Hydroxychloroquine

Autophagy occurs in tumor cells acquiring cytotoxic drug resistance and its activation may impair their susceptibility to apoptosis in response to apoptogen agents. We investigated the pro-apoptotic effect of dexamethasone (Dex) on MM cell lines (U266, INA-6, LR5-8226, LIG, and MCC2) and primary malignant plasma cells from naïve and refractory/relapsed patients. We evaluated the transcriptional and ultrastructural events leading to autophagy by measuring Beclin-1 and p62 levels and transmission electronic microscopy. Autophagy was inhibited by hydroxychloroquine (HCQ), whereas the ability of Dex-resistant MM cells to recover the susceptibility to apoptosis was measured. A direct relationship between autophagy and Beclin-1 or LC3/Atg8 levels was observed, whereas their mRNAs were inversely correlated to p62 expression. Starvation strongly activated autophagy by inducing cellular, transcriptional, and ultrastructural modifications that were reversed by HCQ. Taken together, these data ...

Plaquenil (hydroxychloroquine. HCQ; Sanofi W inthrop Pharmaceuticals. New York. NY) is a stereoisomeric drug administered as a racemic (50 : 50) mixture of two isomeric forms-(+) and (-) HCQ. To correlate clinical efficiency accurately with dose. it is necessary to determine the fate of both isomers. This will allow for the optimization of clinical dosing. A method has been developed for the quantitation of (+) and ( -) HCQ and its rnajor metabolites , desethylhydroxychloroquine (DHCQ), desethylchloroquine (DCQ), and bisdesethylchloroquine (BDCQ). in plasma and in urine.

Hydroxychloroquine (HCQ) is a halogenated aminoquinoline that presents wide biological activity, often being used as an antimalarial drug. The electrochemical reduction of HCQ was investigated by cyclic voltammetry and chronoamperometry using glassy carbon electrodes. By cyclic voltammetry, in acid medium, only the cathodic peak was observed. The electrochemical behavior of this peak is dependent on pH and the electrodic process occurs through an E r C i mechanism. The electron number (1e) consumed in the reduction of HCQ was obtained by chronoamperometry. A method for the electrochemical determination of HCQ in pharmaceutical tablets was developed using differential pulse voltammetry. The detection limit reached was 11.2 mg ml (1 of HCQ with a relative standard deviation of 0.46%. A spectrophotometric study of HCQ has been also carried out utilizing a band at 343 nm. The obtained detection limit and the relative standard deviation were 0.1 mg ml (1 and 0.36%, respectively. The electrochemical methods are sufficiently accurate and precise to be applied for HCQ determination, in laboratorial routine, which can be used to determine the drug at low level.

Basic all-cause US death data for 2020, when reviewed in light of a claimed Covid-19 pandemic, suggest most annual excess deaths are due to the physical consequences of lockdown-related mandates which create economic ruin and added emotional and somatic-pathological devastation within vulnerable populations. The CDC's data on Covid-19 lab-confirmed tests, cases and deaths were reviewed as plotted on the same ordinate vertical axis scale, indicating a high correlation between tests and cases, but no correlations or causality between either tests or cases to deaths. Covid-19 deaths among age-groups of high-risk elderly 65+ years and older, were found to be of nearly identical percentages as in all-cause deaths in the same age demographic. Daily death/case ratios failed to affirm any significant global growth or spread of an expected deadly viral pandemic. Claimed Covid-19 deaths followed a dominant seasonal wintertime pattern, peaking within the different winter months of the two hemispheres. These direct reviews of the official data exposed multiple contradictions to basic causality and logic, revealing observed pathology and deaths are primarily due to extreme lockdown measures undertaken to control a presumed viral pandemic, but not to any viral pandemic itself. Problems in PCR/Antigen tests and electron-microscopy for specific identification of SARS-CoV-2 were exposed, indicating the claimed Covid-19 lab tests and clinical diagnoses are, at high numbers, inaccurately mis-attributing ordinary end-of-life diseases and conditions to a poorly-demonstrated virus. This is why lab-confirmed cases among asymptomatic people who remain healthy have soared to dramatically high numbers, while lab-confirmed deaths have not. All-cause death data suggest respiratory disorders such as influenza or pneumonia are being inappropriately reclassified as Covid-19. Soaring "case" numbers reflect herd immunity only, while increased death numbers are due to comorbidities made worse in vulnerable populations by forced lockdowns and economic ruin.

