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Summary: Background: Closed-loop insulin delivery systems have the potential to address suboptimal glucose control in children and adolescents with type 1 diabetes. We compared safety and efficacy of the Cambridge hybrid closed-loop algorithm with usual care over 6 months in this population. Methods: In a multicentre, multinational, parallel randomised controlled trial, participants aged 6–18 years using insulin pump therapy were recruited at seven UK and five US paediatric diabetes centres. Key inclusion criteria were diagnosis of type 1 diabetes for at least 12 months, insulin pump therapy for at least 3 months, and screening HbA1c levels between 53 and 86 mmol/mol (7·0–10·0%). Using block randomisation and central randomisation software, we randomly assigned participants to either closed-loop insulin delivery (closed-loop group) or to usual care with insulin pump therapy (control group) for 6 months. Randomisation was stratified at each centre by local baseline HbA1c. The Cambridge closed-loop algorithm running on a smartphone was used with either (1) a modified Medtronic 640G pump, Medtronic Guardian 3 sensor, and Medtronic prototype phone enclosure (FlorenceM configuration), or (2) a Sooil Dana RS pump and Dexcom G6 sensor (CamAPS FX configuration). The primary endpoint was change in HbA1c at 6 months combining data from both configurations. The primary analysis was done in all randomised patients (intention to treat). Trial registration ClinicalTrials.gov, NCT02925299. Findings: Of 147 people initially screened, 133 participants (mean age 13·0 years [SD 2·8]; 57% female, 43% male) were randomly assigned to either the closed-loop group (n=65) or the control group (n=68). Mean baseline HbA1c was 8·2% (SD 0·7) in the closed-loop group and 8·3% (0·7) in the control group. At 6 months, HbA1c was lower in the closed-loop group than in the control group (between-group difference −3·5 mmol/mol (95% CI −6·5 to −0·5 [–0·32 percentage points, −0·59 to −0·04]; p=0·023). Closed-loop usage was low with FlorenceM due to failing phone enclosures (median 40% [IQR 26–53]), but consistently high with CamAPS FX (93% [88–96]), impacting efficacy. A total of 155 adverse events occurred after randomisation (67 in the closed-loop group, 88 in the control group), including seven severe hypoglycaemia events (four in the closed-loop group, three in the control group), two diabetic ketoacidosis events (both in the closed-loop group), and two non-treatment-related serious adverse events. There were 23 reportable hyperglycaemia events (11 in the closed-loop group, 12 in the control group), which did not meet criteria for diabetic ketoacidosis. Interpretation: The Cambridge hybrid closed-loop algorithm had an acceptable safety profile, and improved glycaemic control in children and adolescents with type 1 diabetes. To ensure optimal efficacy of the closed-loop system, usage needs to be consistently high, as demonstrated with CamAPS FX. Funding: National Institute of Diabetes and Digestive and Kidney Diseases.

