Off-label drug use during the COVID-19 pandemic in Africa: topic modelling and sentiment analysis of ivermectin in South Africa and Nigeria as a case study.

Although rejected by the World Health Organization, the human and even veterinary formulation of ivermectin has widely been used for prevention and treatment of COVID-19. In this work we leverage Twitter to understand the reasons for the drug use from ivermectin supporters, their source of information, their emotions, their gender demographics, and location information, in Nigeria and South Africa. Topic modelling is performed on a Twitter dataset gathered using keywords 'ivermectin' and 'ivm'. A model is fine-tuned on RoBERTa to find the stance of the tweets. Statistical analysis is performed to compare the stance and emotions. Most ivermectin supporters either redistribute conspiracy theories posted by influencers, or refer to flawed studies confirming ivermectin efficacy in vitro. Three emotions have the highest intensity, optimism, joy and disgust. The number of anti-ivermectin tweets has a significant positive correlation with vaccination rate. All the provinces in South Africa and most of the provinces of Nigeria are pro-ivermectin and have higher disgust polarity. This work makes the effort to understand public discussions regarding ivermectin during the COVID-19 pandemic to help policy-makers understand the rationale behind its popularity, and inform more targeted policies to discourage self-administration of ivermectin. Moreover, it is a lesson to future outbreaks.

DRESS syndrome due to iodinated contrast media. A case report.

BACKGROUND: The most frequent non-immediate reactions described with iodinated contrast media (ICM) are mild to moderate, however, some cases of patients with severe non-immediate reactions, such as drug eruption with eosinophilia and systemic symptoms (DRESS) have been described. CASE PRESENTATION: An 84-year-old patient developed DRESS syndrome after administration of ICM ioversol. The patient fullfilled the RegiSCAR diagnostic criteria for DRESS (definite score = 6). He underwent intradermal skin testing (IDT) with the widest panel of ICM available at our center. IDT was positive with ioversol and iomeprol. A punch biopsy was performed on the positive IDT with the culprit drug (ioversol) and histopathology was compatible with a T-cell mediated mechanism. CONCLUSION: In this case, the IDT-positive biopsy was consistent with DRESS syndrome caused by T-lymphocyte activation, supporting the clinical diagnosis.

Results from the INMUNOSUN-SOGUG trial: a prospective phase II study of sunitinib as a second-line therapy in patients with metastatic renal cell carcinoma after immune checkpoint-based combination therapy.

BACKGROUND: The INMUNOSUN trial had the objective of prospectively evaluating the efficacy and safety of sunitinib as a pure second-line treatment in patients with metastatic renal cell carcinoma (mRCC) who have progressed to first-line immune checkpoint inhibitor (ICI)-based therapies. PATIENTS AND METHODS: A multicenter, phase II, single-arm, open-label study was carried out in patients with a histologically confirmed diagnosis of mRCC with a clear-cell component who had progressed to a first-line regimen of ICI-based therapies. All patients received sunitinib 50 mg once daily orally for 4 weeks, followed by a 2-week rest period following package insert instructions. The primary outcome was the objective response rate. RESULTS: Twenty-one assessable patients were included in the efficacy and safety analyses. Four patients [19.0%, 95% confidence interval (CI) 2.3% to 35.8%] showed an objective response (OR), and all of them had partial responses. Additionally, 14 (67%) patients showed a stable response, leading to clinical benefit in 18 patients (85.7%, 95% CI 70.7% to 100%). Among the four assessable patients who showed an OR, the median duration of the response was 7.1 months (interquartile range 4.2-12.0 months). The median progression-free survival (PFS) was 5.6 months (95% CI 3.1-8.0 months). The median overall survival (OS) was 23.5 months (95% CI 6.3-40.7 months). Patients who had better antitumor response to first-line ICI-based treatment showed a longer PFS and OS with sunitinib. The most frequent treatment-emergent adverse events were diarrhea (n = 11, 52%), dysgeusia (n = 8, 38%), palmar-plantar erythrodysesthesia (n = 8, 38%), and hypertension (n = 8, 38%). There was 1 patient who exhibited grade 5 pancytopenia, and 11 patients experienced grade 3 adverse events. Eight (38%) patients had serious adverse events, four of which were considered to be related to sunitinib. CONCLUSION: Although the INMUNOSUN trial did not reach the pre-specified endpoint, it demonstrated that sunitinib is active and can be safely used as a second-line option in patients with mRCC who progress to new standard ICI-based regimens.

