On 2018 Feb 04, Sin Hang Lee commented:

The medical profession, including medical schools and hospitals, is now a part of the health care industry, and implementation of editorial policies of medical journals is commonly biased in favor of business interests. PubMed Commons has offered the only, albeit constrained, open forum to air dissenting research and opinions in science-based language. Discontinuation of PubMed Commons will silence any questioning of the industry-sponsored promotional publications indexed in PubMed.

On 2017 Aug 20, Sin Hang Lee commented:

Since the lead author and several co-authors of this report are officers of the Centers of Disease Control and Prevention (CDC), the CDC should clarify if this metabolomics-driven technology is now officially recommended for clinical laboratory tests for the diagnosis of emerging infectious diseases in general, or it is created in competition against the well-established 16S rRNA sequence analysis in bacterial infections [1,2] which should be used for molecular diagnosis of Lyme borreliosis. To rely on finding metabolic biosignature consisting of molecular features in patient body fluids to diagnose or to distinguish between emerging infectious diseases is an unproven technology and may have untoward consequences. Would these authors propose using metabolic biosignature in the blood of patients to diagnose Ebola or to distinguish between Ebola and malaria? Of course not!

The authors cited two articles published by other investigators [3,4] to support their novel approach. However, in one of these articles [3] metabolomics were reported to be used as a tool in precision medicine for disease risk assessment and customized drug therapy in clinics. In the other [4], metabolomics were used as a tool to identify the chemical differences that contribute to health and disease, such as chronic fatigue syndrome. Neither concerned diagnosis of or distinguishing between infectious diseases.

The authors claimed to have “previously demonstrated that metabolic profiling of sera provided a high level of accuracy in differentiating early Lyme disease patients from healthy individuals …” [5]. However, in the latter cited article the same lead author [5] stated that it was only a study of “proof-of-concept for a novel diagnostic approach” and that “the early LD biosignature correctly diagnosed 77%–95% of 2-tier negative early LD patients”. That means there was an up to 23% failure in detecting early Lyme disease. Even this statistical model is highly questionable since the very case definition of early Lyme disease is still open to question. According to the CDC's answer to the question: “Is PCR useful for the diagnosis of Lyme disease? In general, the answer is no.” [6].

The claim to have discovered an objective, diagnostically useful “metabolic biosignature” of Lyme disease or STARI which are both emerging infectious diseases, by analysis of a set of metabolites in tissue fluids of the patients must be supported by undisputed evidence with proven scientific principles. The authors’ novel approach in fact has deviated from the classic teachings of diagnostic microbiology. The findings of metabolic differences between patients with Lyme disease and patients with STARI do not automatically yield a test that can be used to diagnose or to distinguish between Lyme disease and STARI.

Conflicts of Interest: Sin Hang Lee, MD is the director of Milford Molecular Diagnostics Laboratory specialized in developing DNA sequencing-based diagnostic tests. References: [1] https://www.cdc.gov/labtraining/docs/588-100_103-17_16S_rRNA_Sequence_Based_Bacterial_Identification.pdf [2] https://www.cdc.gov/microbenet/about.html [3] Guo L, Milburn MV, Ryals JA, et al. Plasma metabolomic profiles enhance precision medicine for volunteers of normal health. Proc Natl Acad Sci U S A. 2015 Sep 1;112(35):E4901-10. [4] Naviaux RK, Naviaux JC, Li K, et al. Metabolic features of chronic fatigue syndrome. Proc Natl Acad Sci U S A. 2016 Sep 13;113(37):E5472-80. [5] Molins CR, Ashton LV, Wormser GP, et al. Development of a metabolic biosignature for detection of early Lyme disease. Clin Infect Dis. 2015 Jun 15;60(12):1767-75. [6] Christina A. Nelson, MD, MPH, Medical Officer in the Bacterial Diseases Branch of CDC's Division of Vector-Borne Disease. http://www.medscape.com/viewarticle/764501?src=par_cdc_stm_mscpedt&faf=1 Last accessed August 19, 2017.

