Acute respiratory distress syndrome due to severe pulmonary tuberculosis treated with extracorporeal membrane oxygenation: A case report and review of the literature


Abstract

Mortality in patients with pulmonary tuberculosis remains high, especially in those who develop acute respiratory distress syndrome (ARDS). We report on a-48-year-old man with ARDS due to severe pulmonary tuberculosis who was rescued by extracorporeal membrane oxygenation (ECMO). He was initially hospitalized in the intensive care unit and noninvasive positive-pressure ventilation started. He was also administered anti-tuberculosis drugs and received systemic corticosteroid therapy. Six days later, further deterioration of gas exchange prompted the decision to intubate. However, he experienced progressive deterioration of arterial oxygenation despite conventional ventilatory support. We therefore decided to administer ECMO on day 9. After initiation of these treatments and ECMO support, pulmonary infiltrate and oxygenation status gradually improved and ECMO was discontinued on day 52. The patient was finally discharged from our hospital without severe disability. ECMO should be considered one of the treatment options for the management of ARDS due to severe pulmonary tuberculosis.

Abbreviations

  • ARDS, acute respiratory distress syndrome;
  • ECMO, extracorporeal membrane oxygenation;
  • ICU, intensive care unit;
  • MV, mechanical ventilation;
  • PTB, pulmonary tuberculosis

1. Introduction

In-hospital mortality of tuberculosis patients remains high, especially among those requiring admission to the intensive care unit (ICU) and mechanical ventilation (MV)[1] and [2]. Tuberculosis patients requiring ICU care may also develop acute respiratory distress syndrome (ARDS) [1] and [3]. In the management of patients with ARDS, extracorporeal membrane oxygenation (ECMO) has been successfully used as salvage therapy. ARDS severe enough to require ECMO support is estimated to occur in nearly 5 to 10 cases per million population per year [4]. The effectiveness of ECMO in ARDS patients with pneumonia, influenza A (H1N1) and trauma has recently been described but is less certain in ARDS patients with pulmonary tuberculosis (PTB) [5] and [6]. We report a patient with ARDS due to severe PTB who was rescued by ECMO.

2. Case report

A-48-year-old man was admitted to our hospital because of dyspnea. His sputa were strongly smear-positive and the mycobacteria obtained from culture were identified as M. tuberculosis. Routine blood tests showed white blood cell count of 12800/mm3, platelets of 35.0 × 104/mm3, C-reactive protein of 22.0 mg/dl, albumin level of 1.9 g/dl and a negative HIV ELISA test. His chest X-ray and computed tomography showed diffuse bilateral infiltration and cavity (Fig. 1A, B), and blood gas test showed PaO2/FiO2 131.0. This patient was initially hospitalized in the ICU and noninvasive positive-pressure ventilation started. Anti-tuberculosis drugs, including isoniazid, refampicin, streptomycin and pyrazinamide; antibiotics including meropenem and ciprofloxacin; and intravenous methylprednisolone (1.0 mg/kg/day) were introduced.

Chest X-ray and computed tomography images. (A) and (B): On the day of admission ...
Fig. 1.

Chest X-ray and computed tomography images. (A) and (B): On the day of admission to our hospital. (C) and (D): 3 days after the discontinuation of extracorporeal membrane oxygenation. (E) and (F): 2 weeks after weaning from mechanical ventilation.

Six days later, further deterioration of gas exchange prompted the decision to intubate and steroid pulse therapy consisting of intravenous methylprednisolone (1000 mg/day for 3 days) followed by intravenous methylprednisolone (1.0 mg/kg/day) was administered. However, on the 3rd day of intubation arterial blood gas analyses showed severe hypoxemia (PaO2/FiO2 60.4) refractory to conventional MV, and we decided to administer veno-venous ECMO. Ventilator settings were adjusted to provide lung rest (pressure controlled ventilation with peak pressure of 20 cmH2O, PEEP of 10 cmH2O, and ventilation frequency of 8 per minute).