Objectives: Pectus excavatum, or funnel chest, causes both physical and psychosocial issues, affecting health-related quality of life. However, the literature on how funnel chest affects daily living prior to corrective surgery is sparse. Therefore, the study aimed to describe the experiences of living with funnel chest prior to correctional surgery., Materials and Methods: The study had a qualitative exploratory design. Consecutive sampling was applied in which all individuals from a single cardiothoracic department scheduled for the minimally invasive repair of pectus excavatum were asked to participate. Nineteen participants, 17 men and two women, participated in the study. Individual telephone interviews were conducted from February 2020 until April 2021. The interviews were analyzed with qualitative content analysis using an inductive approach., Results: The overall theme "To have or not to have a cavity in my chest, it could make a difference" was interpreted as the latent meaning of the participants' experiences. The theme included two subthemes with three categories each. The subtheme "The funnel chest puts a weight on my shoulders" describes the heavy burden the funnel chest places on the participants. The second subtheme, "This is me, but I want to change my future", describes that participants see the funnel chest as a part of themselves; nevertheless, they look forward to surgery and a life without it., Conclusion: The results emphasize the heavy burden funnel chest causes and the great limitations it places on the individual. It also highlights the importance of surgery and the hope for a better future for individuals with funnel chest., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Norlander et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To report the safety and side effects associated with taking verapamil for beta-cell preservation in children with newly-diagnosed T1D., Research Design and Methods: Eighty-eight participants aged 8.5 to 17.9 years weighing ≥ 30 kg were randomly assigned to verapamil (N = 47) or placebo (N = 41) within 31 days of T1D diagnosis and followed for 12 months from diagnosis, main CLVer study. Drug dosing was weight-based with incremental increases to full dosage. Side effect monitoring included serial measurements of pulse, blood pressure, liver enzymes, and electrocardiograms (ECGs). At study end, participants were enrolled in an observational extension study (CLVerEx), which is ongoing. No study drug is provided during the extension, but participants may use verapamil if prescribed by their diabetes care team., Results: Overall rates of adverse events were low and comparable between verapamil and placebo groups. There was no difference in the frequency of liver function abnormalities. Three CLVer participants reduced or discontinued medication due to asymptomatic ECG changes. One CLVerEx participant (18 years old), treated with placebo during CLVer, who had not had a monitoring ECG, experienced complete AV block with a severe hypotensive episode 6 weeks after reaching his maximum verapamil dose following an inadvertent double dose on the day of the event., Conclusions: The use of verapamil in youth newly-diagnosed with T1D appears generally safe and well tolerated with appropriate monitoring. We strongly recommend monitoring for potential side effects including an ECG at screening and an additional ECG once full dosage is reached.ClinicalTrials.gov number: NCT04233034., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Ekhlaspour receives salary support from NIH and research support from JDRF. She reports receiving consulting fees from Medtronic, Tandem Diabetes Care and Ypsomed; receiving speaking fees from Insulet; and receiving research support from Medtronic, MannKind and Abbot through her institution. Her prior institution has received research support from Medtronic, Tandem Diabetes Care, Insulet, Dexcom and Beta Bionics. Dr. Buckingham reports receiving grants, personal fees, and/or nonfinancial support from Medtronic, Tandem Diabetes Care, Insulet, NovoNordisk, and Lilly and reports his institution has received research funding from Medtronic, Tandem Diabetes Care, Beta Bionics, and Insulet. Dr. Bauza reports no disclosures. Dr. Clements reports receiving personal fees from Glooko Inc and nonfinancial support from Dexcom and Abbott Diabetes Care. Dr. Forlenza reports serving as a consultant, speaker or advisory board member for Medtronic, Dexcom, Abbott, Tandem Diabetes Care, Insulet, Lilly, and Beta Bionics and reports his institution has received funding on his behalf for research grants from Medtronic, Dexcom, Abbott, Tandem Diabetes Care, Insulet, Lilly, and Beta Bionics. Dr. Neyman reports no disclosures. Dr. Norlander reports no disclosures. Dr. Schamberger reports no disclosures. Dr. Sherr reported receiving speaking honoraria from Lilly, Insulet, Medtronic, and Zealand Pharma; serving on advisory boards for Bigfoot Biomedical, Cecelia Health, Insulet, Medtronic Diabetes, JDRF (formally the Juvenile Diabetes Research Foundation) T1D Fund, StartUp Health T1D Moonshot, and Vertex Pharmaceuticals; receiving consultant fees from Insulet and Medtronic; and reported that her institution has received research grant support from Medtronic and Insulet. Mr. Bailey reports no disclosures. Dr. Beck reports his institution has received funding on his behalf as follows: grant funding and study supplies from Tandem Diabetes Care, Beta Bionics, and Dexcom; grant funding from Bigfoot Biomedical; study supplies from Medtronic, Ascencia, and Roche; consulting fees and study supplies from Lilly and NovoNordisk; and consulting fees from Insulet and Zucara Therapeutics. Dr. Kollman reports receiving grants from Dexcom and Tandem Diabetes Care. Ms. Beasley reports no disclosures. Dr. Cobry reports no disclosures. Dr. DiMeglio reports receiving consulting or advisory fees from Abata Therapeutics, MannKind, Provention Bio, and Zealand Pharma and study supplies from Dexcom. Dr. Paprocki reports no disclosures. Dr. Van Name reports receiving research support from ProventionBio. Dr. Moran reports serving on advisory boards from Dompé Farmaceutici SpA, ProventionBio, and Abata Therapeutics; serving on a data and safety monitoring board for NovoNordisk; and reported that her institution has received grant funding on her behalf from Abbott Diabetes, ProventionBio, Intrexon (now Precigen), and Caladrius Biosciences and study supplies from NovoNordisk, Medtronic, and Abbott Diabetes., (© 2024 The Authors.)

