A multicenter study of the risk of major bleeding in patients with and without cirrhosis undergoing percutaneous liver procedures.

Percutaneous liver procedures are frequently performed in patients with abnormal coagulation tests. Current guidelines suggest prophylactic transfusion is not mandatory in all patients with liver disease or cirrhosis, depending on the risk of bleeding. This study aims to describe the incidence and risk of major bleeding after percutaneous liver procedure in patients with and without cirrhosis. This retrospective study includes patients who underwent percutaneous liver biopsy and radiofrequency and microwave ablation of liver lesions at 3 centers in Spain. A transfusion protocol was considered for platelet counts <50,000 and/or international normalized ratio >1.5. The primary outcome was major bleeding. A total of 1797 patients were included in the study, with 316 having cirrhosis (18%) and 1481 without cirrhosis (82%). Among the patients with cirrhosis, 80 were classified as Child A, and percutaneous liver biopsy was the most frequent procedure (86%). Fourteen patients (0.8%) experienced major bleeding, with 0.4% occurring in radiofrequency and microwave ablation and 0.8% in percutaneous liver biopsy. Bleeding occurred in 0.6% of patients with cirrhosis compared to 0.8% in those without ( p = ns). No clinical or procedural variables were associated with bleeding. Twenty-five patients (1.4%) had an international normalized ratio >1.5, and 22 patients (1.2%) had a platelet count <50,000. Only 24% (6/25) of patients with an international normalized ratio >1.5 were transfused with fresh frozen plasma, and 72% (16/22) of those with platelet counts <50,000 received platelet transfusion. Patients with cirrhosis were more frequently transfused (5.9% vs. 1.5%). None of the patients who met the criteria for transfusion experienced major bleeding, regardless of whether they received a transfusion, and none of the patients who had a major bleeding episode met the transfusion criteria. In this cohort, major bleeding after percutaneous liver procedure occurred in <1% of patients, making it a low-risk procedure for patients with and without cirrhosis. Although not uniformly adopted, the current transfusion protocol still led to unnecessary blood product administration.

Tuberculosis in otherwise healthy adults with inherited TNF deficiency.

Severe defects in human IFNγ immunity predispose individuals to both Bacillus Calmette-Guérin disease and tuberculosis, whereas milder defects predispose only to tuberculosis1. Here we report two adults with recurrent pulmonary tuberculosis who are homozygous for a private loss-of-function TNF variant. Neither has any other clinical phenotype and both mount normal clinical and biological inflammatory responses. Their leukocytes, including monocytes and monocyte-derived macrophages (MDMs) do not produce TNF, even after stimulation with IFNγ. Blood leukocyte subset development is normal in these patients. However, an impairment in the respiratory burst was observed in granulocyte-macrophage colony-stimulating factor (GM-CSF)-matured MDMs and alveolar macrophage-like (AML) cells2 from both patients with TNF deficiency, TNF- or TNFR1-deficient induced pluripotent stem (iPS)-cell-derived GM-CSF-matured macrophages, and healthy control MDMs and AML cells differentiated with TNF blockers in vitro, and in lung macrophages treated with TNF blockers ex vivo. The stimulation of TNF-deficient iPS-cell-derived macrophages with TNF rescued the respiratory burst. These findings contrast with those for patients with inherited complete deficiency of the respiratory burst across all phagocytes, who are prone to multiple infections, including both Bacillus Calmette-Guérin disease and tuberculosis3. Human TNF is required for respiratory-burst-dependent immunity to Mycobacterium tuberculosis in macrophages but is surprisingly redundant otherwise, including for inflammation and immunity to weakly virulent mycobacteria and many other infectious agents.

Autoantibodies Neutralizing GM-CSF in HIV-Negative Colombian Patients Infected with Cryptococcus gattii and C. neoformans.

