Medicine Correspondence Blog
The Medicine Correspondence Blog allows authors to post Letters to the Editors, Reviews, and other editorial writings that are not considered original research.

Thursday, July 13, 2017

Chaara and colleagues have to be commended for rescuing a patient with severe aortic stenosis suffering from cardiac arrest by means of balloon aortic valvuloplasty and intracardiac adrenaline between others1. During resuscitation, manual or automatic massage would probably lead to minimal arterial pressure and output, assessed by low end tidal carbon dioxide (EtCO2), due to obstruction to flow by the diseased aortic valve. Such resuscitation efforts may be vain without treatment of severe aortic stenosis and prognosis may remain dismal even with balloon aortic valvuloplasty attempts in such severe patients. We would like to temper this dismal prognosis by reporting another favorable outcome.

An 87-year old female patient was planned for Trans catheter Aortic Valve Replacement for severe and symptomatic aortic stenosis. The procedure began without intubation by femoral access but circulatory collapse occurred, immediately followed by cardiac arrest. Urgent balloon aortic valvuloplasty, along with adrenaline (50 mg), intubation, defibrillation (6 shocks) allowed an improvement of hemodynamics (Et CO2 from 14 to 37 mmHg) after 45 minutes. Afterward, Trans catheter Aortic Valve Replacement was performed with success. After temporary trans venous pacing leads retrieval, tamponade occurred that necessitated immediate percutaneous drainage. It was hypothesized that external chest compressions may have induced right ventricular perforation. Patient was extubated the second day, recovered without neurological sequel (cerebral performance category 1) and regained her home on the seventh day.

Moreover, we noted that Chaara's patient had ST segment depression despite no obstructive coronary artery. This may be illustrated by the left ventricular pressure curves that can allow calculation of coronary perfusion pressure (end diastolic arterial pressure minus end diastolic ventricular pressure). In their patient, coronary perfusion pressure was null during arrest and very low (<30 mmHg) at recovery.

To conclude, we emphasize the role of balloon aortic valvuloplasty during cardiac arrest complicating severe aortic stenosis to improve the efficacy of resuscitation efforts that may not be vain.


Acknowledgement : Drs Joseph Anconina, Fouad El Buhali, and Huy Long Doan who took care of the patient. 

Sébastien Champion, MD; Grégoire Dambrin, MD

Réanimation, clinique de Parly 2, Ramsay Générale de Santé, 21 rue Moxouris, 78150 Le Chesnay, France.

Corresponding author : Sébastien Cchampion, 27 rue Lafayette, 78000 Versailles, France;

Financial Disclosures: None

Conflicts of Interest: NONE

List of abbreviations: EtCO2: end tidal carbon dioxide 


1.         Chaara J, Meier P, Ellenberger C, et al. Percutaneous Aortic Balloon Valvuloplasty and Intracardiac Adrenaline in Electromechanical Dissociation as Bridge to Transcatheter Aortic Valve Implantation. Medicine (Baltimore) 2015;94(26):e1061. 

Thursday, July 13, 2017

 I have read with interest the study entitled "Is combined topical and intravenous tranexamic acid superior to intravenous tranexamic acid alone for controlling blood loss after total hip arthroplasty?" This is a relevant question as the optimal administration route of tranexamic acid is still controversial in terms of the efficiency and safety in total hip arthroplasty (THA). Therefore, as surgeons, we wonder whether combined use is more effective than intravenous only to reduce the need for transfusion or total blood loss without increased risk of complications. We acknowledge the authors' work, as a valuable contribution to this discussion; however, I would like to point out critical error in the inclusion methodology of their research.

The authors stated that their methodology would only include randomized controlled trials. But we have found that the study included data from a retrospective observational study (Machin 2014) which should be excluded from the analysis. We also found that one other study (Wu 2016) was the results from a revision THA not primary THA. What is also worth mentioning is that the population of patients included in the studies with a comprehensive error accounts for 21.6 % (n = 184) of the total patient population involved in this meta-analysis. I have tried to perform sensitivity analysis by comparing the overall results with the results excluding these two studies but could not because four papers were written in Chinese were difficult to translate.