Hemoptysis was observed on day 27 after the start of ECMO but ceased with adjustment to a lower dosage of heparin. No other ECMO-related major complications were evident during treatment. The pulmonary infiltrate and oxygenation status gradually improved (Fig. 1C, D, E, F), and the systemic corticosteroid was tapered. ECMO was discontinued on day 52 and we successfully weaned the patient from MV 106 days after the start of administration of ECMO. After a hospital stay and rehabilitation of 10 months, he was discharged from our hospital without severe disability.

3. Discussion

ECMO is considered one of the treatment options for severe ARDS [5], [6] and [7]. ARDS is an infrequent but serious complication of PTB [8]. The mortality of ARDS patients with PTB requiring MV is relatively high compared with that of patients with ARDS from other causes [9]. Five patients with acute respiratory failure due to PTB were recently reported to be successfully rescued by ECMO [10], [11], [12], [13], [14] and [15] (Table 1). Given the high mortality rate of ARDS patients with PTB, ECMO could be an important treatment option.

Table 1.Previously reported patients with pulmonary tuberculosis treated with ECMO.

Age Sex Underlying condition Treatment Use of corticosteroid Length of ECMO Outcome Author/year
58 F None None None 5 days Death Homan W 1975 [10]
15 F None INH/RFP/EB/PZA None 6 days (152 h) Recovery Petrillo TM 2001 [11]
20 M None INH/RFP/EB/PZA None 89 days Recovery Mauri T 2012 [12]
14 F Histiocytic hemophagocytosis INH/RFP/EB/PZA Methylprednisolone 2mg/kg/day 6 days recovery Monier B 2013 [13]
24 F Laryngeal papilloma INH/RFP/EB/PZA Methylprednisolone 250mg/day 36 days Recovery Andresen M 2013[14]
20 M None INH/RFP/EB/PZA None 89 days Recovery Cogliandro V 2014 [15]
EB = ethambutol; ECMO = extracorporeal membrane oxygenation; INH = isoniazid; PZA = pyrazinamide; RFP = refampicin.

An innovative aspect of this case is the duration of ECMO, which was longer than that in ARDS from other causes. The clinical courses of patients with PTB often become indolent and the healing rate of PTB is characteristically slow. In addition, our patient showed severe hypoxia compared with previous patients with ARDS from PTB treated with MV [9]. A previous study reported that PTB patients with greater disease extent and severity showed persistent inflammation and required longer treatment [16]. While there is some concern that long-term use of ECMO may lead to a higher risk of complications, recent progress in the techniques and equipment used in ECMO have made prolonged ECMO support feasible. In fact, the survival of prolonged ECMO patients has improved significantly compared with previous years [17]. Another report supporting this described a case of indolent infection caused by Nocardia cyriacigeorgica and Burkholderia cepacia that was rescued by ECMO [18].

In this patient the adjunctive use of systemic corticosteroid therapy led to rapid clinical improvement and allowed us to wean the patient off ECMO earlier. Andresen et al. similarly reported that systemic corticosteroid therapy during ECMO support led to progressive improvement of respiratory function [14]. Several other studies have also suggested the effectiveness of adjunctive use of corticosteroids for PTB [19],[20] and [21]. The steroid dose we used in this case was higher than that in the previous reports. Although evidence for high dose steroid therapy for PTB is still lacking, our aim in using this high dose was to get quicker and stronger results and to decrease the need for long-term steroid use [22].

In conclusion, we have reported here a patient with ARDS due to severe PTB who was rescued by ECMO. The healing rate of PTB is characteristically slow, which may lead the long-term use of ECMO. There is increasing recent evidence for the effectiveness of ECMO, and advances in the techniques and devices have made prolonged ECMO support feasible. ECMO should therefore be considered among the treatment options in patients with ARDS due to severe PTB when conventional ventilatory support is inadequate.

