Ruxolitinib as a treatment strategy for SARS-CoV-2 pneumonia: clinical experience in a real-world setting.

INTRODUCTION: Severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) infection is characterised by a viral phase and a severe pro-inflammatory phase. The inhibition of the JAK/STAT pathway limits the pro-inflammatory state in moderate to severe COVID-19. METHODOLOGY: We analysed the data obtained by an observational cohort of patients with SARS-CoV-2 pneumonia treated with ruxolitinib in 22 hospitals of Mexico. The applied dose was determined based on physician's criteria. The benefit of ruxolitinib was evaluated using the 8-points ordinal scale developed by the NIH in the ACTT1 trial. Duration of hospital stay, changes in pro-inflammatory laboratory values, mortality, and toxicity were also measured. RESULTS: A total of 287 patients were reported at 22 sites in Mexico from March to June 2020; 80.8% received ruxolitinib 5 mg BID and 19.16% received ruxolitinib 10 mg BID plus standard of care. At beginning of treatment, 223 patients were on oxygen support and 59 on invasive ventilation. The percentage of patients on invasive ventilation was 53% in the 10 mg and 13% in the 5 mg cohort. A statistically significant improvement measured as a reduction by 2 points on the 8-point ordinal scale was described (baseline 5.39 ± 0.93, final 3.67± 2.98, p = 0.0001). There were 74 deaths. Serious adverse events were presented in 6.9% of the patients. CONCLUSIONS: Ruxolitinib appears to be safe in COVID-19 patients, with clinical benefits observed in terms of decrease in the 8-point ordinal scale and pro-inflammatory state. Further studies must be done to ensure efficacy against mortality.

All-cause mortality among patients treated with repurposed antivirals and antibiotics for COVID-19 in Mexico City: A real-world observational study.

The aim of our study was to evaluate all-cause mortality risk in patients with laboratory-confirmed COVID-19 in Mexico City treated with repurposed antivirals and antibiotics. This real-world retrospective cohort study contemplated 395,343 patients evaluated for suspected COVID-19 between February 24 and September 14, 2020 in 688 primary-to-tertiary medical units in Mexico City. Patients were included with a positive RT-PCR for SARS-CoV-2; those receiving unspecified antivirals, excluded; and groups of antivirals prescribed in < 30 patients, eliminated. Survival and mortality risks were determined for patients receiving antivirals, antibiotics, both, or none. We assessed the effect of early (<2 days) versus late (>2 days) use of antivirals on mortality in a sub-cohort of patients. Multivariable adjustment, propensity score matching, generalized estimating equations, and calculation of E-values were performed to limit confounding. 136,855 patients were analyzed; mean age 44.2 (SD:16.8) years; 51.3 % were men. 16.6 % received antivirals (3 %), antibiotics (10 %), or both (3.6 %). Antivirals studied were Oseltamivir (n=8414), Amantadine (n=319), Lopinavir-Ritonavir (n=100), Rimantadine (n=61), Zanamivir (n=39), and Acyclovir (n=36). Survival with antivirals (73.7 %, p<0.0001) and antibiotics (85.8 %, p<0.0001) was lower than no antiviral/antibiotic (93.6 %). After multivariable adjustment, increased risk of death occurred with antivirals (HR=1.72, 95 % CI: 1.61-1.84) in ambulatory (HR=4.7, 95 % CI: 3.94-5.62) and non-critical (HR=2.03, 95 % CI: 1.86-2.21) patients. Oseltamivir increased mortality risk in the general population (HR=1.72, 95 % CI: 1.61-1.84), ambulatory (HR=4.79, 95 % CI: 4.01-5.75), non-critical (HR=2.05, 95 % CI: 1.88-2.23), and pregnancy (HR=8.35, 95 % CI: 1.77-39.30); as well as hospitalized (HR=1.13, 95 % CI: 1.01-1.26) and critical patients (HR=1.22, 95 % CI: 1.05-1.43) after propensity score-matching. Early versus late oseltamivir did not modify the risk. Antibiotics were a risk factor in general population (HR=1.13, 95 % CI: 1.08-1.19) and pediatrics (HR=4.22, 95 % CI: 2.01-8.86), but a protective factor in hospitalized (HR=0.81, 95 % CI: 0.77-0.86) and critical patients (HR=0.67, 95 % CI: 0.63-0.72). No significant benefit for repurposed antivirals was observed; oseltamivir was associated with increased mortality. Antibiotics increased mortality risk in the general population but may increase survival in hospitalized and critical patients.

Treatment-Related Mortality From Infectious Complications in an Acute Leukemia Clinic.