 Meta-analyses of randomized controlled trials can be the background for practicing surgeons when deciding which treatment is the best option for the patient. Meta-analysis is based on a systematic and reproducible approach to eliminate subjectivity and objectivity, unlike systematic reviews where there is a risk of prejudice due to the fact that existing research results present conclusions based on subjective judgment of the researcher. Meta-analysis, however, will maximize strength only through the application of rigorous methodologies.

 The research that is carried out by meta-analysis is easier to conduct than other research methods that will be performed in many institutions, or countries without much infrastructure because there is no need to invest the time and effort to collect patient data. In 2016, more than ten meta-analyses regarding the effectiveness and safety of tranexamic acid in joint arthroplasty have been published. [1-10] However this quantitative increase strongly question the quality of this meta-analysis and a careful evaluation is required even though the published journal articles have not yet been evaluated in depth by many journals. [11,12]

 In summary, the results of this study show relevant results through meta-analysis, but have limitations of not applying the inclusion criteria properly.

Corresponding Author

Byung-Ho Yoon, M.D.

Department of Orthopaedic Surgery 

Inje University College of Medicine, Seoul Paik Hospital, Seoul, Korea


1. Shang J, Wang H, Zheng B, Rui M, Wang Y (2016) Combined intravenous and topical tranexamic acid versus intravenous use alone in primary total knee and hip arthroplasty: A meta-analysis of randomized controlled trials. Int J Surg 36 (Pt A):324-329.

2. Zhang XQ, Ni J, Ge WH (2017) Combined use of intravenous and topical versus intravenous tranexamic acid in primary total joint arthroplasty: A meta-analysis of randomized controlled trials. Int J Surg 38:15-20.

3. Chen Y, Chen Z, Cui S, Li Z, Yuan Z (2016) Topical versus systemic tranexamic acid after total knee and hip arthroplasty: A meta-analysis of randomized controlled trials. Medicine (Baltimore) 95 (41):e4656.

4. Fu Y, Shi Z, Han B, Ye Y, You T, Jing J, Li J (2016) Comparing efficacy and safety of 2 methods of tranexamic acid administration in reducing blood loss following total knee arthroplasty: A meta-analysis. Medicine (Baltimore) 95 (50):e5583.

5. Li J, Zhang Z, Chen J (2016) Comparison of efficacy and safety of topical versus intravenous tranexamic acid in total hip arthroplasty: A meta-analysis. Medicine (Baltimore) 95 (36):e4689.

6. Lin C, Qi Y, Jie L, Li HB, Zhao XC, Qin L, Jiang XQ, Zhang ZH, Ma L (2016) Is combined topical with intravenous tranexamic acid superior than topical, intravenous tranexamic acid alone and control groups for blood loss controlling after total knee arthroplasty: A meta-analysis. Medicine (Baltimore) 95 (51):e5344.

7. Weng K, Zhang X, Bi Q, Zhao C (2016) The effectiveness and safety of tranexamic acid in bilateral total knee arthroplasty: A meta-analysis. Medicine (Baltimore) 95 (39):e4960.

8. Zhang P, Liang Y, Chen P, Fang Y, He J, Wang J (2016) Intravenous versus topical tranexamic acid in primary total hip replacement: A meta-analysis. Medicine (Baltimore) 95 (50):e5573.

9. Jiang X, Ma XL, Ma JX (2016) Efficiency and Safety of Intravenous Tranexamic Acid in Simultaneous Bilateral Total Knee Arthroplasty: A Systematic Review and Meta-analysis. Orthop Surg 8 (3):285-293.

10. Moskal JT, Capps SG (2016) Meta-analysis of Intravenous Tranexamic Acid in Primary Total Hip Arthroplasty. Orthopedics 39 (5):e883-892.

11. Bhandari M, Morrow F, Kulkarni AV, Tornetta P, 3rd (2001) Meta-analyses in orthopaedic surgery. A systematic review of their methodologies. J Bone Joint Surg Am 83-A (1):15-24.