Ultrasonography assessment of congenital renal anomalies in children with congenital heart diseases


Ultrasound (US) assessment of renal anomalies in children requiring pediatric cardiac surgery is not a standard practice. This study aimed to study the role of bedside US performed by intensivists to detect occult renal anomalies associated with congenital heart disease (CHD). Prospective descriptive study for 100 consecutive children with CHD admitted to Pediatric Cardiac Intensive Care Unit (PCICU) from Januarry 1st, 2015 through June, July 2015. Ultrasound of kidneys was performed initially by trained pediatric cardiac intensivists to ascertain the presence of both kidneys in renal fossae and to check for gross kidney anomalies. After screening of 100 consecutive children with CHD with renal US, we identified in 94 cases (94%) normal right and left kidney in the standard sonographer shape in the renal fossae. In 6 cases further investigation revealed ectopic kidney in 3 patients (50%), solitary functional kidney in 2 patients (33.4%) and bilateral grade IV hydronephrosis in one patient (16.6%). Urinary tract infection developed peri-operatively in 66% of the cases with kidney anomalies. No significant renal impairment was noted in these patients post-surgery. We observed no specific association between the type of renal anomaly and specific CHD. Renal US in children with CHD demonstrated prevalence of associated congenital renal anomalies in 6% of children undergoing cardiac surgery. The presence of occult kidney anomalies did not impact the kidney function or the short term outcome after cardiac repair except for an increased risk of urosepsis. Performing renal US should be a standard practice in all children with CHD.

Impact of 18F-FDG PET/CT staging on management and prognostic stratification in head and neck squamous cell carcinoma


Highlights

Positron emission tomography/computed tomography (PET/CT) staging changed the management plan in 39 (15.7%) of 248 patients with head and neck squamous cell carcinoma (HNSCC).

It largely caused that PET/CT detected metastatic disease and second primary cancers better than conventional workups (CWU).

PET/CT staging was significantly more predictive of survival outcomes than CWU staging.

PET/CT added important staging information that improved management and prognostic stratification in HNSCC.


Abstract

Background

Accurate assessment of the extent of cancer is essential for appropriate treatment planning and outcome prediction. This study prospectively evaluated whether adding18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) to the routine initial staging practice in head and neck squamous cell carcinoma (HNSCC) improved management and prognosis.

Methods

All consecutive patients with newly diagnosed HNSCC who presented in October 2010 – December 2012 underwent conventional workups (CWU) followed by PET/CT. The clinical stage and management plans before and after PET/CT were compared. PET/CT was deemed to have no/low, moderate, and high impact on management planning depending on whether PET/CT changed the treatment modality or goal. The appropriateness of PET/CT staging and management impact was confirmed by histopathology and clinical follow-up, and its association with survival was analysed.

Findings

Of the 248 patients, PET/CT changed the Tumour Node Metastasis (TNM) classification in 79 (31.9%). In the patients with discordant staging, PET/CT staging was significantly more sensitive and accurate than CWU staging (both P < 0.001). PET/CT had high or moderate impact on management in 39 (15.7%) patients. Patients with PET/CT upstaged disease had significantly worse progression-free survival (PFS) and overall survival (OS) than patients with no CWU-stage changes (3-year PFS = 56.8% versus 74.5%, P = 0.043; 3-year OS = 61.3% versus 85.3%, P = 0.006). Multivariate analyses revealed that PET/CT staging and second primary cancer were independent predictive factors for both PFS and OS (P < 0.05, each).

Interpretations

18F-FDG PET/CT added important staging information that improved management and prognostic stratification in HNSCC.

Paraneoplastic epilepsy


Highlights

Paraneoplastic epilepsy is characteristic in clinical presentation, treatment, and prognosis.

Paraneoplastic epilepsy is often associated with distinct onconeuronal antibodies.

Recognizing onconeuronal antibodies will help in the diagnosis of paraneoplastic epilepsy and guide the treatment.


Abstract

Epilepsy can be a manifestation of paraneoplastic syndromes which are the consequence of an immune reaction to neuronal elements driven by an underlying malignancy affecting other organs and tissues. The antibodies commonly found in paraneoplastic encephalitis can be divided into two main groups depending on the target antigen: 1) antibodies against neuronal cell surface antigens, such as against neurotransmitter (N-methyl-d-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), gamma-aminobutyric acid (GABA)) receptors, ion channels (voltage-gated potassium channel (VGKC)), and channel-complex proteins (leucine rich, glioma inactivated-1 glycoprotein (LGI1) and contactin-associated protein-2 (CASPR2)) and 2) antibodies against intracellular neuronal antigens (Hu/antineuronal nuclear antibody-1 (ANNA-1), Ma2/Ta, glutamate decarboxylase 65 (GAD65), less frequently to CV2/collapsin response mediator protein 5 (CRMP5)). In this review, we provide a comprehensive survey of the current literature on paraneoplastic epilepsy indexed by the associated onconeuronal antibodies. While a range of seizure types can be seen with paraneoplastic syndromes, temporal lobe epilepsy is the most common because of the association with limbic encephalitis. Early treatment of the paraneoplastic syndrome with immune modulation/suppression may prevent the more serious potential consequences of paraneoplastic epilepsy.