Hydroxychloroquine (HCQ) has been shown to disrupt autophagy and sensitize cancer cells to radiation and chemotherapeutic agents. However, the optimal delivery method, dose, and tumor concentrations required for these effects are not known. This is in part due to a lack of sensitive and reproducible analytical methods for HCQ quantitation in small animals. As such, we developed and validated a selective and sensitive liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method for simultaneous quantitation of hydroxychloroquine and its metabolites in mouse blood and tissues. The chromatographic separation and detection of analytes were achieved on a reversed phase Thermo Aquasil C18 (50×4.6mm, 3μ) column, with gradient elution using 0.2% formic acid and 0.1% formic acid in methanol as mobile phase at a flow rate of 0.5mL/min. Simple protein precipitation was utilized for extraction of analytes from the desired matrix. Analytes were separated and quantitated using MS...

The nature of overall health construed using a World War II analogy with Covid-19, bio-agent factors(Anthrax, Plague, Botulism), chemical elements, and tunnel warfare embedded into that framework.

"The technology used by NASA to foresee sinkholes in
advance could correlate into technology used to locate tunnels from
observing radar systems."

This is extracted from the physical copy of "Ares Le Mandat" that has the beige cover on Amazon

Background: 2019-nCoV/SARS-CoV-2 or most commonly novel coronavirus has become extremely important
considering the pandemic situation declared by WHO on 11th March 2020. It has become a prime aim to the
researchers to understand it’s pathological, clinical, structural and transmission parameters. Though the report
was first registered from Wuhan, China but gradually it has spread worldwide. In the present work the role of
meteorological variables dependent immune system with the severity of the outbreak was surveyed on a world
wide scale. This meteorological correlation model will provide some important information to any government
for their future plan of action to get control over the rapid spread of SARS-CoV-2. The confirmed case counts of
COVID-19 and meteorological variables were collected systematically from World Health Organization and
website and World Meteorological Organization website on 29th March 2020. A systematic growth of the
infection rate and population density of that particular country was also considered in this research.
Materials and Methods: In the present work the countries affected severely by COVID-19 is divided into two
parts, one group situated between the latitude of 150
to 300
and other between 450
to 600
in both the
hemisphere. Continuous monitoring was done through WHO official website to collect the raw data of COVID-
19 infected people from the countries particularly suffering from 3rd stage of community transmission and the
maximum and minimum temperature of those countries during the last fifteen days of March is recorded from
World Meteorological Organization. From the raw data heavily populated countries were taken into
consideration for analysis.
Results: It is clearly observed that at the equatorial zone that is between latitude ranges 150
to 450
, the rate of
transmission is low whereas between the latitude ranges 450
to 600
the transmission of viral infection is very
high. Rate of transmission is naturally lesser in few countries due to its low population density. According to the
guide line of WHO and the official pathological reports published in different country , it is observed that
COVID-19 is not airborne but it transmit either in direct or indirect contact. Hence density of population and
number of migrating people plays very vital role. But apart from these parameters, temperature plays an
important role in the immune system of human body and on the pathogenic character of such RNA virus.
Conclusion: The collected data from 57 countries and more than 600000 people around the world and its
corresponding graph gives a very clear trend about the 2019-nCoV/SARS-CoV-2 or most commonly novel
coronavirus infection transmission rate. The analysis represents that there will be gradual decrease of infection
transmission rate with the natural hike of temperature. In this case may be Stromal interaction molecule
1(STIM1) is activated moderately with high degree of temperature. Most commonly used drug Chloroquine, due
to Malaria, interferes with ACE2 receptor glycosylation, which prevents SARS-CoV-2 to bind with the target
cells may also be very important factor to reduce the transmission of infection.
Key Word: SARS-CoV-2, COVID-19, temperature, immune system, population density
---------------------------------------------------------------------------------------------------------------------------------------
Date of Submission: 29-03-2020 Date of Acceptance: 09-04-2020