BACKGROUND: Cryptococcosis is a life-threatening disease caused by Cryptococcus neoformans or C. gattii. Neutralizing autoantibodies (auto-Abs) against granulocyte-macrophage colony-stimulating factor (GM-CSF) in otherwise healthy adults with cryptococcal meningitis have been described since 2013. We searched for neutralizing auto-Abs in sera collected from Colombian patients with non-HIV-associated cryptococcosis in a retrospective national cohort from 1997 to 2016. METHODS: We reviewed clinical and laboratory records and assessed the presence of neutralizing auto-Abs against GM-CSF in 30 HIV negative adults with cryptococcosis (13 caused by C. gattii and 17 caused by C. neoformans). RESULTS: We detected neutralizing auto-Abs against GM-CSF in the sera of 10 out of 13 (77%) patients infected with C. gattii and one out of 17 (6%) patients infected with C. neoformans. CONCLUSIONS: We report eleven Colombian patients diagnosed with cryptococcosis who had auto-Abs that neutralize GM-CSF. Among these patients, ten were infected with C. gattii and only one with C. neoformans.

MRI Using Gadoxetic Acid in the Work-Up of Liver Nodules Not Conclusively Benign in Budd-Chiari Syndrome: A Prospective Long-Term Follow-Up.

Introduction: The incidence of hepatocellular carcinoma (HCC) in Budd-Chiari syndrome (BCS) is unknown and there is no validated diagnostic work-up to define the liver nodules with arterial phase hyperenhancement (APHE), suggesting malignancy. This prospective study evaluates HCC incidence in a Western cohort of patients with BCS and assesses the performance of MRI with hepatobiliary contrast (HB-MRI) for nodule characterization. Methods: Patients with BCS followed in our hospital were prospectively evaluated by MRI with extracellular contrast (EC-MRI). Nodules with APHE categorized as non-conclusively benign by 2 radiologists were studied by HB-MRI and reviewed by 2 radiologists blinded to the EC-MRI results. A new EC-MRI 1 year later and clinical, analytical, and sonographic follow-up every 6 months for a median of 10 years was performed. Results: A total of 55 non-conclusively benign nodules with APHE were detected at EC-MRI in 41 patients. While 32 of them were suggestive of HCC by EC-MRI, all the 55 nodules showed increased uptake of hepatobiliary contrast. An unequivocal central scar was seen in 12/55 nodules at HB-MRI regardless of it was not detected on the EC-MRI. None of the nodules was hypointense in the hepatobiliary phase (HBP). HCC was not detected during a median of 10 years of follow-up. Conclusions: Detection of nodules with APHE is frequent in patients with BCS, but HCC is rare in Western patients with BCS. While EC-MRI may detect nodules suggesting malignancy, the identification of contrast uptake in the HBP at HB-MRI may help categorize them as benign.

Infradesnivel del segmento ST y neumotórax espontáneo izquierdo / ST-segment depression and left spontaneous pneumothorax

RESUMEN El neumotórax espontáneo es una entidad poco frecuente, y es poco frecuente su asociación con los cambios electrocardiográficos. En estos casos, las anormalidades más frecuentes son la elevación del segmento ST, la inversión de la onda T y la pobre progresión de la onda R en derivaciones precordiales. Presentamos el caso de un varón de 25 años quien presentó un neumotórax espontáneo izquierdo, a su ingreso el paciente tuvo un electrocardiograma con infradesnivel en el segmento ST en derivaciones inferiores, hallazgos que resolvieron posterior al tratamiento del neumotórax con una toracotomía.

ABSTRACT Spontaneous pneumothorax is a rare entity, and its association with electrocardiographic changes is infrequent. In these cases, the most frequent abnormalities are ST-segment elevation, T-wave inversion and poor R wave progression in precordial leads. We present the case of a 25-year-old man who experienced a left spontaneous pneumothorax secondary to a subpleural bleb. Upon admission, his electrocardiogram revealed ST-segment depression in the inferior leads and aVF. These findings resolved following management of pneumothorax through thoracotomy.

Autoantibodies neutralizing GM-CSF in HIV-negative Colombian patients infected with Cryptococcus gattii and C. neoformans.