Antioxidant and antitumor efficacy of Luteolin, a dietary flavone on benzo(a)pyrene-induced experimental lung carcinogenesis


Highlights

Chemopreventive effect of luteolin, a dietary flavone, is evaluated against B(a)P induced lung cancer.

Luteolin restored the tumor markers enzymes, lipid peroxidation and antioxidant levels.

Luteolin protected the histoarchitecture of lungs in B(a)P intoxicated mice.

Luteolin treatment downregulated the PCNA, CYP1A1 and NF-κB expression.


Abstract

The present study is designed to assess the antioxidant and antitumor potential of luteolin against benzo(a)pyrene [B(a)P]-induced lung carcinogenesis in Swiss albino mice. Here, we reported that oral administration of B(a)P (50 mg/kg body weight) to mice resulted in raised lipid peroxides (LPO), lung specific tumor markers such as carcinoembryonic antigen (CEA) and neuron specific enolase (NSE) with concomitant decrease in the levels of both enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione-s-transferase (GST), and non-enzymatic antioxidants such as reduced glutathione (GSH), vitamin E and vitamin C. Luteolin treatment (15 mg/kg body weight, p.o) significantly counteracted all these alterations and maintained cellular normalcy. Moreover, assessment of protein expression levels by western blot analysis revealed that luteolin treatment effectively negates B(a)P-induced upregulated expression of proliferating cell nuclear antigen (PCNA), cytochrome P450 1A1 (CYP1A1) and nuclear factor-kappa B (NF-κB). Furthermore, histopathology of lung tissue and immunohistochemistry of CYP1A1 were carried out to substantiate the anti- lung cancer effect of luteolin. Overall, these findings confirm the chemopreventive potential of luteolin against B(a)P induced lung carcinogenesis.

Liquid biopsy-based clinical research in early breast cancer


Highlights

This study evaluates the concept of targeting minimal residual disease (presence of circulating tumour cells).

Liquid-based biopsy clinical research is feasible.

This is the first study of its kind in adjuvant therapy of breast cancer.


Abstract

There is increasing evidence that breast cancer evolves over time under the selection pressure of systemic treatment. Today, treatment decisions in early breast cancer are based on primary tumour characteristics without considering the disease evolution. Chemoresistant micrometastatic disease is poorly characterised and thus it is not used in current clinical practice as a tool to personalise treatment approaches. The detection of chemoresistant circulating tumour cells (CTCs) has been shown to be associated with worse prognosis in early breast cancer. The ongoing Treat CTC trial is the first international, liquid biopsy-based trial evaluating the concept of targeting chemoresistant minimal residual disease: detection of CTCs following adjuvant chemotherapy (adjuvant cohort) or neoadjuvant chemotherapy in patients who did not achieve pathological complete response (neoadjuvant cohort). This article presents the rational and design of this trial and the results of the pilot phase after 350 patients have been screened and provides insights that might provide information for future trials using the liquid biopsy approach as a tool towards precision medicine

Screening for type 1 diabetes: not ready for clinical implementation


Screening programs are not standard practice — will screening provide any value in the clinical setting?

If type 1 diabetes could be prevented, millions of people throughout the world could live longer, healthier lives free from the burden and complications of managing the disease.

The past two decades have seen several diabetes breakthroughs — researchers have discovered genetic and immune factors that contribute to risk, for example — but also a growing incidence of disease. About one in every 400 to 600 children in the United States had diabetes in 2005.

Continued research into type 1 diabetes has allowed researchers to identify individuals at risk and design studies and clinical trials to test strategies aimed at preventing or delaying the onset of the disease. A population-wide screening program for type 1 diabetes is not yet standard practice; will it ever become standard to screen for type 1 diabetes?