12. Dijkman BG, Abouali JA, Kooistra BW, Conter HJ, Poolman RW, Kulkarni AV, Tornetta P, 3rd, Bhandari M (2010) Twenty years of meta-analyses in orthopaedic surgery: has quality kept up with quantity? J Bone Joint Surg Am 92 (1):48-57.​

Monday, June 26, 2017

We read with great interest the article by Zhang et al on "tuberculosis associated hemophagocytic lymphohistiocytosis (TB-HLH) presenting as fever of unknown origin" among eight Chinese adults (age range; 23 to 78 years). [1] The hallmark of these cases was as follows: i) female predominance (six among eight), ii) no apparent underlying co-morbidities or immunosuppression, iii) clinical and radiological presentation quite atypical of tuberculosis, and iv) unfavourable outcome despite initiation of antitubercular and/or HLH directed immunosuppressive/immunomodulator therapies (six of eight expired). Among five of eight patients, HLH preceded the TB diagnosis! All eight patients presented with fever, hepatosplenomegaly, and cytopenias; notably anemia and thrombocytopenia; significant liver dysfunction; coagulation abnormalities; nervous system symptoms. Histiocytic hyperplasia and hemophagocytosis were demonstrated in bone marrow examination in all patients.

Hemophagocytic lymphohistiocytosis represents an unusual spectrum of tuberculosis with more than 80 cases reported in the world literature. [1-8] HLH may precede; coexist; or even follow the TB diagnosis which makes it challenging both from diagnostic and therapeutic aspects.  Liver damage, central to the pathophysiology of HLH, limits the usage of frontline hepatotoxic antitubercular drugs (ATT); as well as early usage of HLH specific immunomodulator therapy such as etoposide. Our systematic review on 63 TB associated HLH patients (1975-2014) have reported a higher mortality rate (49%) in these patients; and nearly 67% of patients had disseminated disease at the time of TB diagnosis. [2] Older age (>30 years, P=0.03), presence of underlying co-morbidities (P=0.04), delayed diagnosis and delayed usage/nonusage of ATT (P=0.003) were associated with inferior survival. Use of immunosuppressive/immunomodulator drugs did not alter the outcome in these patients (P=0.35).[2] Though cases reported by Zhang et al had no underlying co-morbidities, six of eight expired despite specific therapy directed against both TB and HLH; and one of the survivors received etoposide.[1] Similarly, Lerolle and colleagues reported unfavourable outcome among 12 TB-HLH patients (10; Mycobacterium tuberculosis, 2; Mycobacterium Avium Intracellulare Complex) who were immunocompromised; had disseminated disease at presentation.[3] Another systematic review by Brito-Zerón et al also reported five patients with rheumatologic/autoimmune diseases to be complicated by TB-HLH. [4] These patients received biological therapy such as anti-TNF agents prior to HLH diagnosis; and the mortality rate was 60% (3 of 5 expired).[4]

From the available literature, it is evident that HLH preceding TB diagnosis, disseminated disease, delay in diagnosis and/or early initiation of ATT; and biochemical abnormalities are unfavourable clinical signs in patients with TB-HLH. When patients present with prolonged fever, organomegaly, and cytopenia (s), it is essential to suspect both tuberculosis and HLH. Early bone marrow studies and the use of techniques such as PCR can avoid delays in diagnosis and improve the survival rates of patients with tuberculosis-associated hemophagocytic lymphohistiocytosis. The critical point which remains unclear is "how early a treating physician should seek a bone marrow examination in a suspected tuberculosis patient with or without cytopenia to get an alert signal from the hematopathologist".


1.      Zhang Y, Liang G, Qin H, et al. Tuberculosis-associated hemophagocytic lymphohistiocytosis with initial presentation of fever of unknown origin in a general hospital: an analysis of 8 clinical cases. Medicine (Baltimore)  2017; 96:e6575.