Incidence and clinical pattern of contralateral synchronous and metachronous germ cell testicular cancer.

BACKGROUND: Incidence of a second testicular tumor is higher in patients diagnosed with testicular cancer than in the general population. As incidence of unilateral germ cell cancer is increasing worldwide and most of these patients are cured, a growing number of patients at risk of developing a contralateral testis cancer is expected. OBJECTIVE: To analyze clinical and histological characteristics, as well as the absolute and cumulative incidence of a second testicular cancer in a cohort of 3,834 patients diagnosed with germ cell testicular cancer between I/1994 and I/2018 in 18 referral hospitals of the Spanish Germ Cell Cancer Group. METHODS: Patients were treated according to stage and year of diagnoses. Contralateral testis biopsy was not routinely performed, according to European Association of Urology rules. Follow-up of the contra lateral testis consists of a physical exam only and an annual optional testicular ultrasound for 10 years. RESULTS: Median age of the patients included was 32 years (18-82). With a median follow-up of 61 months (0-240), 67/3,834 patients (1.74%) were diagnosed with a second testicular tumor. The second testicular tumor was synchronic (diagnosed within 6 months of the first orchiectomy) in 19 patients, and metachronous in 48. Pathology of the second tumor was reported as a seminomatous testis tumor in 47 patients and a nonseminomatous cancer in 20. Cumulative incidence of contralateral testicular cancer was 2% at 5 years, and 4% (IC 95% 3%-5%) at 14 years. Younger age was a risk factor for developing a second testicular tumor (P = 0.006), whereas chemotherapy reduced the risk for a metachronous testicular cancer (P = 0.046). Within our cohort, 6 families with testicular cancer aggregation (more than 2 tumors in the same family) were identified. CONCLUSIONS: Incidence of second testicular neoplasm in this cohort of 3,834 patients was similar to that which has been reported in other countries. Metachronous tumors and seminomas are more common. Follow-up of the contralateral testis is mandatory, as well as adequate information for patients to prevent a second neoplasm if feasible, and to detect and treat it as soon as possible.

Utilidad diagnóstica e impacto terapéutico de la PET/TC con [18F]F-Fluormetilcolina en la recidiva bioquímica del cáncer de próstata / Diagnostic utility and therapeutic impact of PET/CT [18F]F-Fluoromethylcholine-Choline in the biochemical recurrence of prostate cancer

OBJETIVO: Valorar la capacidad diagnóstica de la PET/TC con [18F]F-Fluormetilcolina en la recidiva bioquímica del cáncer de próstata (CP) y su impacto terapéutico. MATERIAL Y MÉTODOS: Se incluyeron 108 pacientes, diagnosticados de CP con criterios bioquímicos de recurrencia. Se realizó una PET/TC Colina mediante estudio dinámico de pelvis y estudio de cuerpo entero a los 60min postinyección del trazador. Se ha analizado la relación entre los estudios positivos y el valor del PSA clasificando a los pacientes en tres grupos (<1,2/1,2-2/>2ng/ml); se ha valorado la capacidad diagnóstica respecto a la RM pelviana y el impacto en la decisión terapéutica. RESULTADOS: Se identificó la localización de la recurrencia en 85 de 108 pacientes (78,7%): 34 local, 47 ganglionar pelviana y 58 lesiones a distancia, incluyendo ganglios retroperitoneales, mediastínicos y lesiones en órganos a distancia (hueso y pulmón). Se diagnosticaron segundos tumores en 4 pacientes. No se encontraron diferencias significativas en el porcentaje de estudios positivos dependiendo del tratamiento primario. Los pacientes con PSA>2ng/ml mostraron un porcentaje de detección de enfermedad más alto que los pacientes con un nivel de PSA inferior, con diferencias significativas (p < 0,0001). La PET/TC [18F]F-Colina fue capaz de detectar enfermedad local, no conocida previamente por la RM, en el 29,41% de los pacientes. La PET/TC Colina tuvo impacto en el manejo terapéutico en 67 de 108 pacientes (62%). CONCLUSIONES: La PET/TC [18F]F-Fluormetilcolina es una herramienta útil en la detección de enfermedad locorregional y diseminada del CP tratado con sospecha de recurrencia, proporcionando un cambio de manejo terapéutico en un 62% de los pacientes

