Wednesday, December 1, 2021

Stem Cell Therapy in type 1 Diabetes

A 64-year-old man in the U.S. is likely the first patient who was cured from type 1 diabetes.  According to NYT, his body now controls its insulin and blood sugar levels following an infusion of insulin-producing cells grown from embryonic stem cells.

The only cure that has ever worked in patients with type 1 diabetes is either a pancreas transplant or a transplant of the the insulin producing islet cells, from a donor's pancreas.  Because of a shortage of organs such an approach is not an answer for the vast majority of patients with the disease.  The cells infused in this patient were procured from unused fertilised eggs from a fertility clinic.  It took over 20 years and a team of 15 people to successfully convert stem cells into islet cells at a cost of about $50 million.

If this successful treatment can be replicated it will be a major advance in the history of transplantation and will provide hope to 1.5 million Americans who live with the disease. 

Monday, November 1, 2021

Pig Kidney Successfully Transplanted in a Human Patient

An article in NYT reported that surgeons successfully transplanted a genetically altered kidney to a patient and found the organ worked normally.  The kidney was attached to a patient who had suffered brain death and was maintained on a ventilator.   The kidney's vessels were connected to the patient's femoral artery and vein and it lay outside the body while it was observed for 54 hours.  During the nearly three day it was observed it functioned normally, making urine and the waste product creatinine 'almost immediately' according to Dr. Robert Montgomery, the director of N.Y.U. Langone Transplant Institute who performed the procedure in September 2021.  This medical advance is the culmination of years of experimental work that started in the 60s and is a milestone in the quest to successful xenotransplantation which may help the lives of millions of patients around the world. 

Friday, October 1, 2021

Coronary Artery Calcium Scoring to Guide Statin Therapy

A paper published in JAMA Cardiology reports on findings of a multicenter, population based, prospective study that included 1,688 participants aged 45 to 75 years with no baseline ASCVD (Atherosclerotic Vascular Disease) or diabetes  who were at intermediate risk for ASCVD and with LDL levels of 70 mg/dl.  

The authors found that among the participants with CAC scores of 0, the presence of risk-enhancing factors was not associated with overall ASCVD risk that was higher than the recommended treatment threshold for the initiation of statin therapy.  

The results of this study support the use of CAC scoring as a tool in the evaluation of risk and to more accurately classify individuals with intermediate risk for ASCVD who might benefit from statin therapy.

In conclusion the use of CAC scoring was associated with significant improvements in the reclassification and discrimination of incident ASCVD. 

Wednesday, September 1, 2021

Whole Lung Irradiation as a Novel Treatment for Covid-19 Pneumonia

A study published in ScienceDirect reports on a novel treatment of 25 patients with proven Covid-19 pneumonia.  All patients diagnosis was proven with an RT-PCR test, had SpO2 less than 94% on room air and a respiratory frequency of less than 24 per minute.  Patients were treated in accordance with standard Covid-19 guidelines and received a single fraction of low dose radiation therapy (LDRT) of 0.5 Gy to both lungs within 10 days of the onset of symptoms and/or 5 days of hospital admission.

LDRT was well tolerated by all patients.  A significant improvement in oxygenation was noted.  Demand for supplemental oxygen showed also a significant reduction in the post-RT period with 88% recovering completely with 10 days and being discharged from the hospital in 6 days.  Three patients deteriorated and died.

The authors concluded that based on their initial experience, LDRT is a promising treatment in a select group of patients with moderate to severe Covid-19 pneumonia and should be further investigated by a larger series.

Sunday, August 1, 2021

Single-view DBT and AI setup allows for effective screening mammography

A study published in Radiology determined that a single digital breast tomosynthesis (DBT) image in combination with artificial intelligence (AI) improves radiologists' productivity.

A retrospective study of 190 women with bilateral mediolateral oblique breast images that were acquired with a wide-angle DBT system was obtained.  The examination -based reader- average AUC was higher when interpreting results with AI support than when reading unaided.  The average sensitivity increased with AI support, whereas no differences in the specificity and reading time were detected.

The authors concluded that using a single-view DBT in conjunction with an AI setup could allow for more effective screening, especially in cancers detected, than using DBT alone.  

Thursday, July 1, 2021

AI-Can Reduce Workload in Breast Cancer Screening

A study published in Radiology determined that an artificial intelligence (AI) algorithm could reduce the digital breast tomosynthesis (DBT) and mammography (DM) workload of radiologists without impacting diagnostic accuracy.