Background: Cryptococcosis is a life-threatening disease caused by Cryptococcus neoformans or C. gattii. Autoantibodies (auto-Abs) neutralizing granulocyte-macrophage colony-stimulating factor (GM-CSF) in otherwise healthy adults with cryptococcal meningitis have been described since 2013. We searched for neutralizing auto-Abs in sera from Colombian patients with non-HIV related cryptococcosis in a retrospective national cohort collected from 1997 to 2016. Methods: We reviewed clinical and laboratory records and assessed the presence of neutralizing auto-Abs in 30 HIV (-) adults presenting cryptococcosis (13 by C. gattii, and 17 by C. neoformans). Results: We detected auto-Abs neutralizing GM-CSF in the plasma of 9 out of 13 (69%) patients infected with C. gattii and 1 out of 17 (6%) patients with C. neoformans. Conclusions: We report ten Colombian patients with cryptococcosis due to auto-Abs neutralizing GM-CSF. Nine of the ten patients were infected with C. gattii, and only one with C. neoformans.

Intoxicación severa por 3,4-metilendioximetanfetamina (MDMA). Reporte de caso

La intoxicación por 3,4-metilendioximetanfetamina (MDMA), ha tenido un dramático resurgimiento desde 1980, se ha extendido por gran parte de los Estados Unidos, Europa y América, ha sido ampliamente utilizada como drogas con fines recreativos, actualmente Las catinonas sintéticas se venden como "euforizantes legales" para eludir las leyes existentes, lo que resulta en toxicidad grave y muertes. Presentamos un caso clínico de un adulto joven, quien debuto con intoxicación aguda severa MDMA, con falla multiorgánica, el cual se realizó atención y manejo agudo de la intoxicación en el servicio de urgencias, con posterior manejo de complicaciones en la unidad de cuidados intensivo y finalmente con sobrevida a pesar del mal pronóstico.

3,4-methylenedioxymethamphetamine (MDMA) intoxication, has had a dramatic resurgence since 1980, has spread throughout much of the United States, Europe and America, has been widely used as a recreational drug, currently Synthetic cathinones are they sell as "legal highs" to circumvent existing laws, resulting in severe toxicity and deaths. We present a clinical case of a young adult, who debuted with severe acute MDMA poisoning, with multiple organ failure, who underwent care and acute management of the poisoning in the emergency department, with subsequent management of complications in the intensive care unit and finally with survival despite the poor prognosis.

Anti-GM-CSF Neutralizing Autoantibodies in Colombian Patients with Disseminated Cryptococcosis.

BACKGROUND: Cryptococcosis is a potentially life-threatening fungal disease caused by encapsulated yeasts of the genus Cryptococcus, mostly C. neoformans or C. gattii. Cryptococcal meningitis is the most frequent clinical manifestation in humans. Neutralizing autoantibodies (auto-Abs) against granulocyte-macrophage colony-stimulating factor (GM-CSF) have recently been discovered in otherwise healthy adult patients with cryptococcal meningitis, mostly caused by C. gattii. We hypothesized that three Colombian patients with cryptococcal meningitis caused by C. neoformans in two of them would carry high plasma levels of neutralizing auto-Abs against GM-CSF. METHODS: We reviewed medical and laboratory records, performed immunological evaluations, and tested for anti-cytokine auto-Abs three previously healthy HIV-negative adults with disseminated cryptococcosis. RESULTS: Peripheral blood leukocyte subset levels and serum immunoglobulin concentrations were within the normal ranges. We detected high levels of neutralizing auto-Abs against GM-CSF in the plasma of all three patients. CONCLUSIONS: We report three Colombian patients with disseminated cryptococcosis associated with neutralizing auto-Abs against GM-CSF. Further studies should evaluate the genetic contribution to anti-GM-CSF autoantibody production and the role of the GM-CSF signaling pathway in the immune response to Cryptococcus spp.

A factorial experiment grounded in the multiphase optimization strategy to promote viral suppression among people who inject drugs on the Texas-Mexico border: a study protocol.