OBJECTIVE: To assess the diagnostic capability of PET/CT with [18F]F-Fluoromethylcholine in prostate cancer (PC) with biochemical recurrence and its therapeutic impact. MATERIAL AND METHODS: We included 108 patients, diagnosed with PC with biochemical criteria for recurrence. A PET/CT Choline scan was performed by dynamic pelvic and whole body study at 60min post-tracer injection. The relationship between the positive studies and the PSA value was analysed by classifying patients into three groups (<1.2/1.2-2/>2ng/ml), and the diagnostic capacity was assessed with respect to pelvic MRI and the impact on the therapeutic decision. RESULTS: The location of recurrence was identified in 85 of 108 patients (78.7%): 34 local, 47 pelvic lymph nodes and 58 distant lesions, including retroperitoneal, mediastinal lymph nodes and distant organ lesions (bone and lung). Second tumors were diagnosed in 4 patients. No significant differences were found in the percentage of positive studies depending on primary treatment. Patients with PSA>2ng/ml showed a higher percentage of disease detection than patients with a lower PSA level, with significant differences (p < 0.0001). PET/CT [18F]F-Choline was able to detect local disease, not previously known from MRI, in 29.41% of patients. PET/CT Choline had an impact on therapeutic management in 67 of 108 patients (62%). CONCLUSIONS: PET/CT with [18F]F-Fluoromethylcholine is a useful tool in the detection of locoregional and disseminated disease of PC treated with suspicion of recurrence, providing a change in therapeutic management in 62% of patients

Diagnostic utility and therapeutic impact of PET/CT [18F]F-Fluoromethylcholine -Choline in the biochemical recurrence of prostate cancer. / Utilidad diagnóstica e impacto terapéutico de la PET/TC con [18F]F-Fluormetilcolina en la recidiva bioquímica del cáncer de próstata.

OBJECTIVE: To assess the diagnostic capability of PET/CT with [18F]F-Fluoromethylcholine in prostate cancer (PC) with biochemical recurrence and its therapeutic impact. MATERIAL AND METHODS: We included 108 patients, diagnosed with PC with biochemical criteria for recurrence. A PET/CT Choline scan was performed by dynamic pelvic and whole body study at 60min post-tracer injection. The relationship between the positive studies and the PSA value was analysed by classifying patients into three groups (<1.2/1.2-2/>2ng/ml), and the diagnostic capacity was assessed with respect to pelvic MRI and the impact on the therapeutic decision. RESULTS: The location of recurrence was identified in 85 of 108 patients (78.7%): 34 local, 47 pelvic lymph nodes and 58 distant lesions, including retroperitoneal, mediastinal lymph nodes and distant organ lesions (bone and lung). Second tumors were diagnosed in 4 patients. No significant differences were found in the percentage of positive studies depending on primary treatment. Patients with PSA>2ng/ml showed a higher percentage of disease detection than patients with a lower PSA level, with significant differences (p<0.0001). PET/CT [18F]F-Choline was able to detect local disease, not previously known from MRI, in 29.41% of patients. PET/CT Choline had an impact on therapeutic management in 67 of 108 patients (62%). CONCLUSIONS: PET/CT with [18F]F-Fluoromethylcholine is a useful tool in the detection of locoregional and disseminated disease of PC treated with suspicion of recurrence, providing a change in therapeutic management in 62% of patients.