BACKGROUND: The main causes of mortality in patients with acute leukemia are the infectious complications. The author wanted to know the induction-related mortality and treatment-related mortality in the acute leukemia patients at the Instituto Nacional de Cancerologia (INCan), Mexico. Also the author is interested in finding out the micro-organism and the main site of infection to make some changes in the management of patients in these clinics. Primary objective was induction chemotherapy-related mortality and treatment-related mortality. Secondary objective was to determine the site of infection, micro-organism, type of chemotherapy related with more mortality and relapse mortality. METHODS: This was a retrospective case-series analysis of all patients who were admitted to the INCan Acute Leukemia Clinic between January 2012 and December 2015 with febrile neutropenic complications. We reviewed the case histories of all patients, including those with acute lymphoblastic leukemia (ALL), acute myeloblastic leukemia (AML), acute biphenotypic leukemia and acute promyelocytic leukemia, regardless of disease status (newly diagnosed or relapsed) at the time of clinic attendance. Patients who died as the result of an infectious complication during the analysis window were identified, and their demographics, disease characteristics, treatment history (chemotherapy within 45 days of date of death) and details of the infectious complication resulting in death were collected. RESULTS: Of the 313 patients studied during that time period, 84 (27%) died as a result of infectious complications. Lung infections were the most common, accounting for 67% of all deaths from infectious complications. Escherichia coli producing extended-spectrum beta-lactamases was the most frequently isolated infectious organism (12 patients; 14%). The majority of deaths occurred during either induction therapy (27 patients; 32%) or treatment for a first relapse (25 patients; 30%). Hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone (hyper-CVAD) was the chemotherapy regimen most commonly received within 45 days prior to death (17 patients; 20%). CONCLUSIONS: Our findings suggest a need for long-term management and supportive care to prevent infectious complication-associated fatalities during both initial chemotherapy and subsequent disease relapse in patients with acute leukemia. The use of prophylaxis will help patients to prevent complications.

Molecular characterization and pathogenicity determination of hypervirulent Klebsiella pneumoniae clinical isolates serotype K2 in Mexico.

Hypervirulent Klebsiella pneumoniae have been rarely described in Latin America. This work describes the characterization of hypervirulent K. pneumoniae isolates capsular serotype K2 belonging to sequence types 86 and 380. The assays showed the hypervirulent K. pneumoniae highly virulent, which is determined by the plasmid borne virulence genes. At this time, the hypervirulent K. pneumoniae clinical isolates in Mexico are extensively susceptible to antibiotics.

Recomendaciones latinoamericanas para el manejo de la hipertensión arterial en adultos (RELAHTA 2)

RESUMEN Se presenta la segunda parte de las recomendaciones latinoamericanas para el manejo de la Hipertensión Arterial (HTA) en adultos. En una primera fase se han descripto los aspectos más relevantes de la epidemiología, aspectos fisiopatológicos, cómo hacer diagnóstico, pautas terapéuticas, urgencias y emergencias hipertensivas, poblaciones especiales, hipertensión refractaria y la aplicación de las guías en la vida real. En esta segunda parte, se emiten recomendaciones respondiendo a preguntas específicas para prevención primaria, secundaria, terciaria y cuaternaria. En general pocas recomendaciones al respecto del manejo de la hipertensión arterial surgen desde la clínica médica/ medicina interna, a pesar de dos situaciones: la mayoría de los pacientes con hipertensión arterial son evaluados y manejados por los clínicos, y la clínica médica es la especialidad que permite la mirada holística e integrada de los problemas de salud del adulto, permitiendo agregar el enfoque biográfico al biológico, comprender e interpretar no solo el problema de salud sino sus causas y consecuencias (que muchas veces suelen corresponder a diferentes parénquimas, lo cual en el modelo fragmentado haría transitar al paciente por distintas especialidades). El bajo porcentaje de pacientes hipertensos controlados obliga a todos los profesionales involucrados en el manejo de los mismos a optimizar recursos y detectar problemas que se asocien a un control deficitario como la sub utilización del tratamiento farmacológico, baja tasa de pacientes tratados con estrategia combinada (la mayoría de los pacientes actualmente recibe monoterapia), falta de prescripción adecuada de los cambios en el estilo de vida, baja adherencia terapéutica e inercia clínica. En la presente publicación se presentan recomendaciones efectuadas por especialistas en clínica médica / medicina interna para el manejo de la hipertensión arterial en adultos, respondiendo preguntas de prevención primaria, secundaria, terciaria, y cuaternaria.

ABSTRACT The second part of the Latin American recommendations for the management of Arterial Hypertension (HTA) in adults is presented. In a first phase, the most relevant aspects of epidemiology, physiopathological aspects, how to diagnose, therapeutic guidelines, hypertension emergencies, special populations, refractory hypertension and the application of guides in real life have been described. In this second part, recommendations are issued answering specific questions for primary, secondary, tertiary and quaternary prevention. In general, few recommendations regarding the management of arterial hypertension arise from the medical clinic / internal medicine, despite two situations: the majority of patients with hypertension are evaluated and managed by the clinicians, and the medical clinic is the specialty that allows the holistic and integrated look of the health problems in adults, allowing to add the biographical approach to the biological, to understand and interpret not only the health problem but its causes and consequences (which often correspond to different parenchyma, which in the fragmented model would make the patient move through different specialties). The low percentage of controlled hypertensive patients forces all the professionals involved in the management of them to optimize resources and detect problems that are associated with a deficit control such as the under utilization of pharmacological treatment, low rate of patients treated with combined strategy (the most patients currently receive monotherapy), lack of adequate prescription of changes in lifestyle, low therapeutic adherence and clinical inertia. This publication presents recommendations made by specialists in medical clinic/internal medicine for the management of hypertension in adults, answering primary, secondary, tertiary and quaternary prevention questions.