BACKGROUND: People who inject drugs living with HIV (PWIDLH) suffer the lowest rates of HIV viral suppression due to episodic injection drug use and poor mental health coupled with poor retention in HIV care. Approximately 44% of PWIDLH along the US-Mexico border are retained in care and only 24% are virally suppressed. This underserved region faces a potential explosion of transmission of HIV due to highly prevalent injection drug use. This protocol describes an optimization trial to promote sustained viral suppression among Spanish-speaking Latinx PWIDLH. METHODS: The multiphase optimization strategy (MOST) is an engineering-inspired framework for designing and building optimized interventions and guides this intervention. The primary aim is to conduct a 24 factorial experiment in which participants are randomized to one of 16 intervention conditions, with each condition comprising a different combination of four behavioral intervention components. The components are peer support for methadone uptake and persistence; behavioral activation therapy for depression; Life-Steps medication adherence counseling; and patient navigation for HIV care. Participants will complete a baseline survey, undergo intervention, and then return for 3-,6-,9-, and 12-month follow-up assessments. The primary outcome is sustained viral suppression, defined as viral loads of < 40 copies per mL at 6-,9-, and 12-month follow-up assessments. Results will yield effect sizes for each component and each additive and interactive combination of components. The research team and partners will make decisions about what constitutes the optimized multi-component intervention by judging the observed effect sizes, interactions, and statistical significance against real-world implementation constraints. The secondary aims are to test mediators and moderators of the component-to-outcome relationship at the 6-month follow-up assessment. DISCUSSION: We are testing well-studied and available intervention components to support PWIDLH to reduce drug use and improve their mental health and engagement in HIV care. The intervention design will allow for a better understanding of how these components work in combination and can be optimized for the setting. TRIAL REGISTRATION: This project was registered at clinicaltrials.gov (NCT05377463) on May 17th, 2022.

Lesión hepática inducida por consumo de Valeriana officinalis y Passiflora incarnata, reporte de caso / Hepatic injury induced by the consumption of Valeriana officinalis and Passiflora incarnata, a case report

Los medicamentos homeopáticos y fitoterapéuticos que contienen productos herbarios son cada vez más utilizados, sin embargo, se desconoce el potencial de efectos adversos por parte de los usuarios y personal sanitario. Se reporta el caso de una mujer de 34 años quien consulta por dolor abdominal y náuseas, con alteraciones al ingreso de función hepática con patrón hepatocelular, se descartaron múltiples etiologías y se consideró que pudiera ser lesión hepática medicamentosa secundaria al consumo de medicamentos desde hacía una semana para dismenorrea, y a fitoterapéuticos que consumía de forma crónica, los cuales se suspendieron. A los doce días de su egreso, reingresó por sintomatología similar; se documentó nuevamente perfil hepático con patrón hepatocelular. Al reinterrogatorio, la paciente comentó la ingesta crónica de Valeriana officinalis y Passiflora incarnata, que retomó al egreso hospitalario, por lo que luego de descartar diagnósticos diferenciales, se consideró que el cuadro era inducido por el consumo de dichos medicamentos. Durante la hospitalización se suspendió su consumo, con normalización del perfil hepático. Es importante que los consumidores estén informados sobre los riesgos potenciales de los productos herbarios, sus efectos por consumos prolongados y las implicaciones de la autoformulación.

Homeopathic and phytotherapeutic medicines containing herbal products are increasingly used, however the potential for adverse effects on users and healthcare personnel is unknown. We report the case of a 34-year-old woman who consulted for abdominal pain and nausea, accompanied by hepatocellular pattern on liver function tests. Multiple etiologies were ruled out and it was considered that it could be a drug-induced liver injury secondary to the consumption of medications she had been taking a week prior for dysmenorrhea, and phytotherapeutics that she had been taking for seve-ral years, which were all discontinued. Twelve days after her discharge, she was readmitted due to similar symptoms; a liver profile with a hepatocellular pattern was again documented. Upon further questioning, the patient mentioned a chronic intake of Valeriana officinalis and Passiflora incarnata, which she resumed upon discharge. After ruling out the differential diagnoses, it was concluded that the symptoms of the patient were induced by the consumption of these herbal products. During hos-pitalization, their consumption was suspended, with normalization of the liver profile. It is important that consumers are informed about the potential risks of herbal products, their effects from long-term use, and the implications of self-medication.

