Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults.

BACKGROUND: Therapies to interrupt the progression of early coronavirus disease 2019 (Covid-19) remain elusive. Among them, convalescent plasma administered to hospitalized patients has been unsuccessful, perhaps because antibodies should be administered earlier in the course of illness. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older adult patients within 72 hours after the onset of mild Covid-19 symptoms. The primary end point was severe respiratory disease, defined as a respiratory rate of 30 breaths per minute or more, an oxygen saturation of less than 93% while the patient was breathing ambient air, or both. The trial was stopped early at 76% of its projected sample size because cases of Covid-19 in the trial region decreased considerably and steady enrollment of trial patients became virtually impossible. RESULTS: A total of 160 patients underwent randomization. In the intention-to-treat population, severe respiratory disease developed in 13 of 80 patients (16%) who received convalescent plasma and 25 of 80 patients (31%) who received placebo (relative risk, 0.52; 95% confidence interval [CI], 0.29 to 0.94; P = 0.03), with a relative risk reduction of 48%. A modified intention-to-treat analysis that excluded 6 patients who had a primary end-point event before infusion of convalescent plasma or placebo showed a larger effect size (relative risk, 0.40; 95% CI, 0.20 to 0.81). No solicited adverse events were observed. CONCLUSIONS: Early administration of high-titer convalescent plasma against SARS-CoV-2 to mildly ill infected older adults reduced the progression of Covid-19. (Funded by the Bill and Melinda Gates Foundation and the Fundación INFANT Pandemic Fund; Dirección de Sangre y Medicina Transfusional del Ministerio de Salud number, PAEPCC19, Plataforma de Registro Informatizado de Investigaciones en Salud number, 1421, and ClinicalTrials.gov number, NCT04479163.).

Coronavirus Disease 2019 Convalescent Plasma Outpatient Therapy to Prevent Outpatient Hospitalization: A Meta-Analysis of Individual Participant Data From 5 Randomized Trials.

BACKGROUND: Outpatient monoclonal antibodies are no longer effective and antiviral treatments for coronavirus disease 2019 (COVID-19) disease remain largely unavailable in many countries worldwide. Although treatment with COVID-19 convalescent plasma (CCP) is promising, clinical trials among outpatients have shown mixed results. METHODS: We conducted an individual participant data meta-analysis from outpatient trials to assess the overall risk reduction for all-cause hospitalizations by day 28 in transfused participants. Relevant trials were identified by searching Medline, Embase, medRxiv, World Health Organization COVID-19 Research Database, Cochrane Library, and Web of Science from January 2020 to September 2022. RESULTS: Five included studies from 4 countries enrolled and transfused 2620 adult patients. Comorbidities were present in 1795 (69%). The virus neutralizing antibody dilutional titer levels ranged from 8 to 14 580 in diverse assays. One hundred sixty of 1315 (12.2%) control patients were hospitalized, versus 111 of 1305 (8.5%) CCP-treated patients, yielding a 3.7% (95% confidence interval [CI], 1.3%-6.0%; P = .001) absolute risk reduction and 30.1% relative risk reduction for all-cause hospitalization. The hospitalization reduction was greatest in those with both early transfusion and high titer with a 7.6% absolute risk reduction (95% CI, 4.0%-11.1%; P = .0001) accompanied by at 51.4% relative risk reduction. No significant reduction in hospitalization was seen with treatment >5 days after symptom onset or in those receiving CCP with antibody titers below the median titer. CONCLUSIONS: Among outpatients with COVID-19, treatment with CCP reduced the rate of all-cause hospitalization and may be most effective when given within 5 days of symptom onset and when antibody titer is higher.

COVID-19 Convalescent Plasma Outpatient Therapy to Prevent Outpatient Hospitalization: A Meta-analysis of Individual Participant Data From Five Randomized Trials.

