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The first case of the novel coronavirus infection (COVID-19) in Peru was reported on March 6, 2020. As of September 7, 2020, about 700 000 cases of COVID-19 resulting in 29,976 deaths have been confirmed by the Ministry of Health. Among COVID-19 patients with co-morbidities, type 2 diabetes mellitus (T2DM) has been recognized as a risk factor for severe disease. Patients with T2DM may experience diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic (HHS) if infected with the coronavirus 2 (SARS-CoV-2). Regular blood analysis including arterial blood gas is essential in monitoring the care of patients with T2DM infected with COVID-19. We report five cases of DKA in patients with underlying T2DM that presented with severe COVID-19 infection. Learning points COVID-19 may cause acute metabolic dysregulations in patients with T2DM. It is important to monitor basic metabolic panel (BMP) and arterial blood gases (ABGs) in patients with COVID-19 since metabolic complications can develop unexpectedly. Patients with T2DM develop an inflammatory syndrome characterized by severe insulin resistance and B cell dysfunction that can lead to DKA. Patient Demographics: Adult, Male, Female, Hispanic or Latino - Central American or South American, Peru Clinical Overview: Pancreas, Diabetes, Emergency, Infectious diseases Related Disciplines: General practice Publication Details: Unique/unexpected symptoms or presentations of a disease, March, 2021 Background In December 2019, the first case of COVID-19 was reported in Wuhan, China (1, 2). On March 11, 2020, the World Health Organization (WHO) declared the COVID-19 outbreak a global pandemic (3). COVID-19 primarily presents with upper respiratory symptoms; the symptoms may progress to pneumonia which may lead to respiratory failure and, in severe cases, death (4). Several complications related to COVID-19 have also been reported such as thrombotic events, CNS involvement, and cardiovascular complications (5, 6). A higher mortality rate and a worse clinical course have also been reported in patients with T2DM (7, 8). In addition, recent data have emerged regarding metabolic complications especially in patients with T2DM (9, 10). According to the Johns Hopkins Coronavirus Resource Center, Peru is one of the countries with a high prevalence of COVID-19 infections worldwide (11). In Peru, 683 702 cases of COVID-19 have been diagnosed resulting in 29 687 deaths reported by the National Ministry of Health. There is no exact data about how many of the total cases had Diabetes mellitus (DM). However, among those who died, approximately 43.1% had DM as a comorbidity. In Nasca, 80 deaths of 4817 cases have already been reported by the National Ministry of Health (12). This study reports 5 T2DM patients with COVID-19 presenting with DKA during an outbreak in a small city in Peru.

Summary Diabetic foot ulcer morbidity and mortality are dramatically increasing worldwide, reinforcing the urgency to propose more effective interventions to treat such a devastating condition. Previously, using a diabetic mouse model, we demonstrated that administration of bone marrow mesenchymal stem cells derivatives is more effective than the use of bone marrow mesenchymal stem cells alone. Here, we used the aforementioned treatments on three patients with grade 2 diabetic foot ulcers and assessed their beneficial effects, relative to the conventional approach. In the present study, two doses of cell derivatives, one dose of mesenchymal stem cells or one dose of vehicle (saline solution with 5% of human albumin), were intradermally injected around wounds. Wound healing process and changes on re-epithelialization were macroscopically evaluated until complete closure of the ulcers. All ulcers were simultaneously treated with conventional treatment (PolyMen® dressing). Patients treated with either cell derivatives or mesenchymal stem cells achieved higher percentages of wound closure in shorter times, relative to the patient treated with the conventional treatment. The cell derivative and mesenchymal stem cells approaches resulted in complete wound closure and enhanced skin regeneration at some point between days 35 and 42, although no differences between these two treatments were observed. Moreover, wounds treated with the conventional treatment healed after 161 days. Intradermal administration of cell derivatives improved wound healing to a similar extent as mesenchymal stem cells. Thus, our results suggest that mesenchymal stem cell derivatives may serve as a novel and potential therapeutic approach to treat diabetic foot ulcers. Learning points: In diabetic mouse models, the administration of mesenchymal stem cells derivatives have been demonstrated to be more effective than the use of marrow mesenchymal stem cells alone. Mesenchymal stem cells have been explored as an attractive therapeutic option to treat non-healing ulcers. Mesenchymal stem cells derivatives accelerate the re-epithelialization on diabetic foot ulcers.

