COVID 19 y embarazo en Chile: Informe preliminar del estudio multicéntrico GESTACOVID / COVID-19 and pregnancy in Chile: preliminary report of the GESTACOVID multicenter study

INTRODUCCIÓN: En Chile, los efectos maternos y perinatales de la pandemia por SARS-CoV-2 son aún desconocidos. GESTACOVID es un estudio multicéntrico que incluye embarazadas y puérperas hasta el día 42 con COVID-19. El objetivo de este estudio es presentar un informe preliminar, describiendo el impacto de la enfermedad en las embarazadas, factores de riesgo asociados y resultados perinatales. MÉTODOS: Estudio de cohorte descriptivo que incluye 661 pacientes enroladas entre el 7 de marzo y el 6 de julio de 2020, en 23 centros hospitalarios del país. Se analizaron variables demográficas, comorbilidades, características clínicas y del diagnóstico de COVID-19 y resultado materno y perinatal. RESULTADOS: Las pacientes hospitalizadas por COVID-19 tuvieron mayor prevalencia de hipertensión arterial crónica [10% vs 3%; OR=3,1 (1,5-6,79); p=0,003] y de diabetes tipo 1 y 2 [7% vs 2%; OR=3,2 (1,3-7,7); p=0,009] que las pacientes manejadas ambulatoriamente. Un IMC >40 kg/mt2 se asoció con un riesgo dos veces mayor de requerir manejo hospitalizado [OR=2,4 (1,2 - 4,6); p=0,009]. Aproximadamente la mitad de las pacientes (54%) tuvo un parto por cesárea, y un 8% de las interrupciones del embarazo fueron por COVID-19. Hasta la fecha de esta publicación, 38% de las pacientes continuaban embarazadas. Hubo 21 PCR positivas en 316 neonatos (6,6%), la mayoría (17/21) en pacientes diagnosticadas por cribado universal. CONCLUSIONES: Las embarazadas con COVID-19 y comorbilidades como diabetes, hipertensión crónica y obesidad mórbida deben ser manejadas atentamente y deberán ser objeto de mayor investigación. La tasa de transmisión vertical requiere una mayor evaluación para diferenciar el mecanismo y tipo de infección involucrada.

INTRODUCTION: In Chile, effects of the SARS-CoV-2 infection in pregnant women are unknown. GESTACOVID is a multicenter collaborative study including pregnant women and those in the postpartum period (until 42 days) who have had COVID-19. The purpose of this study is to report our preliminary results describing the clinical impact of COVID-19 in pregnant women, the associated risk factors and perinatal results. METHODS: Descriptive cohort study including 661 patients between April 7th and July 6th, 2020, in 23 hospitals. Demographical, comorbidities, clinical and diagnostic characteristics of COVID-19 disease and maternal and perinatal outcomes were analyzed. RESULTS: Pregnant women with COVID-19 admitted to the hospital were more likely to have chronic hypertension [10% vs 3%; OR=3.1 (1.5-6.79); p=0,003] and diabetes type 1 and 2 [7% vs 2%; OR=3.2 (1.3-7.7); p=0.009] than those with outpatient management. A body mass index of >40 kg/mt2 was associated with two-fold higher risk of hospitalization [OR=2.4 (1.2-4.6); p=0.009]. Almost half of patients (54%) were delivered by cesarean section, and 8% of the medically indicated deliveries were due to COVID-19. So far, 38% of the patients are still pregnant. Among 316 newborns, there were 21 positive PCR tests (6.6%), mostly from asymptomatic mothers undergoing universal screening. CONCLUSIONS: Pregnant women with COVID-19 and comorbidities such as diabetes, chronic hypertension and morbid obesity need a close follow up and should be a matter for further research. Vertical transmission of COVID-19 should be thoroughly studied to define the mechanisms and type of infection involved.

[Rare retrovesical tumor manifestation of cystic echinococcosis (Echinococcus granulosus)]. / Seltene retrovesikale Tumormanifestation der zystischen Echinokokkose (Echinococcus granulosus).

Unclear pelvic retrovesical intraperitoneal tumors can be caused by cystic echinococcosis. A definitive diagnosis of this disease is highly problematic und often requires a qualified histological/parasitological assessment. It is not possible to diagnose or exclude a cystic echinococcosis purely on the basis of a serological diagnosis. A multiple organ infection can be excluded using CT diagnostics as described in this case. The Robert Koch Institute has to be notified in the case of a positive result.

Severe exacerbation of chronic hepatitis B after emergence of lamivudine resistance in a cirrhotic patient: immediate switch to adefovir dipivoxil appears to be indicated.