Gestión mSalud para la atención pacientes con Covid-19 / mHealth management for patient care with COVID-19

El SARS-CoV-2, ha tenido un gran impacto en la salud humana a nivel mundial, infectando a un gran número de personas y causando enfermedades graves. Durante el comienzo de la pandemia de Covid-19 no había la existencia de alguna cura o vacuna designada, la única forma conocida de romper la cadena de infección era el autoaislamiento y el mantenimiento del distanciamiento físico. Por lo tanto, con la finalidad de conocer y hacer un seguimiento para la correcta gestión y atención a los pacientes con Covid­19, las nuevas herramientas tecnológicas han cobrado un importante papel que ha permitido mejorar la atención en salud con respecto a la enfermedad y ayudar a evitar los contagios, así como favorecer a un buen pronóstico y progresión positiva de la enfermedad. Por medio de la revisión de publicaciones científicas actuales se ha podido observar la amplia implementación de diferentes apps para agilizar el reconocimiento, detección y diagnóstico oportuno de pacientes que contraen esta enfermedad, como la aplicación de rastreo de contacto, reconocimiento facial, Chatbot, APP para radiografías de tórax­Covid, dispositivo móvil basado en IoT, entre otros. Todas estas nuevas tecnologías presentan un importante impacto socioepidemiologico en las regiones a través de la disminución de la mortalidad, permitir el distanciamiento físico, detección oportuna, seguimiento geográfico y mapeo epidemiológico, reducción de los tiempos de espera y control de la propagación del covid; permitiendo a los sistemas de salud organizarse y prepararse mejor para futuras pandemias y así evitar el colapso de las redes de salud(AU)

SARS-CoV-2 has had a great impact on human health worldwide, infecting large numbers of people and causing serious illness. During the early days of the COVID-19 pandemic there was no designated cure or vaccine, the only known way to break the chain of infection was self-isolation and maintaining physical distancing. Therefore, in order to know and follow up for the correct management and care of patients with COVID - 19, the new technological tools have played an important role that has allowed improving health care regarding the disease and help avoid contagion, as well as favor a good prognosis and positive progression of the disease. Through the review of current scientific publications, it has been possible to observe the wide implementation of different apps to expedite the recognition, detection and timely diagnosis of patients who contract this disease, such as the application of contact tracing, facial recognition, Chatbot, APP for chest x-rays ­ Covid, IoT-based mobile device, among others. All these new technologies have a significant socio-epidemiological impact in the regions by reducing mortality, allowing physical distancing, timely detection, geographic monitoring and epidemiological mapping, reduction of waiting times and control of the spread of covid; allowing health systems to better organize and prepare for future pandemics and thus avoid the collapse of health networks(AU)

Second Adjuvant Radioiodine Therapy after Reoperation for Locoregionally Persistent or Recurrent Papillary Thyroid Carcinoma.

Introduction Differentiated thyroid carcinoma (DTC) has increased incidence. Intermediate- and high-risk patients have lymph node relapse rate ranging from 10 to 50%, and receive multiple reinterventions, increasing the morbidity of the disease. Currently, there are no established guidelines for the use of second radioactive iodine (RAI) therapy after the reintervention for local recurrence. Materials and Methods This is a retrospective review of the medical records of 1,299 patients treated from January 2016 to July 2019 with DTC. We included 48 patients who received total thyroidectomy, RAI remnant ablation, surgery to remove the locally recurrent/persistent papillary thyroid carcinoma (PTC), and received a second RAI therapy. Results There were no significant differences between thyroglobulin (Tg) levels before reoperation (Tg0), Tg levels postoperatively (Tg1), and Tg levels after 6 months of second adjuvant RAI therapy (Tg2). However, we evidenced a 69.79% drop in first Tg levels (Tg0: 24.7 vs. Tg1: 7.56, p =0.851) and 44.4% decrease in second Tg levels (Tg1: 7.56 vs. Tg2: 4.20, p =0.544). Also, 77.1% of the patients did not have another documented recurrence. The median relapse-free time was 10.9 months (range: 1.3-58.2 months). Conclusion The results of the study cannot assess that a second RAI treatment after reoperation for locoregionally persistent or recurrent disease have a significant impact on treatment outcomes in intermediate- or high-risk patients with PTC. However, the 77.1% of patients have not presented a second documented recurrence and the median values of Tg and TgAb levels showed a substantial decrease after surgery and second RAI treatment.

Replaced right hepatic artery arising from the distal renal artery, a new variation.