A total of 15,987 DM and DBT examinations (which included 98 screening-detected and 15 interval cancers from the 15,987 women were evaluated.  In comparison with the double reading of the DBT images, AI with DBT would result in 72.5% less workload, noninferior sensitivity, and a 16.7% lower recall rate.  Similar results were obtained for AI and DM. 

AI could obviate over 70% of radiologists' double reading thus enable DBT adoption in breast cancer screening programs.

Tuesday, June 1, 2021

Cardiac MRI in the Assessment of Pulmonary Hypertension

Cardiac Magnetic Resonance Imaging (CMR) is an effective tool for evaluating patients with pulmonary arterial hypertension (PAH), according to a new meta-analysis published in JACC: Cardiovascular Imaging.

The study's authors analyzed data from 22 different studies, covering nearly 2,000 patients with pulmonary hypertension.  There were 18 clinical worsening events and 8 deaths per 100 patient-years.

The researchers determined CMR to be a powerful tool for predicting clinical worsening in PHA patients, with every 1% decrease in right ventricular ejection fraction associated with a 4.9% increase in the risk of clinical worsening over the next 22 months and a 2.1% increase in the risk of mortality over the next 54 months.

The authors concluded that CMR can effectively predict clinical worsening in PHA patients.   

Saturday, May 1, 2021

Major Increase in Telehealth during Covid-19 Pandemic

 A cohort study published in JAMA of more than 36 million individuals in the US found a dramatic increase in telehealth use during the first four months of the Covid-19 pandemic.  In this study, in-person visits decreased by 37% while telehealth visits accounted for 23% of all interactions, compared with 0.3% in 2019.  Behavioral health encounters were far more likely than medical contacts to take place virtually (46% vs 22%).  Persons living in areas with limited resources were less likely to use telehealth (27% vs 20%).  The costs also decreased by 15%.  The findings of this study are relevant to physicians, administrators, and payers regarding telehealth's potential role during the pandemic and afterward. 

Thursday, April 1, 2021

USPSTF Updated Lung Cancer Screening

 The U.S. Preventive Services Task Force (USPSTF) issued updated recommendations that were published in JAMA regarding screening of lung cancer.  Lung cancer is the leading cause of cancer deaths in the U.S., and the goal of expanded screening is to detect it early enough to cure it in more individuals at high risk as those who smoke.  Large studies have concluded that among people at high risk, annual CT scans can reduce the risk of death from cancer by up to 25%.  The expert panel recommended that individuals with a long history of smoking should begin receiving low-dose CT scans at age 50, five years earlier than the group recommended in 2013. 

Monday, March 1, 2021

Seasonal Influenza "all but vanished" in 2020

As the Covid-19 pandemic raged last year, the seasonal flu nearly became nearly extinct, according to data from the U.S. Centers for Disease Control and Prevention (CDC).  While in the 2019 flu season, the CDC reported more than 65,000 cases of influenza nationwide, in 2020 CDC reported 1,016 cases.  The high vaccination rate against the flu in 2020, combined with mask-wearing, social distancing, and hand-washing, measures that were employed to stop the spread of coronavirus, helped in preventing influenza transmission.  

The decrease occurred despite a six-fold increase in testing.  Of the 394 specimens tested since September 27, 2020 only 925 or  0.2% were positive.  In 362 (39%) Influenza A was detected and in 563 (61%) Influenza B was found.

In closing, the Ancient Greeks said "ουδέν κακόν αμιγές καλού" that translates to "every cloud has a silver lining".

Monday, February 1, 2021

The Anaphylaxis rate to Pfizer's coronavirus vaccine is low

The Center for Disease Control (CDC) announced a lower rate of severe allergic reactions in people vaccinated with the Pfizer/BioNTech coronavirus vaccine.  The CDC reported that through January 18, 2021, there were 50 cases of anaphylaxis reported in recipients of the vaccine, implying a rate of about 5 per million doses administered.  This is significantly lower than the previously reported rate of 11.1 per million doses administered through December 23, 2020.

Saturday, January 2, 2021

The Corona Virus Epoch; A Review

We just finished one of the most turbulent years of our lives, which will be remembered as the Coronavirus epoch.  We now know that nearly 84 million people in 191 countries were infected by Coronavirus in 2020.  Those infections lead to approximately 1,8 million deaths.

On March 11, 2020, the World Health Organization (WHO) declared the coronavirus outbreak a pandemic.  Soon after the WHO declared a pandemic, two prestigious institutions made predictions regarding the potential death toll different countries might experience; the Institute of Health and Evaluation ( IHME) predicted that there would be 84,000 deaths in the United States by August of 2020, while the Imperial College of London predicted 1,2 million individuals will die in the US.  Both predictions were wrong as it is difficult for mathematical models to predict the severity of a pandemic and its resultant death rate.  It is near impossible to foretell how inhabitants of different countries will adhere to preventative measures recommended by health authorities.