Drug Challenge Tests With General Anesthetics: Predictive Value of Skin Tests.

BACKGROUND: The study of perioperative drug reactions remains a major challenge for both diagnosis and therapy. The lack of a standard assessment of allergy to general anesthetics and of data establishing the true value of skin tests for most drugs used in induction and maintenance of anesthesia, as well as the lack of commercially available reagents for in vitro tests, renders the study of these reactions problematic. The aims of this study were to provide a diagnostic protocol for drug challenge testing with general anesthetics, to establish an etiological diagnosis that is as specific as possible, and to determine the predictive value of skin tests. METHODS: Twenty-nine patients with perioperative drug reactions were included in the study from November 2008 to December 2018. RESULTS: We confirmed the high negative predictive value of the tests (96%-100%) in the case of propofol, rocuronium, and fentanyl. To our knowledge, this is the first study to describe drug challenge testing with general anesthetics and, therefore, to establish the true negative predictive value of skin tests, which leads to a definitive diagnosis and safer surgery. CONCLUSIONS: After assessing risks and benefits and considering the importance of this group of drugs, we conclude that drug challenge testing with general anesthetics is necessary. We propose a protocol for perioperative drug reactions that enables us to make a highly accurate etiological diagnosis with minimum risk for the patient.

Acute generalized exanthematous pustulosis due to teicoplanin

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Drug challenge tests with general anesthetics: predictive value of skin tests

BACKGROUND: The study of perioperative drug reactions remains a major challenge for both diagnosis and therapy. The lack of a standard assessment of allergy to general anesthetics and of data establishing the true value of skin tests for most drugs used in induction and maintenance of anesthesia, as well as the lack of commercially available reagents for in vitro tests, renders the study of these reactions problematic. The aims of this study were to provide a diagnostic protocol for drug challenge testing with general anesthetics, to establish an etiological diagnosis that is as specific as possible, and to determine the predictive value of skin tests. METHODS: Twenty-nine patients with perioperative drug reactions were included in the study from November 2008 to December 2018. RESULTS: We confirmed the high negative predictive value of the tests (96%-100%) in the case of propofol, rocuronium, and fentanyl. To our knowledge, this is the first study to describe drug challenge testing with general anesthetics and, therefore, to establish the true negative predictive value of skin tests, which leads to a definitive diagnosis and safer surgery. CONCLUSIONS: After assessing risks and benefits and considering the importance of this group of drugs, we conclude that drug challenge testing with general anesthetics is necessary. We propose a protocol for perioperative drug reactions that enables us to make a highly accurate etiological diagnosis with minimum risk for the patient

ANTECEDENTES: La ausencia de estandarización del estudio de alergia a anestésicos generales y ausencia de verdaderos datos sobre el valor de las pruebas cutáneas en la mayoría de los fármacos empleados en anestesia general, así como la ausencia de reactivos disponibles comercialmente para poder realizar tests in vitro, continúa suponiendo un dilema para estudiar las reacciones perianestésicas. El objetivo de este estudio fue aportar un protocolo de pruebas de provocación con anestésicos generales para poder establecer un diagnóstico etiológico lo mas especifico posible, y determinar el valor predictivo de las pruebas cutáneas. MÉTODOS: Desde noviembre de 2008 a diciembre de 2018, fueron estudiados 29 pacientes con reacciones perioperatorias a medicamentos. RESULTADOS: Con este estudio, confirmamos el alto valor predictivo negativo (VPN) de las pruebas cutáneas (96-100%) en el caso del propofol, rocuronio y fentanilo. En nuestro conocimiento, este es el primer trabajo que describe pruebas de provocación con anestésicos generales, y en aportar el verdadero VPN de las pruebas cutáneas, lo que permite llegar a un diagnóstico más definitivo, y a una mayor seguridad en futuras cirugías. CONCLUSIONES: Valorando riesgos /beneficios y considerando la importancia de este grupo de medicamentos, concluimos que las pruebas de provocación controlada con anestésicos generales, son necesarias. Proponemos un protocolo diagnóstico de las reacciones perioperatorias por fármacos, que permita alcanzar un diagnóstico etiológico lo más certero posible, con el menor riesgo para el paciente