BULLET-POINT SUMMARY:

• Antivirals did not play a significant role in helping curb previous coronavirus outbreaks — SARS and MERS largely went away on their own, through public health measures that helped contain the spread.
• Present coronavirus trials using antivirals have to this point on the whole proved either inconclusive or disappointing.
• Azithromycin, an antibiotic with no antiviral activity whatsoever, is proving quite efficacious in treating the disease behind the “COVID-19” pandemic. Azithromycin is a first-line drug against Mycobacterium avium, which can simulate obstructive lung disease, and every other sign or symptom of COVID-19 documented to date.  In addition azithromycin is a second or third-line drug against drug-resistant Mycobacterium tuberculosis.
• There was and still is a Pandemic going on in the world which dwarfs coronavirus. A Pandemic which kills one person every 21 seconds. A pandemic which in 2018 alone killed at least 1.5 million people annually. A mycobacterial pandemic, from Mycobacterium tuberculosis.
• In the United States, pulmonary Mycobacterium avium complex (MAC) disease or “fowl tuberculosis” is more common than tuberculosis
• Furthermore, Mycobacterium avium complex is now the leading mycobacterial cause of chronic pneumonia in the United States.
• Infections due to non-tuberculous mycobacteria (NTM) such as Mycobacteria avium are increasing worldwide, and are particularly important to take into account when considering a zoonosis, which COVID-19 was originally thought to be.
• Not only does the drug hydroxychloroquine inhibit intracellular TB, but it acts synergistically against mycobacterial disease when combined with certain antimycobacterials. Azithromycin is also used as an antimycobacterial.
• The BCG tuberculosis vaccine is currently the focus of an international 4 country study to combat the Coronavirus pandemic.
• In the present Coronavirus pandemic, tubercular infection is by far the most common co-morbidity or underlying condition.
• A Recent preliminary Chinese study shows that tubercular infection likely increases susceptibility to SARS-CoV-2, and also increases COVID-19 severity.

In a disaster, the coronavirus pandemic providing a ready example, cries to abandon caution and gamble on solutions can lead to spectacular success and deadly failures.

President Trump continues to tout an antibiotic and anti-viral drug called hydroxychloroquine as a potential treatment for Covid-19. More than just promoting the treatment, Trump urges its use, including prophylactic use.

With regard to efficacy, Trump said, "It may work, it may not." Moreover, because the drug has proven relatively safe when used under other specific circumstances (e.g., treatment of malaria, lupus, rheumatoid arthritis, and other autoimmune diseases), Trump asserts, "What is there to lose?"

At a minimum, a loss of scientific rigor and the potential to repeat some of the same mistakes made the hasty FDA approval of azidothymidine, aka AZT or Retrovir, in 1987. Like hydroxychloroquine, AZT wasn't a new compound, it was created in the 60s as chemotherapy drug. AZT proved ineffective for that purpose but was dusted off and, in desperation to stem rising HIV/AIDS deaths, tried as an anti-viral. Encouraging success from flawed trials and political pressure pushed the FDA into a rapid approval. While AZT arguably offered some benefits, and became part of the cocktail of drugs developed in the 90s to control AIDS, patients also suffered debilitating side effects, problems related to over dosage, and drug resistance.

In the current battle against SARS-CoV-2 and Covid-19 pandemic, the FDA has granted an emergency use authorization for hydroxychloroquine, and clinical use of the drug has been tried in China, Italy, and other places where critically ill patients had no other options. There is a spectrum of anecdotal evidence, from highly encouraging to "of no use" to potentially dangerous.

I hope the president is right, but even if he is ultimately proven correct then it's not because of his scientific insight but rather prophetic fulfillment of the saying, "Even a blind squirrel occasionally finds a nut." He certainly isn't using science.