On December 31, 2020, the United States reported 20 million confirmed cases of Covid-19, which caused 347,000 deaths.  In the same period, there were 14 million confirmed cases and 337,000 deaths in the 27 countries forming the European Union.  An endless stream of publications both in the scientific journals and lay press have addressed the disease and how different governments responded to the challenge of one in a lifetime pandemic.  

I have been following the pandemic since it was first announced by the officials in Wuhan city, in China's Hubei province.  Therefore, I am writing this post to highlight certain aspects of the pandemic, as well as lessons learned in the past twelve months. 

Upon reviewing the impact of the pandemic in different countries, I observed that the lay press primarily focused on the number of cases and the number of deaths reported by countries around the world.  Although they are important metrics, it does not tell the whole story.  Statistics such as the number of dead per million accurately assess the severity of the disease and how the health systems of different countries dealt with the epidemic.  Although the United States leads the world in confirmed cases, several European countries record higher deaths per million than the United States (1,051).  These countries include Belgium (1,693), Italy (1,244), Spain (1,086), and the United Kingdom (1108).  Others such as France (967), Sweden ((873), Netherlands (664), Greece (465), and Germany (408) had lower death rates.  It is now understood that the high death rates in Italy (1,244) and the State of New York (1,899) were not necessarily a result of inferior health systems, but more so from overwhelming caseloads exceeding intensive care units (ICU) capacity during the first wave of the pandemic.

Although some European countries such as Germany and Greece fared relatively well, several Asian countries have proven more successful in mitigating the impact of Covid-19.  Japan had 28 deaths per million, South Korea reported 18 deaths per million, Singapore 5 deaths per million and China had 4 deaths per million.  Taiwan's 802 confirmed cases and only 7 deaths since the beginning of the pandemic corresponds to 0,3 deaths per million - a most impressive accomplishment.

Another key metric regarding how countries' health systems are coping with the pandemic is the 7-day moving average of cases and deaths per million.  In the last 7 days the deaths per million, for select countries were as follows; UK (91), Germany (80), Italy (80), US (56), Greece (50), France (40), Sweden (7), Japan (36), South Korea (4), Singapore (0), China (0), and Taiwan (0).

A brief discussion of different approaches taken by three countries in dealing with the pandemic will point to their successes and failures. 

Taiwan is an island nation of 24 million that sits just 70 miles from mainland China. It has extensive business and social contacts with Wuhan, the epicenter of the SARS-CoV-2 viral outbreak.  Therefore, it seemed inevitable that Taiwan would have been one of the severely impacted countries in the world.  So, how did Taiwan manage to have only 802 cases and only 7 deaths due to the disease?  On January 20, 2020, Taiwan activated its Central Epidemic Command Center(CECC), which rolled out several measures. First, it provided its citizens with three free masks.  Six days later, Taiwan banned travel to and from Wuhan.  A JAMA article by Wang et al explains how the CECC used big data analytics, new technology, and proactive testing to monitor and control the endemic.  More importantly, the CECC served as the central source of information to the public, with daily conferences that provided reliable and easily understood information about the outbreak.  Taiwan's impressive 0.3 deaths per million can be attributed to these measures, and the Taiwanese population's rapid adoption of simple preventive measures including masks, social distancing, and hand washing.  Interestingly, Taiwan's Infection fatality rate (IFR) of the last 7 and/or 14 days remains 0 percent, as the last patient died on May 11, 2020.

Sweden, a northern European nation of 10 million people, instituted a controversial plan, reliant upon social distancing.  Sweden allowed people to move freely - visiting restaurants, bars, and stores  - without wearing masks if they kept distant from each other.  Although not everyone in Sweden was happy with this approach, most Swedes were satisfied.  Dr. Anders Tegnell, the epidemiologist, who advocated this approach believed that enough people will become immune by June of 2020,  which would have given Sweden an advantage as most countries would have experienced a "second wave" later in the year - something that indeed happened.  He also suggested that "lockdown" strategies have no scientific basis,  especially when it comes to young adults and children as they do not transmit the disease.  Sweden experienced a second wave, but its IFR of the last 7 days is 1.1% - among the lowest in Europe.