Objectives: Pectus excavatum (PE) can cause both physical and psychosocial symptoms and affect patients' health-related quality of life. Previous international studies have shown that the Nuss procedure increases both self-esteem and body image. The aim of the study was to evaluate the health-related quality of life in patients who have undergone the Nuss procedure for PE., Methods: The study had a cross-sectional multicentre design. All patients (N = 420) who underwent the Nuss procedure for PE in 3 cardiothoracic departments in Sweden from 2000 to 2019 were invited to answer the RAND-36 and Nuss Questionnaire modified for adults. Genders were compared using the Mann-Whitney U-test. Patients were divided into groups based on age at time of surgery (<20, 20-30 or >30 years) and analysed by the Kruskal-Wallis H-test with post-hoc analyses., Results: A total of 236 patients returned the questionnaires; 82.2% were males. Men scored significantly better on the modified Nuss Questionnaire total (P = 0.01) and psychosocial (P = 0.02) subscales. Patients who had surgery at <20 years of age had significantly better scores on the same scales (P = 0.007 and 0.006, respectively) compared to patients aged 20-30 years at the time of surgery. However, no significant difference was seen in comparison with patients >30 years. Patients who had their bar removed had significantly better values on both scales., Conclusions: Male gender, young age at surgery and bar removal seem to be associated with better health-related quality of life after the Nuss procedure for PE., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Objective: Achieving optimal glycemic control for many individuals with type 1 diabetes (T1D) remains challenging, even with the advent of newer management tools, including continuous glucose monitoring (CGM). Modern management of T1D generates a wealth of data; however, use of these data to optimize glycemic control remains limited. We evaluated the impact of a CGM-based decision support system (DSS) in patients with T1D using multiple daily injections (MDI)., Research Design and Methods: The studied DSS included real-time dosing advice and retrospective therapy optimization. Adults and adolescents (age >15 years) with T1D using MDI were enrolled at three sites in a 14-week randomized controlled trial of MDI + CGM + DSS versus MDI + CGM. All participants (N = 80) used degludec basal insulin and Dexcom G5 CGM. CGM-based and patient-reported outcomes were analyzed. Within the DSS group, ad hoc analysis further contrasted active versus nonactive DSS users., Results: No significant differences were detected between experimental and control groups (e.g., time in range [TIR] +3.3% with CGM vs. +4.4% with DSS). Participants in both groups reported lower HbA1c (-0.3%; P = 0.001) with respect to baseline. While TIR may have improved in both groups, it was statistically significant only for DSS; the same was apparent for time spent <60 mg/dL. Active versus nonactive DSS users showed lower risk of and exposure to hypoglycemia with system use., Conclusions: Our DSS seems to be a feasible option for individuals using MDI, although the glycemic benefits associated with use need to be further investigated. System design, therapy requirements, and target population should be further refined prior to use in clinical care., (© 2021 by the American Diabetes Association.)

Background: Glycemic control is particularly challenging for toddlers and preschoolers with type 1 diabetes (T1D), and data on the use of closed-loop systems in this age range are limited. Materials and Methods: We studied use of a modified investigational version of the Tandem t:slim X2 Control-IQ system in children aged 2 to 5 years during 48 h in an outpatient supervised hotel (SH) setting followed by 3 days of home use to examine the safety of this system in young children. Meals and snacks were not restricted and boluses were estimated per parents' usual routine. At least 30 min of daily exercise was required during the SH phase. All participants were remotely monitored by study staff while on closed-loop in addition to monitoring by at least one parent throughout the study. Results: Twelve participants diagnosed with T1D for at least 3 months with mean age 4.7 ± 1.0 years (range 2.0-5.8 years) and hemoglobin A1c of 7.3% ± 0.8% were enrolled at three sites. With use of Control-IQ, the percentage of participants meeting our prespecified goals of less than 6% time below 70 mg/dL and less than 40% time above 180 mg/dL increased from 33% to 83%. Control-IQ use significantly improved percent time in range (70-180 mg/dL) compared to baseline (71.3 ± 12.5 vs. 63.7 ± 15.1, P  = 0.016). All participants completed the study with no adverse events. Conclusions: In this brief pilot study, use of the modified Control-IQ system was safe in 2-5-year-old children with T1D and improved glycemic control.