PURPOSE: Arterial irrigation of the liver is highly variable and widely studied due to its importance in the correct planification of the surgical or endovascular treatment of the hepatobilary area. Various classifications have been published of the common and uncommon anatomic variations of the hepatic arterial distribution. While the classic anatomic pattern of the proper hepatic artery-when it originates from the celiac trunk dividing into left and right branches-represents 50-83% of the described patterns, there are numerous uncommon distributions based on the presence of replaced or accessory hepatic arteries. In this article, we present a case of a replaced right hepatic artery originating from the right distal renal artery. METHODS: Contrast enhanced computed tomography (CECT) examination was performed on a 67 years-old male patient with compensated alcoholic cirrhosis as part of the disease monitoring. RESULTS: The replaced right hepatic artery of the patient arises from the right distal renal artery and-after its cranial course-enters the porta hepatis posterior to the main portal vein. After giving off the cystic artery, it irrigates the right hepatic lobe. The left hepatic artery does not show any variation. CONCLUSION: We present CT angiography images of an extremely rare anatomic variation of the hepatic arterial irrigation in a cirrhotic patient.

Liver Hydatid Cyst Rupture with Respiratory Distress During COVID-19 Pandemic.

We present a case of a young male patient who was brought to the emergency room with abdominal pain, fever, dyspnea and hypoxemia, and was initially oriented as an acute COVID-19 pneumonia. A thoracoabdominal computed tomography (CT) was performed to rule out pneumonia and the abdominal extension of the study revealed a hepatic hydatid cyst with rupture into the abdominal cavity with respiratory distress secondary to an anaphylactic reaction that, if left untreated, may lead to a fatal outcome. An urgent laparotomy was performed with cyst resection. The follow-up and complications are briefly described.

Uso de Antibióticos y Resistencia Antimicrobiana en la Unidad de Cuidado Intensivo Neonatal / Use of antibiotics and antimicrobial resistance in the Neonatal Intensive Care Unit

Resumen La sepsis neonatal constituye una de las principales causas de mortalidad neonatal en los países en desarrollo. Los neonatos, en particular los prematuros, tienen un mayor riesgo de infecciones bacterianas, por lo que el manejo con antibióticos constituye la terapia más frecuente en la Unidad de Cuidado Intensivo Neonatal (UCIN), estimándose en hasta un 70%. La presentación clínica de la sepsis neonatal es inespecífica en muchas ocasiones, lo que hace que la antibioticoterapia empírica se inicie tempranamente para evitar consecuencias deletéreas para los pacientes; su inespecificidad la caracteriza como un reto diagnóstico, por lo que diferentes autores han diseñado estrategias para determinar neonatos candidatos a terapia antimicrobiana. La microbiología permanece en contacto estrecho con la clínica ya que conocer los gérmenes frecuentemente asociados a la sepsis neonatal ayuda a determinar el espectro antibiótico a usar. De igual forma, el conocimiento de la farmacología antibiótica es clave puesto que el tratamiento antibiótico no es inocuo y puede asociarse a aumento de morbilidad o mortalidad. El tiempo de evolución y los factores de riesgo maternos están asociados a los gérmenes responsables esperados, ya descritos por múltiples estudios descriptivos a nivel mundial. El uso indiscriminado de antibióticos de amplio espectro para el manejo de infecciones en los recién nacidos ha generado un aumento en la resistencia antibiótica, lo que a su vez lleva a tasas más altas de fallo terapéutico con el uso de las terapias antibióticas empíricas. A razón de lo anterior, los Programas de Vigilancia de Uso de Antibióticos juegan un papel determinante para monitorear el cambio en la resistencia a nivel local para ajustar y homogeneizar la práctica médica que logre regular el uso de antibióticos y mitigar la emergente resistencia bacteriana.