Greece, a southern European nation of 10 million, instituted two strict "lockdowns" as the method to control the spread of the pandemic.  The first lockdown started on February 27 and the second on November 7, 2020.  During the 2 1/2 months lockdown protocol, everyone in the country had to request permission to venture outside of their houses.  Permission was granted for visiting a supermarket, a pharmacy, a doctor; or for taking a brief walk outdoors.  Approval was granted by sending and receiving an SMS from a government agency.  Those caught violating the lockdown were fined 300 euros.  In addition, a total curfew was enacted between 9 pm and 6 am.  It was due to the timely lockdowns, Greece experienced one of the lowest death rates (488) in Europe. Greece's IFR of the last 7 days of 8% suggests that its health system has been overwhelmed by the second wave of Covid-19 cases, similar to what happened in  Italy and New York during the first wave of the pandemic.

A major development in the fight against Covid-19 was the development of two mRNA vaccines by Pfizer and ModernaThe vaccines which do not contain the live virus received emergency approval by the CDC in the United States and the European Medicines Agency (EMA) in the European Union.  Since the vaccines were approved approximately 5 million people have been vaccinated in the United States.  Although this represents 1.5% of the total population, States have prioritized the vaccination of health care workers, nursing and assisted living homes' residents, individuals over the age of 75, and individuals with underlying conditions that put them at high risk of complications and/or death from the disease.  An encouraging development is the successful conclusion of the phase III trial of the Oxford vaccine and its subsequent approval by the UK Medicines and Health Products Regulatory AgencyAstraZeneca, the company that manufactures and distributes the vaccine, has initiated production and vaccinations have started in the United Kingdom.  It is expected that the Oxford vaccine, which can be stored at temperatures found in regular refrigerators, therefore it is easier to distribute, will soon be approved by the CDC in the US and by the EMA in the European Union.   

Two interesting but controversial approaches may be tried in the UK, in the near future.  The UK is currently experiencing an increase in the number of new cases and an increase in its IFR.  The first suggestion/plan is to give one dose of the vaccine(s) instead of two, as one dose is 70-80% effective.  If such a policy is employed, then twice as many individuals can be vaccinated in the next few months.  Therefore, the "herd immunity" threshold of 70% of the population could be reached earlier.  The second approach under consideration by the UK is to give the second or booster dose of a vaccine from a different company if the vaccines of the first company have been exhausted.  In the US, the Federal Government is in talks with Moderna regarding evidence from the phase II trial that two 50 microgram doses of its vaccine in individuals between the ages of 18 and 55, provides "identical immune response" to the recommended two 100 microgram doses.  Finally, in France, they decided to vaccinate all individuals over the age of 75 instead of staggering by decades such as 85 and over, 75 to 85, etc as most countries do.

It should be noted that Russia was the first country that started vaccinating its citizens with the Sputnik V vaccine, which was developed by the Gamaleya National Center for Epidemiology and Microbiology. Two hundred thousand Russians have been vaccinated as of December 14, 2020.  Israel has become the world leader in the fight against Covid-19 by procuring enough doses of Pfizer's vaccine and by vaccinating 10% of its population thus far, a true success story.  At least 150 companies around the world are developing vaccines.   Sinopharm and Sinovac in China have completed their phase III trials, and vaccination of China's 1.3 billion population has begun.  China plans to vaccinate 50 million of its citizens by mid-February.  The development of Covid-19 vaccines is a wonder of science, but the vaccines will not make Covid-19 disappear, thus people should continue preventive practices.

As of the end of 2020, the death of 346,000 individuals in the United States corresponds to a death rate of 0.1%, which is 5 to 10 times higher than the death rate from the seasonal flu.  If the vaccines prove to be 80-90% effective, as it was found on the completion of clinical trials, then the future death rate(s) experienced by the US and other countries will be similar to that of seasonal flu - provided that their population gets vaccinated.  I know this is a daring prediction, but I feel confident, that it will be the case.

In conclusion, while most people will like the complete eradication of the SARS-Cov-2 virus, it simply will not happen.  Viruses and bacteria are integral members of Earth's ecosystem and it is a hybris to advocate for their destruction.  A more reasonable approach for humans is to learn to co-exist with them and manage the deleterious effects with preventive measures.  So far, the Taiwanese have done so most successfully, and the Swedes to a lesser degree.   Wearing masks in enclosed spaces such as buses, keep social distance within reason, and employing hygienic practices such as regular hand washing, should be accepted and practiced by all.  Limited lockdowns should be utilized as measures of last resort, as it is well known that they have an adverse economic impact.  Finally, I expect the vaccine availability and usage to increase in 2021, and that medications such as dexamethasone, monoclonal antibodies, vitamin D3 will make the disease easier to control, allowing societies to return to normalcy, as we knew it.