Several experts Endocrine Today interviewed said screening for type 1 diabetes should, at present, only be used for research purposes.

“Screening should only be a research endeavor,” said Dorothy Becker, MBBCh, director of the Diabetes Program at the Children’s Hospital of Pittsburgh. “There is no evidence that screening, from a clinical point of view, is of any value – particularly as there is no known intervention.” The only clinically important reason to screen would be for a patient at very high risk — for example 80% — and then checking their blood glucose or performing oral glucose tolerance tests with them more often, according to Becker, chief of endocrinology at Children’s Hospital.

Dorothy Becker, MBBCh
Dorothy
Becker

“At this stage, screening is really more case finding to understand more about the natural history of disease, to understand the mechanisms leading to disease and to enroll patients in intervention studies,”Desmond Schatz, MD, said in an interview.

The World Health Organization recommends clinical screening only for diseases for which there are effective prevention or treatments.

“Once we have a therapy that can delay or prevent the disease, then routine screening would be absolutely justifiable,” said Schatz, medical director of the Diabetes Center at University of Florida.

Joseph Wolfsdorf, MB, MBBCh, had a similar point of view. “We are not at the point where routine screening is warranted,” said the clinical director of the division of endocrinology at the Children’s Hospital in Boston. “Until we have a viable intervention, screening should not be a routine part of medical practice.”

Screening for prevention, intervention

“Although we have made wonderful progress in understanding the natural history of the prediabetic period, we have really learned little about the underlying mechanisms leading to the disease,” Schatz said.

Desmond Schatz, MD
Desmond Schatz, MD, is the Medical Director of the Diabetes Center at the University of Florida.

Photo by Sarah Kiewel

“We don’t really understand why this suicide of the pancreas occurs or why the pancreas is in such a difficult position for us to access,” he said.

Some experts believe that the acute onset of diabetes renders screening unnecessary, but studies indicate that the latent autoimmunity in the prediabetic period that typically precedes diagnosis makes screening and prevention through immune modulation a tangible goal.

In most cases, a blood test can identify risk of developing type 1 diabetes, based on measurement of antibodies to biochemically characterized antigens like insulin, glutamic acid decarboxylase (GAD), islet antigen 2 and zinc transporter 8 (ZnT8). Previous studies have indicated that individuals who are positive for two autoantibodies have a 80% cumulative disease risk over the following four years and individuals who are positive for three autoantibodies have an even higher risk. Researchers are also examining genetic predisposition in certain alleles of immune response genes, such as human leukocyte antigen (HLA) genotyping.

Earlier this year, Jay M. Sosenko, MD, and colleagues introduced a risk score for diabetes based on an algorithm factoring in age, BMI, fasting C-peptide and total fasting glucose. The risk score appeared to accurately predict disease in islet cell autoantibody-positive relatives of affected patients enrolled in the Diabetes Prevention Trial-Type 1. A previously published report from the Childhood Diabetes in Finland study demonstrated that age, HLA-defined diabetes predisposition, increasing number of autoantibodies, reduced first-phase insulin response and decreased insulin sensitivity were predictors of progression to diabetes in a subgroup of autoantibody-positive siblings. Young age was a common feature in both studies, which indicates that initiation of the disease process early in life resulted in rapid progression to overt disease, according to Mikael Knip, MD, who wrote a 2008 editorial about this topic inDiabetes Care.

“Is there a rationale beyond research studies for screening siblings of affected subjects who have a relative risk of type 1 diabetes at least 10 times higher than that in the general population (with the absolute risk in the range of 6% to 10%)?” Knip wrote. “What would be the optimal screening strategy?”

The search for an intervention

“We do not have a lot [of data] to offer people at the moment,” Janet H. Silverstein, MD, chief, department of pediatrics, division of endocrinology, at the University of Florida, Gainesville, told Endocrine Today.

Several studies to screen newborns from the general population and high-risk individuals are currently underway (see sidebar). These trials are conducted with the goal of identifying genes or triggers of autoimmunity and, ultimately, to test interventions to prevent or delay the disease.