INTRODUCTION: Lamivudine is a treatment option for the therapy of chronic hepatitis B with an excellent safety profile. Unfortunately, viral resistance to lamivudine is common in the course of therapy. The lamivudine resistant mutants are usually less pathogenic than the wild type, but development of viral resistance can also lead to acute exacerbation of the underlying hepatitis. The recently FDA approved nucleoside analogue adefovir dipivoxil has potent antiviral activity against lamivudine-resistant mutants and can prevent viral replication effectively. CASE REPORT: A 31-year-old man with pre-existing compensated liver cirrhosis developed resistance to lamivudine therapy leading to subacute liver failure. After referral adefovir dipivoxil 10 mg daily was initiated within an early access protocol. Since initiating therapy with adefovir dipivoxil progression of the subacute liver failure was delayed accompanied by a rapid decrease of ALT and decline of HBV viral load. Even so, the clinical course was not reverted but showed slower deterioration. This enabled the patient to undergo living-related liver transplantation. Adefovir dipivoxil was well tolerated in the acute phase of the disease and did not cause nephrotoxicity or favour the development of hepatorenal syndrome. CONCLUSION: Adefovir dipivoxil resulted in a delay of hepatic decompensation and enabled liver transplantation as final treatment option for this patient. Earlier initiation might even have prevented the need of liver transplantation. Thus, in patients with pre-existing liver cirrhosis an early switch to adefovir dipivoxil appears indicated after emergence of lamivudine resistance.

Direct comparison of the potency of three novel cAMP analogs to induce CREB-phophorylation in rat pinealocytes.

A modified analog of cyclic adenosine 3',5'-monophosphate (cAMP), Sp-adenosine-3',5'-monophosphorothioate, designed to be highly membrane-permeable and resistant towards phosphodiesterases was found to induce the phosphorylation of the cAMP-regulated transcription factor cyclic AMP-responsive element binding protein in cultured rat pinealocytes more efficiently than previously described cAMP analogs.

(Rp)- and (Sp)-8-piperidino-adenosine 3',5'-(cyclic)thiophosphates discriminate completely between site A and B of the regulatory subunits of cAMP-dependent protein kinase type I and II.

8-Piperidino-cAMP has been shown to bind with high affinity to site A of the regulatory subunit of cAMP-dependent protein kinase type I (AI) whereas it is partially excluded from the homologous site (AII) of isozyme II [Ogreid, D., Ekanger, R., Suva, R. H., Miller, J. P., and Døskeland, S. O. (1989), Eur. J. Biochem. 181, 19-31]. To further increase this selectivity, the (Rp)- and (Sp)-diastereoisomers of 8-piperidino-cAMP[S] were synthesized and analyzed for their potency to inhibit binding of [3H]cAMP to site A and site B from type I (rabbit skeletal muscle) and type II (bovine myocardium) cAMP-dependent protein kinases. (Sp)-8-Piperidino-cAMP[S] showed an enhanced relative affinity for site AI, thus being by far the best A-selective compound (more than 100-fold) tested for this isozyme. In contrast, the (Rp)-isomer was less selective for AI than 8-Piperidino-cAMP itself. The reduction in affinities for BII, compared to 8-piperidino-cAMP, were 10-fold and 50-fold for the (Sp)- and (Rp)-isomer, respectively. Both isomers were almost completely excluded from AII, with affinities about 1000-fold lower than 8-piperidino-cAMP itself. The (Rp)-isomer selected BII with an affinity about 10,000 times higher than for AII, whereas the (Sp)-isomer showed a preference of about 70,000-fold in favour of BII. 8-Piperidino-cAMP as well as its (Sp)-isomer activated both types of holoenzyme protein kinases whereas the (Rp)-isomer acted as an antagonist of cAMP-induced activation. The study concludes that the combination of piperidino- and exocyclic sulfur substitutions generate cAMP analogs that completely discriminate between site A and B of cAMP-dependent protein kinases.

Chloramine-T effect on sodium conductance of neuroblastoma cells as studied by whole-cell clamp and single-channel analysis.

Patch-clamp experiments were done on sodium channels of neuroblastoma cells (N1E-115) in the presence of tetraethylammonium ions to block potassium channels. In Ringer solution whole-cell records revealed a diphasic INa inactivation with the fast (tau 0) component. being clearly larger than the slow (tau 1 approximately 3 tau 0) component. In single-channel studies on inside-out patches the mean open time, to, turned out to be only a fraction of tau 0 and almost independent of membrane potential. After external application of chloramine-T INa inactivation of whole cells was delayed with both tau 0 and tau 1 increased, and incomplete, i.e. a persistent current component emerged. The latter was maximal at a more positive membrane potential than the peak current. Also, after chloramine-T treatment the peak INa increased, particularly at weak depolarizations. In inside-out patches the equally effective internal application of chloramine-T led to bursting channel openings with mean burst times (tb) approximately 6 ms, and gap times (tg) approximately 20 ms, where gap is defined as a closure of greater than or equal to 1.5 ms. Within the bursts to was approximately 2 ms, again clearly shorter than tau 0; the mean close time, tc was approximately 0.5 ms. The single-channel conductance was approximately 13 pS and unaffected by chloramine-T. Diphasic INa inactivation and the fact that to less than tau 0 led to an extension of the model of Aldrich and Stevens [J Neurosci 7:418-431 (1987)], in which overall kinetics is determined by the openings rather than closures of the sodium channels.(ABSTRACT TRUNCATED AT 250 WORDS)