In support of using hydroxychloroquine, Trump cites a "French study" that he claims shows "spectacular" or "encouraging" results. Alas, the paper announcing the French group's findings, 'Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial' (published in the International Journal of Antimicrobial Agents (IJAA) (See Note #1) was subsequently denounced by the journal's publisher, the International Society of Antimicrobial Chemotherapy (ISAC), who said that the organization "shares the concerns regarding the above article published recently in the International Journal of Antimicrobial Agents (IJAA). The ISAC Board believes the article does not meet the Society’s expected standard, especially relating to the lack of better explanations of the inclusion criteria and the triage of patients to ensure patient safety." (See Note #2)

Originally published 22 March, 2020.

(download to read more)

In the current work, we discovered and analyzed the epidemiological paradox between coronavirus disease 2019 (COVID-19) and malaria in the initial phase of the ongoing pandemic. From the analysis of distribution data, the endemic presence of malaria seems to protect some populations from COVID-19 outbreak, particularly in the least developed countries. In this sense, molecular and genetic variations associated with malaria (e.g., in ACE2) might play a protective role against coronavirus infection. Moreover, the mechanism of action of some antimalarial drugs, e.g., the antiviral function, suggests their potential role in the chemoprophylaxis of coronavirus epidemics, despite possible adverse effects (e.g., retinal toxicity). All these data provide important insights to understand the spreading mechanisms of COVID-19, and to direct scientific research toward the study of some currently available medications.

La crise sanitaire provoquee par la pandemie de la Covid-19 a engendre de nombreuses incertitudes quant au mode de propagation du coronavirus SARS-CoV-2, de l’identification des symptomes de la maladie, de la duree probable de la pandemie et surtout des traitements a administrer. De nombreux professionnels de sante furent alors sollicites par les medias pour delivrer leur expertise medicale sur cette nouvelle maladie, ses traitements, sa propagation, les moyens de l’enrayer, les gestes a suivre et a ne pas suivre. La population francaise a alors acquis, a vitesse acceleree, des connaissances medicales complexes (comme le test PCR) au gre des enseignements dispenses dans les medias par les infectiologues, virologues, epidemiologistes, microbiologistes, urgentistes, reanimateurs, pharmaciens ou generalistes interroges. Dans ce contexte particulierement anxiogene, les medias (presse ecrite, radio, et television) ont relaye de vifs debats entre les partisans du traitement de la Covid-19...

See above the second part:
Facts or Values, that is the Question (The Lancet-NEJM Hydroxychloroquine Scandal-2)

It was claimed that a combination of hydroxychloroquine and azithromycin may have some preventive effects for Covid-19 infection. Nevertheless, this has been challenged between others by two large retrospective clinical studies, by a group from Harvard Medical School, whose articles were published in The Lancet and the New England Journal of Medicine and then 10 days after, the articles were retracted because of legal reasons. We claim no knowledge about the efficacy of the hydroxychloroquine (HCQ) and do not discuss the agent at all. However, here we claim that besides legal reasons, the methodological reasons for the withdrawal of the papers were even more important. The patients that receive HCQ during spring 2020. were predominantly the high-risk patients and it was not possible to have a retrospective study that would not suffer from selection bias. This means that the studies compared incomparable groups and failed to demonstrate the link between the agent and the outcome. The error is so flagrant that it is impossible that the investigators, 3 highest medical authorities as well as and primarily The Lancet or NEJM reviewers, overlooked it. We proposed that even if correctly performed, some eventual Randomised Controlled Trial ( RCT) will be very hard to interpret because of always present potential various hidden errors and that the conclusion of such studies should always be taken with much reserve. Probably some more reliable methods of clinical research should be developed in the future.