Much of the research is carried out through TrialNet, a network of 18 clinical centers and various screening sites throughout the world. Several research efforts are currently in recruitment, such as the Nutritional Intervention to Prevent Type 1 Diabetes Study, which will examine docosahexaenoic acid (DHA) given to pregnant mothers and infants younger than 5 months. Other studies include the Oral Insulin for Prevention of Type 1 Diabetes Study, and the Natural History Study, in which researchers will investigate the risk for diabetes in close relatives of patients with type 1 diabetes.

Janet H. Silverstein, MD
Janet H. Silverstein

Some primary prevention trials are examining environmental exposures in infants who carry the high-risk genotypes identified by genetic screening. The TEDDY trial will look at environmental triggers, TRIGR will study the elimination of cow’s milk from diets, and the Pre-Point study will examine immunomodulation with human oral insulin. Another, DIPP, or the Diabetes Prediction and Prevention Project, will assess newborns for increased genetic risk. Since the project was launched in 1994, more than 8,500 children at increased genetic risk have participated in the study and more than 110 have progressed to clinical diabetes.

To date, the DTP-1 and ENDIT trials, large-scale randomized controlled trials examining the prevention or delay of type 1 diabetes, have failed to demonstrate a treatment effect. However, these trials have shown that individuals with islet autoantibodies have a variable period of mild hyperglycemia that precedes overt insulin dependence by months, sometimes years.

Published data from DAISY suggested that identification of individuals at increased risk and prospective monitoring resulted in early diagnosis and avoidance of severe metabolic decompensation at diagnosis among patients who progressed to overt diabetes.

It all comes down to the physicians, said Silverstein, an Endocrine Today editorial board member. “There are a limited number of people who are eligible for these trials, so we need to make people aware that they exist and how they can participate,” she said. “We, as physicians, need to enroll patients, take the time to explain why we are drawing blood and explain the potential benefits.”

Ethical considerations

“If you discover someone who is positive, what do you do with the information?” Wolfsdorf said.

Opponents of a population-wide screening program argue that tests raise ethical considerations: induced stress, cost, lifestyle changes and potential effects on insurability.

Lainie Friedman Ross, MD
Lainie Friedman Ross

“Even our language of calling a patient ‘high risk’ is confusing,” Lainie Friedman Ross, MD, PhD, toldEndocrine Today. “Screening for type 1 diabetes does not tell a patient yes or no that he or she has the disease — it only tells the patient he/she is at increased risk. More than 90% of people who are identified as high risk will never go on to develop the disease,” according to Ross, who holds the Carolyn and Matthew Bucksbaum Chair of Clinical Ethics at the University of Chicago. “That is, for every 100 individuals labeled as high risk, fewer than 10 develop the disease, but all 100 worry for years. It is wrong to impose such stress on an unsuspecting population,” she said.

However, in high-risk families, a negative genetic test means that a particular child is not at increased risk. This can be reassuring to the parents. And, if the child does not have the gene, the parents can be prepared, be vigilant for symptoms, and know what to expect. Thus, predictive testing should be restricted to high-risk families as part of rigorous research protocols.

Paula Simonen, PhLic, and colleagues assessed the anxiety, emotions and coping behaviors of parents one week after they received the results of their newborn’s genetic test for type 1 diabetes. More than 90% of parents thought it was good to know about their child’s risk. However, 55% of mothers and 37% of fathers of high-risk infants expressed modest worry and increased anxiety. These parents also had negative thoughts of diabetes risk and expressed avoidance of coping attitudes. The researchers concluded that identifying the few parents with strong anxiety may help focus intensified counseling (see chart).

“We should not introduce risk identification when data show that parents of newborns are already anxious. Newborn screening has been a remarkable success in the history of public health interventions. We should not jeopardize public support of newborn screening programs by piggybacking it with research that merely identifies probabilistic risks,” Ross wrote in an Archives of Pediatric and Adolescent Medicine editorial last year.

Yet, Simonen et al said that increased anxiety after receiving risk information dissipates over time, and there is considerable variation based on race/ethnicity and education level.

Anxiety Scores of Parents of Newborns at High Risk and Low Risk for Type 1 Diabetes

Other barriers to screening

One problem with antibody screening is that it can change over time, according to Wolfsdorf. “If [a test] were negative today, you cannot tell a patient that they will never develop diabetes because six months from now or 10 years from now the antibody test could become positive,” he said during an interview.