Nocardia transvalensis Disseminated Infection in an Immunocompromised Patient with Idiopathic Thrombocytopenic Purpura.

Nocardia transvalensis complex includes a wide range of microorganisms with specific antimicrobial resistance patterns. N. transvalensis is an unusual Nocardia species. However, it must be differentiated due to its natural resistance to aminoglycosides while other Nocardia species are susceptible. The present report describes a Nocardia species involved in an uncommon clinical case of a patient with idiopathic thrombocytopenic purpura and pulmonary nocardiosis. Microbiological and molecular techniques based on the sequencing of the 16S rRNA gene allowed diagnosis of Nocardia transvalensis sensu stricto. The successful treatment was based on trimethoprim-sulfamethoxazole and other drugs. We conclude that molecular identification of Nocardia species is a valuable technique to guide good treatment and prognosis and recommend its use for daily bases diagnosis.

PAX8 is transcribed aberrantly in cervical tumors and derived cell lines due to complex gene rearrangements.

The transcription factor PAX8, a member of the paired box-containing gene family with an important role in embryogenesis of the kidney, thyroid gland and nervous system, has been described as a biomarker in tumors of the thyroid, parathyroid, kidney and thymus. The PAX8 gene gives rise to four isoforms, through alternative mRNA splicing, but the splicing pattern in tumors is not yet established. Cervical cancer has a positive expression of PAX8; however, there is no available data determining which PAX8 isoform or isoforms are present in cervical cancer tissues as well as in cervical carcinoma-derived cell lines. Instead of a differential pattern of splicing isoforms, we found numerous previously unreported PAX8 aberrant transcripts ranging from 378 to 542 bases and present in both cervical carcinoma-derived cell lines and tumor samples. This is the first report of PAX8 aberrant transcript production in cervical cancer. Reported PAX8 isoforms possess differential transactivation properties; therefore, besides being a helpful marker for detection of cancer, PAX8 isoforms can plausibly exert differential regulation properties during carcinogenesis.

Mucormycosis in a Non-Hodgkin Lymphoma Patient Caused by Syncephalastrum racemosum: Case Report and Review of Literature.

Mucormycosis is a rare opportunistic fungal infection caused by saprophytic zygomycetes. These fungal infections are caused by members of the mucorales. The clinical importance of zygomycosis, an emerging and frequently fatal mycotic disease, has increased during recent years, due to several risk factors such as (a) the use of broad-spectrum antibiotic, (b) use of empirical antifungal treatment (mainly triazoles), and (c) aggressive chemotherapy and sustained leucopenia (i.e., peripheral stem cell transplantation). An almost fulminant pneumonia caused by Syncephalastrum racemosum in an immunocompromised patient with an aggressive non-Hodgkin lymphoma (NHL) is described. Despite treatment with amphotericin B, deoxycholate, caspofungin, and surgical resection of fungal bodies from both lungs, and survival of 10 months without relapsing from fungal infection, the patient died due to hematological complications from an unresponsive disease. Herein is the description of the first case of pulmonary infection caused by Syncephalastrum racemosum.

Catheter-related septic thrombophlebitis of the great central veins successfully treated with low-dose streptokinase thrombolysis and antimicrobials.

BACKGROUND: Septic thrombophlebitis is an iatrogenic life-threatening disease associated with use of central venous devices and intravenous (IV) therapy. In cancer patients receiving chemotherapy, vein resection or surgical thrombectomy in large central venous lines is time-consuming, can delay administration of chemotherapy, and therefore can compromise tumor control. Experience with thrombolysis has been published for catheter-related thrombosis but for septic thrombosis, this experience is scarce. RESULTS: We describe three patients with cancer and septic thrombophlebitis of central veins caused by Staphylococcus aureus treated with catheter removal, thrombolysis, and intravenous (IV) antibiotics. In our reported cases, an initial bolus of 250,000 international units (IU) of streptokinase administered during the first h followed by an infusion of 20,000-40,000 IU/h for 24-36 h through a proximal peripheral vein was sufficient to dissolve the thrombus. After thrombolysis and parenteral antibiotic for 4-6 weeks the septic thrombosis due to Staphylococcus aureus solved in all cases. No surgical procedure was needed, and potential placement of a catheter in the same vein was permitted. CONCLUSION: Thrombolysis with streptokinase solved symptoms, cured infection, prevented embolus, and in all cases achieved complete thrombus lysis, avoiding permanent central-vein occlusion.