune connective tissue diseases (OCTD). Most patients were female (86.3%), of mixed racial ancestry (75.0%), and the median age was 55 years. Nonspecific interstitial pneumonia (NSIP) was the most common ILD pattern (63.7%), followed by usual interstitial pneumonia (UIP) (26.6%). Overall, 60.5% were current or past smokers, 33.1% had previous pulmonary tuberculosis infection, and 75.6% had gastro-oesophageal reflux disease. Patients with RA were older, had similar frequencies of NSIP and UIP, and had significantly better pulmonary function tests than the SSc and OCTD groups. Within three years of CTD diagnosis, two-thirds of the SSc and OCTD patients and almost half of the RA patients had developed ILD. Clinical features, chest X-rays and pulmonary function tests correlated poorly with high-resolution computerised tomography (HRCT). No case of acute pneumonitis was documented in CTD-ILD patients treated with methotrexate (MTX). Conclusion: We suggest routine HRCT in all newly diagnosed CTD patients, particularly those with SSc and OCTD, where more than two-thirds of the patients had developed ILD within three years of their CTD. The use of MTX was not associated with the development of acute pneumonitis in patients with ILD. Key points: Clinical features, chest X-rays and pulmonary function tests correlated poorly with high-resolution computerised tomography (HRCT).Smoking, environmental toxins, gastro-oesophogeal reflux and previous pulmonary tuberculosis infection were significant comorbidities in CTD-ILD patients.Early screening of ILD with HRCT is recommended, particularly in SSc.Use of MTX before and after ILD diagnosis was not associated with acute pneumonitis.

Patterns of oxygen saturation in prolonged recovery from COVID-19 pneumonia.

During the second wave of the COVID-19 pandemic in South Africa, a recurrent pattern of prolonged recovery after acute COVID-19 pneumonia, characterised by low oxygen saturation levels for >2 weeks, was observed in an intermediate-care facility in Cape Town. A case study together with a series of 12 patients is presented to illustrate this phenomenon, and two types of 'sats gap' are described, which were used by physiotherapists and doctors to monitor daily progress. We attempt to explain this prolonged recovery in terms of the possible pathophysiology, and suggest a number of learning points to guide further research.

Delirium in HIV-infected patients admitted to acute medical wards post universal access to antiretrovirals in South Africa.

BACKGROUND: Delirium is associated with increased mortality and length of hospital stay. Limited data are available from HIV-infected acute hospital admissions in developing countries. We conducted a prospective study of delirium among acute medical admissions in South Africa (SA), a developing country with universal antiretroviral therapy (ART) access and high burdens of tuberculosis (TB) and non-communicable disease. OBJECTIVES: To identify the prevalence of, risk factors for and outcomes of delirium in HIV-infected individuals in acute general medical admissions. METHODS: Three cohorts of adult acute medical admissions to Groote Schuur and Victoria Wynberg hospitals, Cape Town, SA, were evaluated for prevalent delirium within 24 hours of admission. Reference delirium testing was performed by either consultant physicians or neuropsychologists, using the Confusion Assessment Method. RESULTS: The study included 1 182 acute medical admissions, with 318 (26.9%) HIV-infected. The median (interquartile range) age and CD4 count were 35 (30 - 43) years and 132 (61 - 256) cells/µL, respectively, with 140/318 (44.0%) using ART on admission. The prevalence of delirium was 17.6% (95% confidence interval (CI) 13.7 - 22.1) among HIV-infected patients, and delirium was associated with increased inpatient mortality. In multivariable logistic regression analysis, factors associated with delirium were age ≥55 years (adjusted odds ratio (aOR) 6.95 (95% CI 2.03 - 23.67); p=0.002), and urea ≥15 mmol/L (aOR 4.83 (95% CI 1.7 - 13.44); p=0.003), while ART use reduced risk (p=0.014). A low CD4 count, an unsuppressed viral load and active TB were not predictors of delirium; nor were other previously reported risk factors such as non-opportunistic acute infections or polypharmacy. CONCLUSIONS: Delirium is common and is associated with increased mortality in HIV-infected acute medical admissions in endemic settings, despite increased ART use. Older HIV-infected patients with renal dysfunction are at increased risk for inpatient delirium, while those using ART on admission have a reduced risk.