Keywords: hydroxychloroquine, chloroquine, Covid-19, Randomised Controlled Trials, The Lancet, retracted article.


https://www.mediterranee-infection.com/the-lancet-covid-19-therapy-study-another-miss-out/

https://www.mediterranee-infection.com/wp-content/uploads/2020/06/Covid-Lancet-5-1-BOOK.pdf

Lichen planopilaris (LPP) and its variant frontal fibrosing alopecia (FFA) are primary lymphocytic cicatricial alopecias for which there is no evidence-based therapy.We assessed the efficacy of hydroxychloroquine in active LPP and FFA using the LPP Activity Index (LPPAI), a numeric score that allows quantification of the symptoms and signs of the condition for statistical comparison. In addition, we determined with the LPPAI if any improvement (reduction) in the numeric score pretreatment and posttreatment reached statistical significance.This was a retrospective, single-center chart review of 40 adult patients with LPP, FFA, or both who were treated with hydroxychloroquine for up to 12 months from 2004 to 2007 at the University of California, San Francisco Hair Center. Symptoms, signs, activity, and spreading were scored at each visit in the standardized cicatricial alopecia flow chart. A numeric score was assigned to these markers of disease activity and a numeric score was calculated at each visit.There was significant reduction (P < .001) in the LPPAI at both 6 and 12 months. After 6 months, 69% had improved (reduced) symptoms and signs. At 12 months, 83% had improvement (reduction) in symptoms and signs.Retrospective analysis and uncontrolled study are limitations.Hydroxychloroquine is effective in decreasing symptoms and signs in LPP and FFA as shown by significant reduction in the LPPAI in 69% and 83% of patients after 6 and 12 months of treatment, respectively.

Influence of environmental temperature on the occurrence of non-necrotizing cellulitis of the leg SIR, Non-necrotizing cellulitis of the leg is a common cutaneous bacterial infection whose risk factors include venous insufficiency, lymphoedema and toe-web intertrigo. The role of environmental temperature remains controversial. 1 To study the relationship between environmental temperature and the frequency of non-necrotizing cellulitis of the leg, we reviewed all patients hospitalized with nonnecrotizing cellulitis of the leg in a university hospital in a temperate region of France during a 4-year period, and correlated findings with the local environmental temperature during the same period.

The pharmacophoric space of glycogen synthase kinase-3 (GSK-3 ) was explored using two diverse sets of inhibitors. Subsequently, genetic algorithm and multiple linear regression analysis were employed to select optimal combination of pharmacophores and physicochemical descriptors that access self-consistent and predictive quantitative structure-activity relationship (QSAR) against 132 training compounds (r 2 123 ) 0.663, F ) 24.6, r 2 LOO ) 0.592, r 2 PRESS against 29 external test inhibitors ) 0.695). Two orthogonal pharmacophores emerged in the QSAR, suggesting the existence of at least two distinct binding modes accessible to ligands within GSK-3 binding pocket. The validity of the QSAR equation and the associated pharmacophores was established by the identification of three nanomolar GSK-3 inhibitors retrieved from our in-house-built structural database of established drugs, namely, hydroxychloroquine, cimetidine, and gemifloxacin. Docking studies supported the binding modes suggested by the pharmacophore/QSAR analysis. In addition to being excellent leads for subsequent optimization, the anti-GSK-3 activities of these drugs should have significant clinical implications. a Abbreviations: GSK-3, glycogen synthase kinase-3; QSAR, quantitative structure-activity relationship; MLR, multiple linear regression; GFA:, genetic function algorithm; HBA, hydrogen bond acceptor; HBD, hydrogen bond donor.

Background: Osteoarthritis (OA) is the most common type of arthritis, causing significant joint pain and disability. It is already a major cause of healthcare expenditure and its incidence will further increase with the ageing population. Current treatments for OA have major limitations and new analgesic treatments are needed. Synovitis is prevalent in OA and is associated with pain. Hydroxychloroquine is used in routine practice for treating synovitis in inflammatory arthritides, such as rheumatoid arthritis. We propose that treating patients with symptomatic hand OA with hydroxychloroquine will be a practical and safe treatment to reduce synovitis and pain.