Background: Pectus excavatum (PE) is the most common congenital chest wall deformity. Most individuals with PE suffer from psychosocial problems, with low self-esteem and poor body image. Correctional surgery for PE is available, the most widely used is the Nuss procedure. The Nuss procedure has previously been reported to improve self-esteem, body image and health-related quality of life (HRQoL). To assess HRQoL among individuals with PE, the Nuss Questionnaire modified for Adults (NQ-mA) and Single Step Questionnaire (SSQ) has been developed. The aim of the current study was to translate and culturally adapt NQ-mA and SSQ to fit a Swedish context, and to evaluate the psychometric properties, and validate the culturally adapted versions., Methods: Individuals who had undergone the Nuss procedure for pectus excavatum were invited to participate in a multicentre study with cross-sectional design. HRQoL was assessed by NQ-mA, SSQ and RAND-36. Psychometric properties for NQ-mA and SSQ were evaluated by content validity index and construct validity (exploratory factor analysis, confirmatory factor analysis, and inter-scale correlations). Known-groups validity, as well as floor and ceiling effects, were evaluated. Internal consistency reliability was examined using Cronbach's alpha., Results: In total 236 individuals participated in the study. Content validity index for NQ-mA showed satisfactory results, except for two items. Factor analysis for NQ-mA suggested a two-factor model, with exclusion of two items. Subscales correlated adequately with RAND-36's domains. Known-groups validity for NQ-mA demonstrated high sensitivity for between-group differences. Ceiling effects were present in several items. Cronbach's alpha for NQ-mA was .89. Confirmatory factor analysis for SSQ resulted in a three-factor model, with exclusion of five items. However, this model was shown to be unstable through further exploratory factor analysis testing, and no further psychometric tests were conducted for SSQ., Conclusion: The 10-item Swedish version of NQ-mA was shown to be valid for research and clinical assessment of HRQoL in individuals with pectus excavatum. The Swedish version of SSQ requires revision of items before further validation can be performed.

Objective: The primary objective of this trial was to evaluate the feasibility, safety, and efficacy of a predictive hyperglycemia and hypoglycemia minimization (PHHM) system vs predictive low glucose suspension (PLGS) alone in optimizing overnight glucose control in children 6 to 14 years old., Research Design and Methods: Twenty-eight participants 6 to 14 years old with T1D duration ≥1 year with daily insulin therapy ≥12 months and on insulin pump therapy for ≥6 months were randomized per night into PHHM mode or PLGS-only mode for 42 nights. The primary outcome was percentage of time in sensor-measured range 70 to 180 mg/dL in the overnight period., Results: The addition of automated insulin delivery with PHHM increased time in target range (70-180 mg/dL) from 66 ± 11% during PLGS nights to 76 ± 9% during PHHM nights (P<.001), without increasing hypoglycemia as measured by time below various thresholds. Average morning blood glucose improved from 176 ± 28 mg/dL following PLGS nights to 154 ± 19 mg/dL following PHHM nights (P<.001)., Conclusions: The PHHM system was effective in optimizing overnight glycemic control, significantly increasing time in range, lowering mean glucose, and decreasing glycemic variability compared to PLGS alone in children 6 to 14 years old., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The safety and effectiveness of a continuous, day-and-night automated glycaemic control system using insulin and glucagon has not been shown in a free-living, home-use setting. We aimed to assess whether bihormonal bionic pancreas initialised only with body mass can safely reduce mean glycaemia and hypoglycaemia in adults with type 1 diabetes who were living at home and participating in their normal daily routines without restrictions on diet or physical activity., Methods: We did a random-order crossover study in volunteers at least 18 years old who had type 1 diabetes and lived within a 30 min drive of four sites in the USA. Participants were randomly assigned (1:1) in blocks of two using sequentially numbered sealed envelopes to glycaemic regulation with a bihormonal bionic pancreas or usual care (conventional or sensor-augmented insulin pump therapy) first, followed by the opposite intervention. Both study periods were 11 days in length, during which time participants continued all normal activities, including athletics and driving. The bionic pancreas was initialised with only the participant's body mass. Autonomously adaptive dosing algorithms used data from a continuous glucose monitor to control subcutaneous delivery of insulin and glucagon. The coprimary outcomes were the mean glucose concentration and time with continuous glucose monitoring (CGM) glucose concentration less than 3·3 mmol/L, analysed over days 2-11 in participants who completed both periods of the study. This trial is registered with ClinicalTrials.gov, number NCT02092220., Findings: We randomly assigned 43 participants between May 6, 2014, and July 3, 2015, 39 of whom completed the study: 20 who were assigned to bionic pancreas first and 19 who were assigned to the comparator first. The mean CGM glucose concentration was 7·8 mmol/L (SD 0·6) in the bionic pancreas period versus 9·0 mmol/L (1·6) in the comparator period (difference 1·1 mmol/L, 95% CI 0·7-1·6; p<0·0001), and the mean time with CGM glucose concentration less than 3·3 mmol/L was 0·6% (0·6) in the bionic pancreas period versus 1·9% (1·7) in the comparator period (difference 1·3%, 95% CI 0·8-1·8; p<0·0001). The mean nausea score on the Visual Analogue Scale (score 0-10) was greater during the bionic pancreas period (0·52 [SD 0·83]) than in the comparator period (0·05 [0·17]; difference 0·47, 95% CI 0·21-0·73; p=0·0024). Body mass and laboratory parameters did not differ between periods. There were no serious or unexpected adverse events in the bionic pancreas period of the study., Interpretation: Relative to conventional and sensor-augmented insulin pump therapy, the bihormonal bionic pancreas, initialised only with participant weight, was able to achieve superior glycaemic regulation without the need for carbohydrate counting. Larger and longer studies are needed to establish the long-term benefits and risks of automated glycaemic management with a bihormonal bionic pancreas., Funding: National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, and National Center for Advancing Translational Sciences., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