“It is simply a marker,” he said. “It’s like if you look out the window and see smoke on the horizon. All that tells you is there is a fire somewhere. Antibody tests merely indicate that there is an active immunological process, but they do not provide definitive information about the future, which can only be obtained by careful clinical and biochemical monitoring and follow-up.”

According to recent estimates from the American Diabetes Association, diabetes care costs more than $174 billion annually. A screening program must carry a good cost-benefit ratio before its clinical implementation can be justified. Researchers with the DIPP Study evaluated the costs of two different population-based approaches to predict type 1 diabetes: a targeted DIPP method of genetic screening vs. repeated immunological follow-up of all newborns. During 10 years of follow-up, total direct cost per child was $261 with the targeted DIPP method compared with $680 with the non-targeted method. The researchers concluded that targeted prediction based on genetic screening was a cost-saving method.

Still, the pros of screening for type 1 diabetes outweigh the cons, according to Schatz.

DAISY Study

Look outside the box

“We have to apply new technology, we have to continue to think outside the box and explore new therapies,” Schatz said. “The future will be a cocktail approach to changing the natural history of the disease.”

The experts interviewed by Endocrine Today encouraged more participation in intervention studies and a focused effort on learning more about the mechanisms behind type 1 diabetes.

In addition, “we need money because large-scale trials are incredibly expensive; we need commitment from the president, who better stop vetoing type 1 diabetes money. We need type 1 diabetes funds to continue. We need enough people to believe this issue is important, and, aside from researchers, we need physicians and clinical endocrinologists to refer patients,” Becker said. “There is no single important thing. We need all of these things and without them we will never find an intervention to prevent type 1 diabetes.” – by Katie Kalvaitis

FDA expands use of Tivicay for HIV-1 in children of lower weight


ViiV Healthcare announced the FDA approved an expansion of the drug label for Tivicay 10 mg and 25 mg oral tablets, reducing the weight limit from at least 40 kg to at least 30 kg, for the treatment of HIV-1 in patients aged 6 to 12 years.

Tivicay (dolutegravir) will be available for use in pediatric patients weighing at least 30 kg living with HIV-1 who are either treatment naive or treatment experienced, provided they have not previously been administered an integrase inhibitor.

“From day 1, children and adolescents have been, and remain, a key focus in our drive to improve outcomes for people living with HIV,” John C. Pottage Jr., MD, chief scientific and medical officer of ViiV Healthcare, said in a press release. “Through our research and development efforts, corporate social responsibility programs, partnerships and access initiatives, we have made a difference for younger populations. This approval by the FDA provides more children and adolescents the option to be treated with dolutegravir in the U.S., and supports the global UNAIDS pediatric treatment target.”

The FDA based its approval on 24-week data from the phase 1/2 multicenter, open-label P1093 safety and efficacy study of dolutegravir plus optimized background regimen among children and adolescents infected with HIV-1 in age defined cohorts.

Study results demonstrated that treatment with dolutegravir plus an optimized background regimen was generally well-tolerated and provided efficacy through to week 24 in HIV-1 infected children and adolescents aged 6 to 12 years weighing at least 30 kg.

The most common adverse events associated with the use of dolutegravir among adults included insomnia (3%), fatigue (2%) and headache (2%). According to study results, grade 2 adverse events reported by more than one patient were decreased neutrophil count (n = 3) and diarrhea (n = 2); no grade 3 or 4 drug-related adverse events were reported, and no adverse events caused discontinuation of the drug regimen.

ViiV Healthcare reported that its ongoing P1093 study will continue to evaluate dolutegravir in pediatric populations down to age 4 weeks, weighing at least 3 kg.

Bionic pancreas effective in home setting for reducing glucose, hypoglycemia


Use of a bionic pancreas was associated with reductions in mean glucose and hypoglycemia compared with conventional insulin pump therapy, when used in the home setting by adults with type 1 diabetes.

“This was our first true home-study,” Edward R. Damiano, PhD, professor of biomedical engineering at Boston University, said during a presentation at the American Diabetes Association Scientific Sessions. “All participants lived at home and went to work, and there were no restrictions on diet or exercise.”