2.      Padhi S, Ravichandran K, Sahoo J, et al. Hemophagocytic lymphohistiocytosis: an unusual complication in disseminated Mycobacterium tuberculosis. Lung India 2015; 32:593-601.

3.      Lerolle N, Laanani M, Rivière S, et al. Diversity and combinations of infectious agents in 38 adults with an infection-triggered reactive haemophagocytic syndrome: a multicenter study. Clin Microbiol Infect 2016; 22:268. e1-268.e8.

4.      Brito-Zerón P, Bosch X, Pérez-de-Lis M, et al. Infection is the major trigger of hemophagocytic syndrome in adult patients treated with biological therapies. Semin Arthritis Rheum 2016;45:391-9.

5.      Haque WM, Shuvo ME, Rahim MA, et al. Haemophagocytic syndrome in an adult suffering from pyrexia of unknown origin: an uncommon presentation of tuberculosis: a case report. BMC Res Notes 2017; 10:110.

6.      Long B, Cheng L, Lai SP, et al. Tuberculosis-associated hemophagocytic lymphohistiocytosis in an umbilical cord blood transplant recipient. Clin Chim Acta 2017; 468:111-113.

7.      Seo JH, Lee JA, Kim DH, et al. Tuberculosis-associated hemophagocytic lymphohistiocytosis in adolescent diagnosed by polymerase chain reaction. Korean J Pediatr 2016; 59:43-6.

8.      Koulmane Laxminarayana SL, Nagaraju SP, Prabhu Attur R, et al. Hemophagocytic lymphohistiocytosis: an unusual presentation of tuberculosis in hemodialysis patients. Hemodial Int 2015; 19:E16-E19.



  1. Somanath Padhi, M.D.
  2. Jayaprakash Sahoo, M.D., DM.

 Institutional affiliation:

 1Department of Pathology and Laboratory Medicine, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, Odisha, India.

 2Department of Endocrinology and Metabolism, Jawahar Institute of Medical Education and Research (JIPMER), Puducherry, India.

Corresponding Author: Dr Somanath Padhi, Department of Pathology and Laboratory Medicine, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, Odisha, India, 751019. Email:

​Conflict of Interest: None declared.

Financial support: None declared.

Monday, June 26, 2017

In this study, Wang Jinrong et al. (1) the primary objective was to demonstrate safety and effectiveness (changes in arterial blood gases and KMS) of the secretion clearing strategy within the first 2 hours of NPPV. They had as main conclusion that NPPV in combination with a noninvasive strategy to clear respiratory secretions during the first 2 hours may be superior to CMV in the treatment of patients with AECOPD complicated by HE

We have some remarks on this study for practical implications.

1.- The authors propose the use of this technique in patients with abundant secretions, however they not reporting the volume of secretions extracted especially during the first 2 hours of the use of the OPA device. (2). On the other hand, the authors do not report comorbidities associated with the presence of COPD.

It is known that patients with COPD and comorbid bronchiectasis exhibited more daily sputum production and more exacerbations with greater deterioration of their lung function than COPD patients without bronchiectasis (3)

Although the use of an oropharyngeal airway (OPA) helps to establish a patent airway by preventing the tongue from covering the epiglottis. (4) the displacement of secretion from the peripheral airways to more central ones, not necessarily accompanied by elimination in this way

2.- The authors compare their technique of removal of secretion plus NIMV with CMV

We believe that the "Evaluator" is not adequate because of sedation bias in the hemodynamic state and in the level of the sensorium

Other comparators should be evaluated as: a group of participants treated with NPPV alone (i.e., not in combination with OPA-facilitated clearance of secretions) or a group of participants with more fiberbroncoscopia NIMV  (5)

The authors do not report levels of 2 pressure during the first few hours of use of NIMV, nor monitoring of exhaled tidal volumes or leakage during the procedure

We demonstrated (6) that the NIMV is feasible in patients with hypercapnic encephalopathy and pH less than 7.25 to avoid endotracheal intubation after a quick response from the pH and emptying of pCO2 through strategies that will minimize the alveolar hypoventilation

Authors declare no conflict of interest.