There is a large concern in the society today about the threat posed from releases of chemical, biological, radiological or nuclear (CBRN) materials, whether accidental or malicious. A rapid and adapted response to a CBRN incident combined with a thorough public communication is believed to decrease the detrimental impacts on health and to reduce the psychosocial effects. To facilitate CBRN exercises, which often can be regarded by non-specialists as rather complicated, a tool in the form of a set of Exercise cards for CBRN emergency response table-top exercises has been developed. The exercise tool is a generic tool intended for an exercise director and consists of a set of adaptable scenarios with supporting instructions and questions that deal with preparedness, acute response and mitigation efforts. The exercise tool was tested in three different settings with positive results and has been assessed to be a cost-efficient means to train and test public health response to CBRN incidents., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Innovative approaches to improving end-of-life care are needed. One strategy involves government/community partnerships to improve care., Objective: Engage health care provider and health care consumer communities in the State of Minnesota to improve end-of-life care., Design: The Minnesota Commission on End of Life Care was formed to make recommendations that would be used by public and private policy makers to improve care in the state., Results: An innovative selection process brought together a broad group of people to identify, prioritize, and make recommendations regarding end-of-life care in the state. Carefully selected leadership, good planning, and organization ensured a successful process that kept all appointed commission members engaged throughout the 18-month project. Using a consensus process, the Commission endorsed a framework for end-of-life care and made specific recommendations for improving access, education and public policy. This paper describes the process of developing and implementing the Commission, the challenges, successes, and lessons learned.

Objective: To determine whether home health agency patients' preferences to die at home can be honored following a structured, professionally facilitated advance-care planning (ACP) process provided in the home., Design: A case series of patients who were identified by their home health agency nurses as having a life-limiting illness and then referred for social service assessment, followed for at least 6 months, with median follow-up of 191 days., Setting: A large, urban, home health agency owned by a not-for-profit integrated healthcare system., Participants: Eighty-four adult patients (median age 75, range 37-94) receiving home care services other than hospice., Intervention: Formally structured social work visits at patients' homes to discuss end-of-life issues, with communication of results to home health nurses and attending physicians. Social workers performed standard psychosocial assessments, obtained patient and family preferences regarding end-of-life care, and provided education about hospice services., Measurements: Acceptance of the ACP process, preferences for location of end-of-life care, location of care at the end of life, adequacy of timing of intervention as measured by length of life after ACP, and use of hospice services., Results: Eighty-three of 84 participants (99%) were willing to complete an ACP process in the home setting. Of the 54 patients expressing a clear preference for location of end-of-life care, 46 (82%) wanted this care to be at home. Thirty-nine (46%) of the participants died within 90 days of ACP; 58 (69%) died by the end of the study. Forty-three (75%) of these deaths occurred at home or in a hospice residence. Fifty-one (61%) patients used home, residential, or nursing home-based hospice services during the study., Conclusion: In this series of seriously ill home health patients, most preferred to die at home and virtually all were willing to participate in a home-based ACP process. Facilitating ACP among such patients and their families was associated with end-of-life care at home. Use of hospice services was common following ACP in this population.