The organisational response of a hospital critical care service to the COVID-19 pandemic: The Groote Schuur Hospital experience.

Background: There are limited data about the coronavirus disease-19 (COVID-19)-related organisational responses and the challenges of expanding a critical care service in a resource-limited setting. Objectives: To describe the ICU organisational response to the pandemic and the main outcomes of the intensive care service of a large state teaching hospital in South Africa. Methods: Data were extracted from administrative records and a prospective patient database with ethical approval. An ICU expansion plan was developed, and resource constraints identified. A triage tool was distributed to referring wards and hospitals. Intensive care was reserved for patients who required invasive mechanical ventilation (IMV). The total number of ICU beds was increased from 25 to 54 at peak periods, with additional non-COVID ICU capacity required during the second wave. The availability of nursing staff was the main factor limiting expansion. A ward-based high flow nasal oxygen (HFNO) service reduced the need for ICU admission of patients who failed conventional oxygen therapy. A team was established to intubate and transfer patients requiring ICU admission but was only available for the first wave. Results: We admitted 461 COVID-19 patients to the ICU over a 13-month period from 5 April 2020 to 5 May 2021 spanning two waves of admissions. The median age was 50 years and duration of ICU stay was 9 days. More than a third of the patients (35%; n=161) survived to hospital discharge. Conclusion: Pre-planning, leadership, teamwork, flexibility and good communication were essential elements for an effective response. A shortage of nurses was the main constraint on ICU expansion. HFNO may have reduced the requirement for ICU admission, but patients intubated after failing HFNO had a poor prognosis. Contributions of the study: We describe the organisational requirements to successfully expand critical care facilities and strategies to reduce the need for invasive mechanical ventilation in COVID-19 pneumonia. We also present the intensive care outcomes of these patients in a resource-constrained environment.

The organisational response of a hospital critical care service to the COVID-19 pandemic: The Groote Schuur Hospital experience

Background. There are limited data about the coronavirus disease-19 (COVID-19)-related organisational responses and the challenges of expanding a critical care service in a resource-limited setting.Objectives. To describe the ICU organisational response to the pandemic and the main outcomes of the intensive care service of a large state teaching hospital in South Africa.Methods. Data were extracted from administrative records and a prospective patient database with ethical approval. An ICU expansion plan was developed, and resource constraints identified. A triage tool was distributed to referring wards and hospitals. Intensive care was reserved for patients who required invasive mechanical ventilation (IMV). The total number of ICU beds was increased from 25 to 54 at peak periods, with additional non-COVID ICU capacity required during the second wave. The availability of nursing staff was the main factor limiting expansion. A ward-based high flow nasal oxygen (HFNO) service reduced the need for ICU admission of patients who failed conventional oxygen therapy. A team was established to intubate and transfer patients requiring ICU admission but was only available for the first wave. Results. We admitted 461 COVID-19 patients to the ICU over a 13-month period from 5 April 2020 to 5 May 2021 spanning two waves of admissions. The median age was 50 years and duration of ICU stay was 9 days. More than a third of the patients (35%; n=161) survived to hospital discharge. Conclusions. Pre-planning, leadership, teamwork, flexibility and good communication were essential elements for an effective response. A shortage of nurses was the main constraint on ICU expansion. HFNO may have reduced the requirement for ICU admission, but patients intubated after failing HFNO had a poor prognosis.

The mechanics of setting up a COVID-19 response: Experiences of the COVID-19 epidemic from Groote Schuur Hospital, Cape Town, South Africa.