Abstract Neonatal sepsis constitutes one of the main causes of neonatal mortality in developing countries. Newborns, particularly premature newborns, have a higher risk of bacterial infections that result in frequent administration of antibiotics in the Neonatal Intensive Care Units (NICU), which is estimated to be as high as 70%. The clinical presentation of neonatal sepsis is nonspecific, prompting the early use of empirical antibiotic prescription to avoid adverse consequences in the patients. Its non-specificity characterizes it as a challenging diagnostic, this aspect led several authors to design strategies to determine which newborns are true candidates for antimicrobial therapy. Microbiology is closely linked to clinical practice. Thus, knowing the most frequent bacteria associated with neonatal sepsis will be closely related to the antibiotic spectrum that should be used to treat it. Furthermore, knowledge on basic pharmacology is key inasmuch as the antimicrobial treatment is not innocuous and can be related to an increase in mortality and morbidity. Clinical course and maternal risk factors are associated with the expected responsible germs that are already described in multiple descriptive studies worldwide. Indiscriminate use of broad-spectrum antibiotics for the management of newborn infections is leading to antibiotic resistance increase. At the same time, this is related to even higher rates of therapeutic failure with empiric antimicrobial treatment. Based on this, Antimicrobial Stewardship Programs play a determinant role to monitor the changes in local resistance to adjust and homogenize medical practice to regulate the use of antibiotics and mitigate the emergent and threatening antimicrobial bacterial resistance.

The role of contrast enhanced ultrasound in the differential diagnosis of segmental testicular infarction.

A 43-year-old male presented to the emergency department with acute left testicular pain. Physical exam showed a tender left testicle and epididymis with mild swelling. Doppler and contrast enhanced ultrasound revealed a heterogeneous, avascular lesion with hyper vascularized surrounding. Follow-up contrast enhanced ultrasound performed a few days later showed persistence of the sparsely vascularized lesion with more hypoechoic echo structure. Despite the tumor markers being negative, a necrotic tumor could not be ruled out and a left orchiectomy was performed. Pathology report described an extensive segmental testicular infarction with no evidence of malignant tissue. We present the ultrasound and pathology findings, differential diagnostic pearls and clinical perspective of segmental testicular infarction.

X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19.

Autosomal inborn errors of type I IFN immunity and autoantibodies against these cytokines underlie at least 10% of critical COVID-19 pneumonia cases. We report very rare, biochemically deleterious X-linked TLR7 variants in 16 unrelated male individuals aged 7 to 71 years (mean: 36.7 years) from a cohort of 1,202 male patients aged 0.5 to 99 years (mean: 52.9 years) with unexplained critical COVID-19 pneumonia. None of the 331 asymptomatically or mildly infected male individuals aged 1.3 to 102 years (mean: 38.7 years) tested carry such TLR7 variants (p = 3.5 × 10-5). The phenotypes of five hemizygous relatives of index cases infected with SARS-CoV-2 include asymptomatic or mild infection (n=2, 5 and 38 years), or moderate (n=1, 5 years), severe (n=1, 27 years), or critical (n=1, 29 years) pneumonia. Two boys (aged 7 and 12 years) from a cohort of 262 male patients with severe COVID-19 pneumonia (mean: 51.0 years) are hemizygous for a deleterious TLR7 variant. The cumulative allele frequency for deleterious TLR7 variants in the male general population is < 6.5x10-4 We also show that blood B cell lines and myeloid cell subsets from the patients do not respond to TLR7 stimulation, a phenotype rescued by wild-type TLR7 The patients' blood plasmacytoid dendritic cells (pDCs) produce low levels of type I IFNs in response to SARS-CoV-2. Overall, X-linked recessive TLR7 deficiency is a highly penetrant genetic etiology of critical COVID-19 pneumonia, in about 1.8% of male patients below the age of 60 years. Human TLR7 and pDCs are essential for protective type I IFN immunity against SARS-CoV-2 in the respiratory tract.

What is the role of ultrasonography in the early diagnosis of scaphoid fractures?

Scaphoid fractures are the most prevalent type of carpal bone fractures. High-spatial-resolution sonography detects direct signs of scaphoid fractures such as scaphoid cortical disruption; nevertheless, indirect signs such as radiocarpal effusion and scapho-trapezium-trapezoid effusion can also be visible. The diagnosis is performed when both direct and indirect signs of scaphoid fracture are presented. The presence of indirect signs alone is not enough to complete the diagnosis, for which more advanced imaging modalities are usually required. Here, we review the anatomy of the scaphoid, the clinical manifestations of scaphoid fractures, as well as ultrasonographic findings and differential diagnosis.