  1. Wang J, Cui Z, Liu S, Gao X, Gao P, Shi Y, Guo S, Li P. Early use of noninvasive techniques for clearing respiratory secretions during noninvasive positive-pressure ventilation in patients with acute exacerbation of chronic obstructive pulmonary disease and hypercapnic encephalopathy: A prospective cohort study. Medicine (Baltimore). 2017 Mar; 96 (12):e6371. doi: 10.1097/MD.0000000000006371.
  2. Chicayban LM, Zin WA, Guimarães FS. Can the Flutter Valve improve respiratory mechanics and sputum production in mechanically ventilated patients? A randomized crossover trial. Heart Lung. 2011: 40:545-53
  3. Ni Y, Shi G,  Yu Y, Hao J, Chen T, Song H. Clinical characteristics of patients with chronic obstructive pulmonary disease with comorbid bronchiectasis: a systemic review and meta-analysis. Int J Chron Obstruct Pulmon Dis. 2015; 28;10:1465-1475.
  4. Takahashi S, Ono T, Ishiwata Y, Kuroda T. Effect of changes in the breathing mode and body position on tongue pressure with respiratory-related oscillations. Am J Orthod Dentofacial Orthop 1999; 115:239-246.
  5. Da Conceiçao M, Genco G, Favier JC, Bidallier I, Pitti R. [Fiberoptic bronchoscopy during noninvasive positive-pressure ventilation in patients with chronic obstructive lung disease with hypoxemia and hypercapnia]. Ann Fr Anesth Reanim. 2000: 19:231-236.
  6. Briones Claudett KH, Briones Claudett M, Chung Sang Wong M, Nuques Martinez A, Soto Espinoza R, Montalvo M, Esquinas Rodriguez A, Gonzalez Diaz G, Grunauer Andrade M. Noninvasive mechanical ventilation with average volume assured pressure support (AVAPS) in patients with chronic obstructive pulmonary disease and hypercapnic encephalopathy BMC Pulm Med. 2013; 12;13:12.


Corresponding author:

Killen H. Briones Claudett MSc, MD

Phone: 593987102550 - 59389097152


Address: Panama y Roca


Universidad de Guayaquil. Facultad de Ciencias Médicas. Guayaquil, Ecuador

Friday, June 16, 2017

We appreciate an opportunity to respond to an attempt by Ohira et al.1 to "clarify" an inconsistency between conclusions of the international organizations and our study2 regarding the health impact of radiation exposure from the 2011 Fukushima Daiichi nuclear power plant (FDNPP) accident.

Ohira et al.1 cited four references3-6 in their criticism that our paper2 "suffered from fundamental limitations: unsuitable geographic classifications, disregard of the slow-growing nature of thyroid cancer and its relation with radiation dose, and inappropriate statistical methods."

The geographic classification of Fukushima Prefecture into nine districts was not arbitrary but attained by taking into consideration the schedule sequence of the thyroid screening program launched by the prefecture, wherein the whole prefecture was divided into three areas in the order of screening: the nearest area to the FDNPP in Fiscal Year (FY) 2011; the middle area in FY 2012; and the least contaminated area in FY 2013. The middle and the least contaminated areas were further divided into four districts each, by separating the three most populated cities—Fukushima City, Koriyama City, and Iwaki City—to minimize variance, creating nine districts.

Regarding "the slow-growing nature of thyroid cancer"1, 56 (81%) of 69 thyroid cancer cases detected by cytology in the second round screening did not have any nodules in the first round. These 56 cases had tumors that apparently grew from undetectable to more than 5.0 mm during 2.5 years in-between the two rounds. As for the relation with radiation dose, it is meaningless to solely depend on inference from a known dose-response relation when the dose estimates are widely distributed among various reports2. In addition, lack of individual dose estimates in Fukushima, as appropriately mentioned by Davis6, leads incidence rate ratio towards the null, resulting in underestimation in the sensitivity analysis.