On 2017 Aug 20, Sin Hang Lee commented:

Since the lead author and several co-authors of this report are officers of the Centers of Disease Control and Prevention (CDC), the CDC should clarify if this metabolomics-driven technology is now officially recommended for clinical laboratory tests for the diagnosis of emerging infectious diseases in general, or it is created in competition against the well-established 16S rRNA sequence analysis in bacterial infections [1,2] which should be used for molecular diagnosis of Lyme borreliosis. To rely on finding metabolic biosignature consisting of molecular features in patient body fluids to diagnose or to distinguish between emerging infectious diseases is an unproven technology and may have untoward consequences. Would these authors propose using metabolic biosignature in the blood of patients to diagnose Ebola or to distinguish between Ebola and malaria? Of course not!

The authors cited two articles published by other investigators [3,4] to support their novel approach. However, in one of these articles [3] metabolomics were reported to be used as a tool in precision medicine for disease risk assessment and customized drug therapy in clinics. In the other [4], metabolomics were used as a tool to identify the chemical differences that contribute to health and disease, such as chronic fatigue syndrome. Neither concerned diagnosis of or distinguishing between infectious diseases.

The authors claimed to have “previously demonstrated that metabolic profiling of sera provided a high level of accuracy in differentiating early Lyme disease patients from healthy individuals …” [5]. However, in the latter cited article the same lead author [5] stated that it was only a study of “proof-of-concept for a novel diagnostic approach” and that “the early LD biosignature correctly diagnosed 77%–95% of 2-tier negative early LD patients”. That means there was an up to 23% failure in detecting early Lyme disease. Even this statistical model is highly questionable since the very case definition of early Lyme disease is still open to question. According to the CDC's answer to the question: “Is PCR useful for the diagnosis of Lyme disease? In general, the answer is no.” [6].

The claim to have discovered an objective, diagnostically useful “metabolic biosignature” of Lyme disease or STARI which are both emerging infectious diseases, by analysis of a set of metabolites in tissue fluids of the patients must be supported by undisputed evidence with proven scientific principles. The authors’ novel approach in fact has deviated from the classic teachings of diagnostic microbiology. The findings of metabolic differences between patients with Lyme disease and patients with STARI do not automatically yield a test that can be used to diagnose or to distinguish between Lyme disease and STARI.

Conflicts of Interest: Sin Hang Lee, MD is the director of Milford Molecular Diagnostics Laboratory specialized in developing DNA sequencing-based diagnostic tests. References: [1] https://www.cdc.gov/labtraining/docs/588-100_103-17_16S_rRNA_Sequence_Based_Bacterial_Identification.pdf [2] https://www.cdc.gov/microbenet/about.html [3] Guo L, Milburn MV, Ryals JA, et al. Plasma metabolomic profiles enhance precision medicine for volunteers of normal health. Proc Natl Acad Sci U S A. 2015 Sep 1;112(35):E4901-10. [4] Naviaux RK, Naviaux JC, Li K, et al. Metabolic features of chronic fatigue syndrome. Proc Natl Acad Sci U S A. 2016 Sep 13;113(37):E5472-80. [5] Molins CR, Ashton LV, Wormser GP, et al. Development of a metabolic biosignature for detection of early Lyme disease. Clin Infect Dis. 2015 Jun 15;60(12):1767-75. [6] Christina A. Nelson, MD, MPH, Medical Officer in the Bacterial Diseases Branch of CDC's Division of Vector-Borne Disease. http://www.medscape.com/viewarticle/764501?src=par_cdc_stm_mscpedt&faf=1 Last accessed August 19, 2017.

On 2018 Feb 04, Sin Hang Lee commented:

The medical profession, including medical schools and hospitals, is now a part of the health care industry, and implementation of editorial policies of medical journals is commonly biased in favor of business interests. PubMed Commons has offered the only, albeit constrained, open forum to air dissenting research and opinions in science-based language. Discontinuation of PubMed Commons will silence any questioning of the industry-sponsored promotional publications indexed in PubMed.