We have investigated the effect of hydroxychloroquine (HCQ), an anti-rheumatic drug, on malignant B cells from 20 patients with B-chronic lymphocytic leukaemia (B-CLL). HCQ induced a decrease in cell viability in a dose-and time-dependent manner. The mean IC50 was 32^7 mg/ml (range, 10-75 mg/ml) for 24 h of exposure. This cytotoxic effect was owing to apoptosis, as demonstrated by morphological changes, annexin V binding capacity and DNA fragmentation (28^4% of apoptotic cells as early as 5 h post incubation, increasing to 82^4% at 18 h post treatment). The apoptosis was associated with caspase-3 activation because the cleavage and activity of caspase-3 were increased by HCQ. The amount of bcl-2 protein was reduced during apoptosis, evidenced using quantitative flow cytometry. As early as 1 h post-HCQ treatment, a reduction of the mitochondrial transmembrane potential was measured by 3,3'-dihexyloxacarbocyanine iodide. Interestingly, the HCQ effect was not affected by exposure to interleukin-4 or co-culture with bone marrow stromal cells. Our observations suggest that HCQ may offer a new therapeutic tool in the treatment of B-CLL patients.

Multifocal ERG ring ratios provide a sensitive and objective method to detect ocular toxicity in patients taking hydroxychloroquine (Plaquenil). In order to measure ring ratios, the average mfERG amplitude was calculated for each of five concentric rings of a 61-hexagon mfERG. The age-corrected amplitude of the central hexagon (R 1 ) and the ratios of R 1 to each of the successive rings (R 1 /R 2 , R 1 /R 3 , etc.) were then computed. Normative values for ring ratios were established from a population of 67 normal controls. In the study population, a ring was considered abnormal if it was above the 99% confidence limits for the normal population. The technique was evaluated on 131 eyes of 62 patients taking Plaquenil for a variety of conditions including rheumatoid arthritis, systemic lupus erythematosus, and Sjögren's syndrome. Patients who had taken Plaquenil for an extended period showed a higher incidence of retinal toxicity, regardless of the condition for which they were taking the drug. Among patients who had taken a cumulative dose of less than 1,250 g, 7 of 67 eyes (10%) showed a characteristic mfERG defect, while in patients with a cumulative dosage of 1,250 g or more, 26 of 64 eyes (41%) showed one of these defects. In at least one patient, the technique was able to detect the early onset of Plaquenil toxicity followed by reversal of the toxic effects after the medication was discontinued. It appears appropriate to recommend that mfERG testing be done on all patients on Plaquenil therapy.

The severe acute respiratory syndrome caused by the new coronavirus SARS-Cov-2 (COVID-19) has quickly turned into a pandemic, infecting more than 10 million people and causing more than 500,000 deaths worldwide. The absence of an effective treatment against this disease has led several researchers to investigate the possibility of redirecting drugs already known to be effective against other diseases in the treatment of COVID-19, among them the antimalarial drugs chloroquine and hydroxychloroquine. This review aims at showing how chloroquine and hydroxychloroquine came to be considered as possible drugs in the treatment of COVID-19 and how the recent in vivo experiments described so far shed light on the adequacy of this use.

The antimalarials are one of the most commonly prescribed drugs in medical practice, for conditions such as rheumatoid arthritis as well as malaria. They are generally well-tolerated and the possible side effects of synthetic antimalarials, though infrequent, are well known. Besides the familiar adverse reactions, a localized mucocutaneous bluish-grey to black discolouration can sometimes be seen with antimalarial drugs. The aim of this report was to draw attention to the localized mucocutaneous bluish-grey hyperpigmentation induced by hydroxychloroquine with a case presentation and a review of the literature.