Background: Monoclonal antibody and antiviral treatments for COVID-19 disease remain largely unavailable worldwide, and existing monoclonal antibodies may be less active against circulating omicron variants. Although treatment with COVID-19 convalescent plasma (CCP) is promising, randomized clinical trials (RCTs) among outpatients have shown mixed results. Methods: We conducted an individual participant data meta-analysis from all outpatient CCP RCTs to assess the overall risk reduction for all-cause hospitalizations by day 28 in all participants who had transfusion initiated. Relevant trials were identified by searching MEDLINE, Embase, MedRxiv, WHO, Cochrane Library, and Web of Science from January 2020 to September 2022. Results: Five included studies from four countries enrolled and transfused 2,620 adult patients. Comorbidities were present in 1,795 (69%). The anti-Spike or virus neutralizing antibody titer range across all trials was broad. 160 (12.2%) of 1315 control patients were hospitalized, versus 111 (8.5%) of 1305 CCP-treated patients, yielding a 3.7% (95%CI: 1.3%-6.0%; p=.001) ARR and 30.1% RRR for all-cause hospitalization. The effect size was greatest in those with both early transfusion and high titer with a 7.6% ARR (95%CI: 4.0%-11.1%; p=.0001) accompanied by at 51.4% RRR. No significant reduction in hospitalization was seen with treatment > 5 days after symptom onset or in those receiving CCP with antibody titers below the median titer. Conclusions: Among outpatients with COVID-19, treatment with CCP reduced the rate of all-cause hospitalization. CCP may be most effective when given within 5 days of symptom onset and when antibody titer is higher. Key Points: While the outpatient COVID-19 randomized controlled trial meta-analysis indicated heterogeneity in participant risk factors and convalescent plasma, the combined CCP efficacy for reducing hospitalization was significant, improving with transfusion within 5 days of symptom onset and high antibody neutralization levels.

Asymptomatic COVID-19 in the elderly: dementia and viral clearance as risk factors for disease progression.

BACKGROUND: SARS-CoV-2 infected individuals ≥60 years old have the highest hospitalization rates and represent >80% fatalities. Within this population, those in long-term facilities represent >50% of the total COVID-19 related deaths per country. Among those without symptoms, the rate of pre-symptomatic illness is unclear, and potential predictors of progression for symptom development are unknown. Our objective was to delineate the natural evolution of asymptomatic SARS-CoV-2 infection in elders and identify determinants of progression. METHODS: We established a medical surveillance team monitoring 63 geriatric institutions. When an index COVID-19 case emerged, we tested all other eligible asymptomatic elders ≥75 or >60 years old with at least 1 comorbidity. SARS-CoV-2 infected elders were followed for 28 days. Disease was diagnosed when any COVID-19 manifestation occurred. SARS-CoV-2 load at enrollment, shedding on day 15, and antibody responses were also studied. RESULTS: After 28 days of follow-up, 74/113(65%) SARS-CoV-2-infected elders remained asymptomatic. 21/39(54%) pre-symptomatic patients developed hypoxemia and ten pre-symptomatic patients died(median day 13.5,IQR 12). Dementia was the only clinical risk factor associated with disease(OR 2.41(95%CI=1.08, 5.39). In a multivariable logistic regression model, dementia remained as a risk factor for COVID-19 severe disease. Furthermore, dementia status showed a statistically significant different trend when assessing the cumulative probability of developing COVID-19 symptoms(log-rank p=0.027). On day 15, SARS-CoV-2 was detectable in 30% of the asymptomatic group while in 61% of the pre-symptomatic(p=0.012). No differences were observed among groups in RT-PCR mean cycle threshold at enrollment(p=0.391) and in the rates of antibody seropositivity(IgM and IgG against SARS-CoV-2 nucleocapsid protein). CONCLUSIONS: In summary, 2/3 of our cohort of SARS-CoV-2 infected elders from vulnerable communities in Argentina remained asymptomatic after 28 days of follow-up with high mortality among those developing symptoms. Dementia and persistent SARS-CoV-2 shedding were associated with progression from asymptomatic to symptomatic infection.

¿Cómo individualizar el tratamiento de la hipertensión arterial en las personas con diabetes mellitus tipo 2? / How to individualize arterial hypertension treatment in type 2 diabetes mellitus?