The SARS-CoV-2 pandemic has challenged the provision of healthcare in ways that are unprecedented in our lifetime. Planning for the sheer numbers expected during the surge has required public hospitals to de-escalate all non-essential clinical services to focus on COVID-19. Western Cape Province was the initial epicentre of the COVID-19 epidemic in South Africa (SA), and the Cape Town metro was its hardest-hit geographical region. We describe how we constructed our COVID-19 hospital-wide clinical service at Groote Schuur Hospital, the University of Cape Town's tertiary-level teaching hospital. By describing the barriers and enablers, we hope to provide guidance rather than a blueprint for hospitals elsewhere in SA and in low-resource countries that face similar challenges now or during subsequent waves.

Clinical management of COVID-19: Experiences of the COVID-19 epidemic from Groote Schuur Hospital, Cape Town, South Africa.

The SARS-CoV-2 pandemic has presented clinicians with an enormous challenge in managing a respiratory virus that is not only capable of causing severe pneumonia and acute respiratory distress syndrome, but also multisystem disease. The extraordinary pace of clinical research, and particularly the surge in adaptive trials of new and repurposed treatments, have provided rapid answers to questions of whether such treatments work, and has resulted in corticosteroids taking centre stage in the management of hospitalised patients requiring oxygen support. Some treatment modalities, such as the role of anticoagulation to prevent and treat potential thromboembolic complications, remain controversial, as does the use of high-level oxygen support, outside of an intensive care unit setting. In this paper, we describe the clinical management of COVID-19 patients admitted to Groote Schuur Hospital, a major tertiary level hospital at the epicentre of South Africa's SARS-CoV-2 epidemic during its first 4 months.

Tuberculosis burden in stage 5 chronic kidney disease patients undergoing dialysis therapy at Livingstone Hospital, Port Elizabeth, South Africa.

BACKGROUND: Tuberculosis (TB) is currently the leading cause of death from a single infectious agent worldwide. Patients who receive dialysis are particularly vulnerable to TB infection owing to immune dysfunction. Nonetheless, there is a paucity of incidence data on dialysis patients infected with TB in high-burden countries, such as South Africa (SA). OBJECTIVES: To determine the incidence of TB in prevalent chronic kidney disease stage 5 (CKD-5D) patients on dialysis at a single centre in Eastern Cape Province, SA, and to identify the risk factors associated with TB infection. METHODS: We conducted a retrospective cohort study of all consenting CKD-5D patients between April 2010 and March 2014 at Livingstone Hospital Renal Unit, Port Elizabeth, the Eastern Cape. TB was defined as definite or probable according to World Health Organization (WHO) criteria, and the cohort was split into those who developed TB (TB+) and those who did not (TB-). RESULTS: One hundred and eleven patients were enrolled - predominantly black Africans (73%) and women (53%); the mean age (standard deviation (SD)) was 42 (9.8) years. The prevalence of HIV infection was 11%, all patients were receiving antiretroviral treatment and all had suppressed viral loads. Sixty-eight patients were on haemodialysis and 43 on peritoneal dialysis. Nineteen patients were diagnosed with 20 episodes of TB; 14 cases were pulmonary TB and 6 cases extrapulmonary TB. Of the patients with TB, 2 were HIV-infected, 7 (35%) were definite TB cases and 13 (65%) were probable cases. The calculated incidence rate was 4 505/100 000 patient years. Only informal housing (30% in TB+ v. 12% in TB-; p=0.042) and a history of hospitalisation (90% v. 76%, respectively; p=0.042) were significantly associated with a diagnosis of TB. CONCLUSIONS: Dialysis patients in the Eastern Cape region of SA are at extremely high risk of acquiring TB, with an incidence rate 4.1 times that of the local population and >5 times that of the general SA population. Only informal housing and a history of hospitalisation were identified as positive risk factors for TB in this young population with a low HIV prevalence. Isoniazid prophylaxis in this high-risk group might be of benefit, but further studies are required to inform such treatment.