The focus of this study is identification and characterization of major unknown impurities in chloroquine (CQ) and hydroxychloroquine (HCQ) bulk drug samples using liquid chromatography/ion trap mass spectrometry (LC/IT/MS) and liquid chromatography/time of flight mass spectrometry (LC/TOF/MS). The newly developed LC/MS method was employed for the analysis of both the drugs. The analysis revealed the presence of two impurities in each of the drugs. The impurities are designated as CQ-I, CQ-II (for chloroquine); HCQ-I and HCQ-II (for hydroxychloroquine). Three of the impurities, CQ-II, HCQ-I and HCQ-II were unknown have not been reported previously. Accurate masses of the impurities were determined by using Q-TOF mass spectrometer and fragmentation behavior was studied by an ion trap mass spectrometer. Based on the spectrometric data and synthetic specifics the structures of CQ-II, HCQ-I and HCQ-II were proposed as 1,4 pentanediamine, N 4 (7-chloro-4-quinolinyl), N 4 -chloromethyl, N 4 -ethylamine; 2-(4-(7-chloroquinolin-4-ylamino) pentylamino) ethanol and [[4-[(7-chloro-4-quinolyl) amino] N-pentyl] N-chloromethyl-N-ethylamino] ethanol respectively. The impurities were isolated by semi-preparative HPLC and structures were confirmed by NMR spectroscopy. The formation and through characterization of known CQ-I impurity is also discussed.

is an uncommon complication of the use of D-penicillamine and sulphasalazine. We report two cases of patients with rheumatoid arthritis (RA) who developed symptoms and signs of SLE and suggest that increasing use of these two agents as combination therapy in RA may cause an additive risk to the occurrence of this complication.

A rare case of childhood pulmonary haemosiderosis with juvenile idiopathic arthritis is discussed, with particular reference to treatment with hydroxychloroquine and sildenafil for pulmonary hypertension which occurs secondary to this disease.

IMPORTANCE Given the infrequent occurrence of hydroxychloroquine toxic effects, few data are available about the presenting features and long-term follow-up of patients with hydroxychloroquine retinopathy, making it difficult to surmise the clinical course of patients after cessation of drug treatment. OBJECTIVE To report functional and structural findings of hydroxychloroquine retinal toxic effects after drug therapy discontinuation. DESIGN A retrospective medical record review was performed to identify patients taking hydroxychloroquine who were screened for toxic effects from PARTICIPANTS Seven consecutive patients diagnosed as having hydroxychloroquine retinal toxic effects.

Skin involvement in dermatomyositis does not always parallel muscle disease and can be the most active or severe component of the disease, failing to respond to therapeutic interventions that are adequate for myositis and other systemic involvement. This case refers to a resistant paraneoplastic amyopathic dermatomyositis rash which readily resolved with intravenous immunoglobulin (IVIG), practically in the form of monotherapy. This observation gains particular significance considering that IVIG is still regarded as a second-line therapeutic regimen in the treatment of dermatomyositis despite its prevalence in matters of safety.

The focus of this study is identification and characterization of major unknown impurities in chloroquine (CQ) and hydroxychloroquine (HCQ) bulk drug samples using liquid chromatography/ion trap mass spectrometry (LC/IT/MS) and liquid chromatography/time of flight mass spectrometry (LC/TOF/MS). The newly developed LC/MS method was employed for the analysis of both the drugs. The analysis revealed the presence of two impurities in each of the drugs. The impurities are designated as CQ-I, CQ-II (for chloroquine); HCQ-I and HCQ-II (for hydroxychloroquine). Three of the impurities, CQ-II, HCQ-I and HCQ-II were unknown have not been reported previously. Accurate masses of the impurities were determined by using Q-TOF mass spectrometer and fragmentation behavior was studied by an ion trap mass spectrometer. Based on the spectrometric data and synthetic specifics the structures of CQ-II, HCQ-I and HCQ-II were proposed as 1,4 pentanediamine, N 4 (7-chloro-4-quinolinyl), N 4 -chloromethyl, N 4 -ethylamine; 2-(4-(7-chloroquinolin-4-ylamino) pentylamino) ethanol and [[4-[(7-chloro-4-quinolyl) amino] N-pentyl] N-chloromethyl-N-ethylamino] ethanol respectively. The impurities were isolated by semi-preparative HPLC and structures were confirmed by NMR spectroscopy. The formation and through characterization of known CQ-I impurity is also discussed.