Clinical patterns of Heparin allergy: cross-reactivity between low-molecular-weight Heparins and unfractionated Heparins

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Association between PD1 mRNA and response to anti-PD1 monotherapy across multiple cancer types.

Background: We hypothesized that the abundance of PD1 mRNA in tumor samples might explain the differences in overall response rates (ORR) observed following anti-PD1 monotherapy across cancer types. Patients and methods: RNASeqv2 data from 10 078 tumor samples representing 34 different cancer types was analyzed from TCGA. Eighteen immune-related gene signatures and 547 immune-related genes, including PD1, were explored. Correlations between each gene/signature and ORRs reported in the literature following anti-PD1 monotherapy were calculated. To translate the in silico findings to the clinical setting, we analyzed the expression of PD1 mRNA using the nCounter platform in 773 formalin-fixed paraffin embedded (FFPE) tumor samples across 17 cancer types. To test the direct relationship between PD1 mRNA, PDL1 immunohistochemistry (IHC), stromal tumor-infiltrating lymphocytes (sTILs) and ORR, we evaluated an independent FFPE-based dataset of 117 patients with advanced disease treated with anti-PD1 monotherapy. Results: In pan-cancer TCGA, PD1 mRNA expression was found strongly correlated (r > 0.80) with CD8 T-cell genes and signatures and the proportion of PD1 mRNA-high tumors (80th percentile) within a given cancer type was variable (0%-84%). Strikingly, the PD1-high proportions across cancer types were found strongly correlated (r = 0.91) with the ORR following anti-PD1 monotherapy reported in the literature. Lower correlations were found with other immune-related genes/signatures, including PDL1. Using the same population-based cutoff (80th percentile), similar proportions of PD1-high disease in a given cancer type were identified in our in-house 773 tumor dataset as compared with TCGA. Finally, the pre-established PD1 mRNA FFPE-based cutoff was found significantly associated with anti-PD1 response in 117 patients with advanced disease (PD1-high 51.5%, PD1-intermediate 26.6% and PD1-low 15.0%; odds ratio between PD1-high and PD1-intermediate/low = 8.31; P < 0.001). In this same dataset, PDL1 tumor expression by IHC or percentage of sTILs was not found associated with response. Conclusions: Our study provides a clinically applicable assay that links PD1 mRNA abundance, activated CD8 T-cells and anti-PD1 efficacy.

Acute tubulointerstitial nephritis associated with atezolizumab, an anti-programmed death-ligand 1 (pd-l1) antibody therapy.

Direct stimulation of the antitumor activity of immune system through checkpoint inhibitors (ICIs) has demonstrated efficacy in the treatment of different cancer types. The activity of these antibodies takes place in the immunological synapse blocking the binding of the negative immunoregulatory proteins, thus leading to the finalization of the immune response. Despite having a favorable toxicity profile, its mechanism of action impedes the negative regulation of the immune activity which can potentially favor autoimmune attacks to normal tissues. Renal toxicity has been described in several ICI but not with atezolizumab, an IgG1 monoclonal antibody targeting PD-L1 (programmed death ligand 1), approved by FDA as a second-line therapy for advanced urothelial carcinoma. Here we present a patient with a single kidney and metastatic renal cell carcinoma treated with atezolizumab and bevacizumab combination, with biopsy-proven acute interstitial nephritis, who had a complete resolution of renal dysfunction after steroid therapy.

Correction to: SEOM clinical guidelines for the treatment of metastatic prostate cancer (2017).

The original article shows two mistakes, which are listed here.