En las personas con diabetes mellitus (DM) e hipertensión arterial (HTA), los objetivos de presión arterial (PA) deben individualizarse considerando el riesgo cardiovascular, los potenciales efectos adversos de los fármacos antihipertensivos, y el costo y las preferencias de los pacientes. En personas con DM y elevado riesgo cardiovascular un objetivo de PA <130/80 mmHg sería apropiado si puede lograrse con seguridad. Si el riesgo cardiovascular es bajo, tratar la HTA con un objetivo <140/90 mmHg. En embarazadas con DM gestacional (DMG) e HTA preexistente, se sugiere un objetivo de PA de 110-135/85 mmHg con la finalidad de reducir el riesgo de eclampsia y minimizar el retraso de crecimiento intrauterino.

In patients with diabetes mellitus (DM) and hypertension (HP), blood pressure (BP) goals should be individualized considering cardiovascular risk, potential adverse effects of antihypertensive medications, cost, and patient preferences. In people with DM and high cardiovascular risk, a BP target <130/80 mmHg would be appropriate if it can be achieved safely. If cardiovascular risk is low, treat hypertension with a target <140/90 mmHg. In pregnant women with gestational diabetes mellitus (GDM) and preexisting hypertension, a BP target of 110-135/85 mmHg is suggested to reduce the risk of eclampsia and minimize intrauterine growth restriction.

¿Cómo individualizar el tratamiento de la hipertensión arterial en las personas con diabetes mellitus tipo 2? / How to individualize arterial hypertension treatment in type 2 diabetes mellitus?

En las personas con diabetes mellitus (DM) e hipertensión arterial (HTA), los objetivos de presión arterial (PA) deben individualizarse considerando el riesgo cardiovascular, los potenciales efectos adversos de los fármacos antihipertensivos, y el costo y las preferencias de los pacientes. En personas con DM y elevado riesgo cardiovascular un objetivo de PA <130/80 mmHg sería apropiado si puede lograrse con seguridad. Si el riesgo cardiovascular es bajo, tartar la HTA con un objetivo <140/90 mmHg. En embarazadas con DM gestacional (DMG) e HTA preexistente, se sugiere un objetivo de PA de 110-135/85 mmHg con la finalidad de reducir el riesgo de eclampsia y minimizar el retraso de crecimiento intrauterino.

In patients with diabetes mellitus (DM) and hypertension (HP), blood pressure (BP) goals should be individualized considering cardiovascular risk, potential adverse effects of antihypertensive medications, cost, and patient preferences. In people with DM and high cardiovascular risk, a BP target <130/80 mmHg would be appropriate if it can be achieved safely. If cardiovascular risk is low, treat hypertension with a target <140/90 mmHg. In pregnant women with gestational diabetes mellitus (GDM) and preexisting hypertension, a BP target of 110-135/85 mmHg is suggested to reduce the risk of eclampsia and minimize intrauterine growth restriction.

Neurofibromatosis elefantiásica: presentación de dos casos / Neurofibromatosis elephantiasica: report of 2 cases

La neurofibromatosis elefantiásica (NFE) es una entidad escasamente descrita. Se caracteriza por la presencia de neurofibromas plexiformes gigantes cuyas localizaciones más frecuentes son las extremidades, cuero cabelludo, cuello y hombros. Presentamos dos casos de NFE con importante compromiso de cadera y abdomen que les ocasionaba principalmente trastornos psicosociales, incluyendo dificultades en el uso de vestimenta. Se realiza una actualización del tema

Metástasis cutánea sobre cicatriz por carcinoma de esófago en acondroplásica: comunicación de un caso diagnosticado por punción aspiración con aguja fina / Cutaneous metastasis on a scar secondary to esophageal carcinoma in an achondroplasic patient: diagnosis by needle aspiration biopsy

Las metástasis cutáneas son infrecuentes y excepcionalmente provienen de esófago. Muy rara vez asientan sobre una cicatriz o son signo de presentación de un cáncer oculto. Describimos una metástasis cutánea como signo de presentación de cáncer epidermoide de esófago en una anciana acondroplásica. El diagnóstico fue realizado por punción aspiración por aguja fina (PAAF) de la lesión cutánea. Se discute el valor de la PAAF como un método rápido y válido para el diagnóstico de metástasis cutáneas. Asimismo se remarca que la ocurrencia de carcinoma de esófago y acondroplasia en una misma paciente probablemente sea una coincidencia más que una asociación