Antimalarials (AMs) have been demonstrated to reduce disease activity and prevent damage accrual in SLE. Recent guidelines advise prescribing AMs in all patients with SLE. We present data from the Amsterdam Lupus Cohort on use, reasons for non-use, and dosage related intolerance of AMs, as well as disease related variables associated with non-use. AM use was assessed in all our SLE patients included in a longitudinal cohort study. Demographic and disease characteristics were compared between users and non-users of AMs. Daily dosages of hydroxychloroquine (HCQ) according to lean body weight were calculated. Out of 190 SLE patients in the cohort, 139 (73.2%) were using AMs during their last visit, predominantly HCQ (136/139, 97.8%), while 92.1% (175/190) had ever used AMs. Daily dosage of HCQ was 400 mg in 115/136 (84.6%) patients. According to lean body weight, 119/136 (87.5%) had daily dosages of HCQ above the recommended 6.5 mg/kg. Patients did not use AMs (n=51) for the following ...

Hydroxychloroquine (HCQ) is an immunosuppressive lysosomotropic amine that has activity against graftversus-host disease (GVHD). In a single-institution phase III trial, 95 recipients of allogeneic peripheral blood stem cell (PBSC) transplantation were randomized to receive, in a double-blind fashion, and in addition to prophylactic cyclosporine A (CSA), HCQ, or placebo starting 21 days pretransplant and continued until day ؉365. HCQ was very well tolerated and not associated with side effects. Overall, the incidence of acute GVHD (aGVHD) was 59% in both arms, and severe aGVHD occurred in 11% (HCQ) and 14% (placebo) (P ‫؍‬ .76). Sixty percent and 78% of patients developed chronic GVHD (cGVHD) in the HCQ and the placebo arms, respectively (P ‫؍‬ .15). With a median follow-up of 18 months, relapse-free and overall survivals (OS) were comparable in both groups. In summary, in this randomized trial, the addition of HCQ to single-agent CSA had no effects on aGVHD or cGVHD or survival.

The use of hydroxychloroquine (HCQ) in pregnancy remains controversial. The recent demonstration that HCQ passes across the placenta, with cord blood concentrations nearly identical to those found in maternal blood, emphasizes the need for careful evaluation of pregnancies in women receiving HCQ. However, only small series of HCQ-treated pregnant women have been reported, and most of these studies had no control group. We now report our experience with 133 pregnancies in women being treated with HCQ, resulting in 117 live births. Results in the HCQ group are compared with those in a control group. Methods. One hundred thirty-three consecutive pregnancies in 90 women treated with 200 mg of HCQ either twice daily (122 pregnancies) or once daily (11 pregnancies) were studied. These pregnancies were compared with 70 consecutive pregnancies in 53 women with similar disorders who did not receive HCQ. Electrocardiography was performed in 47 children of mothers treated with HCQ and in 45 children in the control group. Results. Eighty-eight percent of pregnancies in the HCQ group and 84% of those in the control group

On or around May 22, 2020, a paper entitled "Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis", authored by Mehra et al. was published by Lancet [Lancet (2020) DOI: 10.1016/S0140-6736(2013)31180-6].  Following, several protestations with respect to the authenticity of the data presented in the said paper, Lancet had no choice but to retract the said paper. In view of the fact that the paper by Mehra et al. contain blatant instances of Data Fabrication, Data Falsification and Dishonest Scientific Reporting, it is legitimate to ask why the paper by Mehra et al. was accepted and published by Lancet in the first place. Was there any so-called peer review before the paper by Mehra et al. was accepted by Lancet. Who are the so-called experts who reviewed the paper by Mehra et al. Should Lancet and other outfits like Lancet initiate an investigation of their so-called independent peer review system.  Who is ultimately responsible for this fiasco. Should the Editor in Chief of Lancet take responsibility for the fiasco by voluntarily resigning and letting someone who is still working at the bench with his/her brains and hands take over. (The former minister of the United Kingdom, Michael Bates, Minister of State in the Department for International Development offered his resignation after being late for a question session by 1 minute). If the Editor in Chief does not wish to resign voluntarily, should the Managing Editors (if we know who they are) of Lancet fire the Editor in Chief of Lancet for being incompetent and ignorant at doing his job. Are there other papers at Lancet that contain Data Fabrication, Data Falsification and Dishonest Scientific Reporting.