Prolonged treatment of COVID-19 pneumonia with high-flow nasal oxygen: A story of oxygen and resilience.

The COVID-19 pandemic has placed significant strain on the oxygen delivery infrastructure of health facilities in resource-constrained health systems. In this case report, we describe a patient with severe COVID-19 pneumonia who was managed with high-flow nasal oxygen for 40 days, with an eventual successful outcome. We discuss the oxygen delivery infrastructure needed to offer this intervention, as well as the psychosocial impact on those undergoing treatment.

The mechanics of setting up a COVID-19 response: Experiences of the COVID-19 epidemic from Groote Schuur Hospital, Cape Town, South Africa

The COVID-19 pandemic has challenged the provision of healthcare in ways that are unprecedented in our lifetime. Planning for the sheer numbers expected during the surge has required public hospitals to de-escalate all non-essential clinical services to focus on COVID-19. Western Cape Province was the initial epicentre of the COVID-19 epidemic in South Africa (SA), and the Cape Town metro was its hardest-hit geographical region. We describe how we constructed our COVID-19 hospital-wide clinical service at Groote Schuur Hospital, the University of Cape Town's tertiary-level teaching hospital. By describing the barriers and enablers, we hope to provide guidance rather than a blueprint for hospitals elsewhere in SA and in low-resource countries that face similar challenges now or during subsequent waves

Relationship between chest radiographic characteristics, sputum bacterial load, and treatment outcomes in patients with extensively drug-resistant tuberculosis.

BACKGROUND: Data about the relationship between chest radiographs and sputum bacillary load, with treatment outcomes, in patients with extensively drug-resistant tuberculosis (XDR-TB) from HIV/TB endemic settings are limited. METHODS: Available chest radiographs from 97 South African XDR-TB patients, at the time of diagnosis, were evaluated by two independent readers using a validated scoring system. Chest radiograph findings were correlated with baseline sputum bacillary load (smear-grade and culture time-to-positive in MGIT), and prospectively ascertained clinical outcomes (culture conversion and all-cause mortality). RESULTS: Radiographic bilateral lung disease was present in 75/97 (77%). In the multivariate analysis only a higher total radiographic score (95% CI) was associated with higher likelihood of death [1.16 (1.05-1.28) p=0.003], and failure to culture convert [0.85 (0.74-0.97) p=0.02]. However, when restricting analyses to HIV-infected patients, disease extent, cavitation, and total radiographic scores were not associated with mortality or culture-conversion. Finally, cavitary, disease extent, and total radiographic scores all positively correlated with bacterial load (culture time-to-positive). CONCLUSIONS: In endemic settings, XDR-TB radiological disease extent scores are associated with adverse clinical outcomes, including mortality, in HIV uninfected persons. These data may have implications for clinical and programmatic decision-making and for evaluation of new regimens in clinical trials.

Acute cellular rejection in lung transplantation.

Lung transplantation is an important therapy for end-stage respiratory failure in patients who have exhausted other therapeutic options. The lung is unique among solid-organ transplants in that it is exposed to the outside environment, and undergoes continuous stimulation from infectious and non-infectious agents, which may play a part in upregulating the immune response to the allograft. Despite induction immunosuppression and the use of aggressive maintenance regimens, acute allograft rejection is still a major problem, especially in the first year after transplant, with important diagnostic and therapeutic challenges. As well as being responsible for early graft failure and death, acute rejection also initiates alloimmune responses that predispose patients to chronic lung allograft dysfunction, in particular bronchiolitis obliterans syndrome. Cellular responses to human leukocyte antigens (HLAs) on the allograft have traditionally been considered the main mechanism of acute rejection, although the influence of humoral immunity is increasingly recognised. Here, we present two cases of acute cellular rejection (ACR) in the early post-transplant period and review the pathophysiology, diagnosis, clinical presentation and treatment of ACR.