Edward Damiano

Edward R. Damiano

Damiano and colleagues sought to determine the efficacy of continuous, multi-day, automated glycemic control using a bihormonal bionic pancreascompared with conventional insulin pump therapy in adults with type 1 diabetes living at home and performing normal activities. Glycemic regulation was compared between the bionic pancreas and insulin pump over 11 days each in all participants. During the bionic pancreas period, continuous glucose monitor (CGM) data were used by an autonomous adaptive algorithm to control subcutaneous insulin and glucagon delivery. During the pump period, patients managed their own conventional insulin pump therapy.

The mean reduction in glucose level was 162 mg/dL with the bionic pancreas compared with 141 mg/dL with the insulin pump (P < .0001). The bionic pancreas was also associated with greater reductions in time less than 60 mg/dL by CGM (1.9% vs. 0.6%; P < .0001).

In other results, the mean number of symptomatic hypoglycemia events was lower with the bionic pancreas: 0.59 events per day compared with 0.6 events per day (P = .023). The mean total daily dose of insulin was 6% greater with the bionic pancreas compared with the insulin pump (P = .01). – by Amber Cox

Sense of urgency needed to combat ‘invisible disease’ of diabetes


Diabetes is a misunderstood and largely ignored health epidemic, one that threatens to grow larger and claim more lives around the world, Desmond Schatz, MD, said during a presentation at the American Diabetes Association Scientific Sessions.

“A patient dies every 6 seconds from diabetes and its consequences, and it is projected that 1 in 10 will live with diabetes by the year 2040, with health care expenses over the next 2 decades expected to exceed 7 trillion dollars,” Schatz, president of medicine and science for the ADA, said during his address.

Schatz, who is also associate director of the Clinical Research Center in the department of pediatrics at the University of Florida, said advocacy for diabetes must be turned up to 212 degrees — the boiling point of water — to create a “scalding sense of urgency” to transition the disease to a highly-visible crisis that “threatens the very fabric and resources of our society.”

According to Schatz, “diabetes is the global warming of health care: another calamity that has conspicuously been ignored while HIV/AIDS and the Zika virus and other diseases and epidemics grab the spotlight. Patients have a right to demand a fiery sense of urgency of now.”

The reality, he said, is that health care providers are largely invisible to patients, who often manage a very complex disease on their own.

“How many type 2 [diabetes] patients choose to be invisible to us, largely because of their own sense of failure and frustration they confront during an office visit?” Schatz said. “It’s easy to criticize and cajole these patients in the hopes of improving their clinical profiles, but how often do we actually take the time to hear or learn about their burden, and the real reasons they why can’t seem to control their disease?

“Diabetes is like a wildfire, raging through this country and across the globe, but is anybody really paying attention?” Schatz said. “Every year we hear similar statistics, yet the disease and the related skyrocketing health care costs seem invisible to the governments of the world.”

The general public, too, remain in the dark about diabetes, Schatz said, typically perceiving cancer and heart disease to be far more serious than diabetes.

“The vast majority of the public polled feel that people with diabetes have themselves to blame, and know very little about the disease,” Schatz said.

Citing NIH funding data, Schatz noted a disparity in funding between diabetes research and funding for cancer and HIV/AIDS: $34.71 per person spent on diabetes research, vs. more than $2,500 per person for HIV/AIDS research.

“What can we, the diabetes community, learn from the HIV/AIDS movement?” Schatz said. “The origin began with an army of advocates who created a sense of urgency and achieved transformational change in a few decades.”

Advocates must do more than talk, he said. They must make demands, for better treatments, better reimbursement policies, and an end to discrimination in both schools and work places, while also demanding more education and support from multidisciplinary teams, and create an awareness campaign to help make the disease of diabetes a visible one.

“We need to push that urgency button by asking the bigger and more personally confrontational questions, like, why aren’t we further along? Why have we not yet found a cure? Is there something more that we need to be doing?” Schatz said. “We need to think outside the box. We need to better share our data and remove the barriers to collaboration … the single biggest component of innovation.

“Each of us should ask ourselves: What have we done today, and what will we do tomorrow to act up, to speak out and to demand action?” Schatz said. – by Regina Schaffer