The claim of "inappropriate statistical methods" lacked any specific reference to our statistical methods1. Takahashi et al.4, cited by the authors, only pointed out "mean latent duration" which we assigned 4 years to estimate incidence rate ratio. As we responded1, our conclusion would not change no matter what number of years—anywhere from one to several decades within a realistic human life—was assigned in the sensitivity analysis. Another reference cited, Takamura5, introduced prevalence in unexposed groups in Japan without any statistical inference, including the "distorted" prevalence at Okayama University7. Furthermore, Takamura5 compared Fukushima cancer cases within 5 years after the accident with the Chernobyl cancer cases observed more than 12 years after the accident in those under age 5 at exposure.  

The authors' criticism that our paper "suffered from fundamental limitations" has no fundamental basis.

Next, our critiques concern two issues.

First, it is not true that their classification of highest dose area was "exactly the same" as the "Group 1" defined in the WHO report8. The WHO's preliminary dose estimation9, based on the 2013 report, excluded areas within 20 km from the FDNPP. The authors, however, included residents in the 20 km zone mostly as "Group 2" shown in Figure 1. Moreover, estimated doses for 10-year-old children and 1-year-old infants were the same in "Group 2" and "Group 3" in the WHO's 2012 report9 (Table 2 in pages 44-45; Table 4 in pages 46-47).

Second, they conducted only internal comparison within Fukushima Prefecture, when every data and reports indicate almost the entire prefecture, even "Group 3," was exposed as mentioned in our paper2. What is of critical interest here is not the variability of thyroid cancer within the prefecture but thyroid cancer as a potential health effect of the nuclear accident. This can be estimated by comparison with data outside the prefecture, or pre-accident data in the prefecture which is nonexistent. Thus our comparison was made with the Japanese national data before the accident as well as the Chernobyl data of the unexposed and the relatively low exposed, showing more than 20-fold excess of thyroid cancer2.

Corresponding author

Toshihide Tsuda, MD, PhD (Graduate School of Environmental and Life Science, Okayama University)

3-1-1, Tsushima-naka, Okayama, 700-8530, JAPAN



1. Ohira T, Takahashi H, Yasumura S, Ohtsuru A, Midorikawa S, Suzuki S, Fukushima T, Shimura H, Ishikawa T, Sakai A, Yamashita S, MD, Tanigawa K, Ohto H, Abe M, Suzuki S, and for the Fukushima Health Management Survey Group: Comparison of childhood thyroid cancer prevalence among 3 areas based on external radiation dose after the Fukushima Daiichi nuclear power plant accident. The Fukushima health management survey. Medicine 2016; 95:35(e4472)

2.Tsuda T (Tsuda 2016a), Tokinobu A, Suzuki E, Yamamoto E: Thyroid Cancer Detection by Ultrasound among Residents Aged 18 Years and Younger in Fukushima, Japan: 2011 to 2014. Epidemiology 2016; 28; 316-322.

3.Williams D. Thyroid growth and cancer. Eur Thyroid J 2015;4:164–73.

4.Takahashi H, Ohira T, Yasumura S, et al. Re: thyroid cancer among young people in Fukushima. Epidemiology 2016;27:e21.

5.Takamura N. Re: thyroid cancer among young people in Fukushima. Epidemiology 2016;27:e18.

6.Davis S. Screening for thyroid cancer after the Fukushima disaster. What do we learn from such an effort? Epidemiology 2016;27: 323–5.

7.Tsuda T (Tsuda 2016b), Tokinobu A, Suzuki E, Yamamoto E: The Authors Respond. Epidemiology 2016; 28; e21-e23.

8.World Health Organization. 1. Introduction, 2. Methodology, and 3. Results. Preliminary Dose Estimation from the Nuclear Accident after the 2011 Great East Japan Earthquake and Tsunami. Geneva: WHO Press; 2012:13–47.

9.World Health Organization. 5. Risk characterization. Health Risk Assessment from the Nuclear Accident after the 2011 Great East Japan Earthquake and Tsunami Based on a Preliminary Dose Estimation. Geneva: WHO Press, 2013;51–69.