As Yogi Berra once said, "The future ain't what it used to be." In the era of rapid change in health care, hospice and palliative care programs will survive only through organizational teamwork. Using the lessons of baseball, we present a stadium-eye perspective on how programs can take the three fundamentals of baseball--pitching, batting, and fielding--and translate them into the three fundamentals of organizational teamwork--clinical, operational, and financial. The best clinicians (pitchers) are of no use if the office operations (batting) keep the patients (fans) out of the stadium and no program can survive without the financial resources (fielding.) When you come to a fork in the road, take it.

Home care and hospice nurses are uniquely positioned to facilitate early discussions about patient's care wishes and goals at the end of life. This article presents a definition of advance care planning, why it is important, a model for facilitating the discussion, suggestions for overcoming barriers, and tools to assist nurses in feeling more comfortable integrating the subject into daily practice.

Although suffering is frequently encountered in the hospice setting, few studies examine this condition. The purpose of this study was to examine the relationship between terminally ill hospice patients' pain and their physical, spiritual, and personal or family suffering. Using a tool developed to measure suffering in those categories, a convenience sample of 92 patients were asked to rate their worst pain within the last 24 hours, and to rate their suffering at the time of the interview. All items were rated on a 0-10 Numeric Intensity Scale. Pain scores and suffering scores were divided into four categories; no pain or no suffering (0), mild pain or mild suffering (1-3), moderate pain or moderate suffering (4-6), and severe pain or severe suffering (7-10). Mean scores were compared for pain and suffering. More patients experienced suffering than pain. The highest mean suffering scores occurred in the severe pain category. Correlation coefficients for each suffering and pain category were also calculated. Results indicated a statistically significant correlation only between severe pain and suffering in the categories of loss of enjoyment of life, unfinished business, and concern for loved ones. Data indicated that patients view pain and suffering as separate entities. Further research is needed to better define the relationship between pain and suffering in order to improve assessment and intervention in a hospice setting.

The lungs are a port of entry and primary infectious focus of Coxiella burnetii, the obligate intracellular contagium of the worldwide zoonosis Q fever. The infectious process and immune response are characterised by studies in cell culture and animal systems. Following endocytosis, replication exclusively occurs in the phagolysosome. Several potential virulence factors are described.

Serologically verified indigenous Q fever is described in a 52-y-old male, who presented with persistent fever, muscle and joint pain, headache and non-purulent cough. Institution of doxycycline resulted in prompt recovery. Coxiella burnetii was isolated from mouldy hay in a barn. The strain differs from previously isolated ones in Sweden.

Q-fever is caused by Coxiella burnetii, which is an obligate intracellular bacterium with a broad spectrum of host cells, including macrophages. Cytokines produced from macrophages infected by intracellular bacteria play a critical role in the expression of innate immune responses as well as in the subsequent triggering of protective acquired cell-mediated immunity. We followed the induction and secretion of the pro-inflammatory cytokines interleukin 1 alpha (IL-1alpha), tumor necrosis factor alpha (TNF-alpha), and interleukin 12 (IL-12) in the macrophage-like mouse cell line P388D1 during the initial phase of an in vitro infection by virulent C. burnetii Nine Mile. Secretion of IL-1alpha and TNF-alpha were observed within 3 h post-inoculation. IL-12, however, was not detected in cell supernatants. Two forms of C. burnetii exist, virulent phase I and avirulent phase II organisms. To determine whether the cytokine response was dependent on the form of C. burnetii, the induction of IL-1alpha and TNF-alpha in infected P388D1 cells was compared. Both cytokines were produced by macrophages early after infection with Phase I bacteria. A similar induction of TNF-alpha was observed after infection with the avirulent Phase II bacteria, but no IL-1alpha induction could be detected. As the only difference identified between the two forms of C. burnetii is the composition of their lipopolysaccharides (LPS), the ability of each of the purified LPS from the two variants to induce IL-1alpha was investigated. Purified C. burnetii LPS induced a moderate IL-1alpha response in comparison to that induced by the efficient stimulator E. coli LPS. Furthermore, there was no significant difference in action between Phase I and Phase II LPS preparations. We thus postulate that factors other than LPS differ between the two variants of C. burnetii, and these differences may account for differences in IL-1alpha induction.