Summary Both human immunodeficiency virus (HIV) and antiretroviral therapy (ART) are associated with endocrine dysfunction (1). The term 'immune reconstitution inflammatory syndrome' (IRIS) describes an array of inflammatory conditions that occur during the return of cell-mediated immunity following ART. Graves’ disease (GD) occurs rarely as an IRIS following ART. In this study, we describe the case of a 40-year-old Brazilian female who was diagnosed with HIV following admission with cryptococcal meningitis and salmonellosis. At this time, she was also diagnosed with adrenal insufficiency. Her CD4 count at diagnosis was 17 cells/µL which rose to 256 cells/µL over the first 3 months of ART. Her HIV viral load, however, consistently remained detectable. When viral suppression was finally achieved 21 months post diagnosis, an incremental CD4 count of 407 cells/µL over the following 6 months ensued. Subsequently, she was diagnosed with a late IRIS to cryptococcus 32 months following initial ART treatment, which manifested as non-resolving lymphadenitis and resolved with high-dose steroids. Following the initiation of ART for 45 months, she developed symptomatic Graves’ hyperthyroidism. At this time, her CD4 count had risen to 941 cells/µL. She has been rendered euthyroid on carbimazole. This case serves to remind us that GD can occur as an IRIS post ART and typically has a delayed presentation. Learning points Endocrinologists should be aware of the endocrine manifestations of HIV disease, in particular, thyroid pathology. Endocrinologists should be aware that IRIS can occur following the initiation of ART. Thyroid dysfunction can occur post ART of which Graves' disease (GD) is the most common thyroid manifestation. GD as a manifestation of ART-induced IRIS can have a delayed presentation. Infectious disease physicians should be aware of endocrine manifestations associated with HIV and ART.

Summary Anaplastic thyroid cancer (ATC) is the type of thyroid cancer that has the worst prognosis. It usually presents as a rapidly growing cervical mass that generates compressive symptoms. Its association with thyrotoxicosis is rare. A 76-year-old woman, with no contributory history, presented with a 3-month course of fast-growing cervical tumor, associated with tenderness, cough, and weight loss. Physical examination revealed goiter, localized erythema, and a painful and stone tumor dependent on the right thyroid lobe. Due to the malignant findings of the thyroid ultrasound, the patient underwent a thyroid core needle biopsy, which indicated ATC. Laboratory tests revealed leukocytosis, decreased thyroid-stimulating hormone, elevated free thyroxine (fT4), and increased thyroperoxidase (TPO) antibodies. At the beginning, we considered that the etiology of thyrotoxicosis was secondary to subacute thyroiditis (SAT) after SARS-CoV-2 infection, due to the immunochromatography result and chest tomography findings. The result of markedly elevated TPO antibodies left this etiology more remote. Therefore, we suspected Graves’ disease as an etiology; however, thyroid histopathology and ultrasound did not show compatible findings. Therefore, we suspect that the main etiology of thyrotoxicosis in the patient was the destruction of the thyroid follicles caused by a rapid invasion of malignant cells, which is responsible for the consequent release of preformed thyroid hormone. ATC is a rare endocrine neoplasm with high mortality; it may be associated with thyrotoxicosis, whose etiology can be varied; therefore, differential diagnosis is important for proper management. Learning points Anaplastic thyroid cancer is the thyroid cancer with the worst prognosis and the highest mortality. The association of anaplastic thyroid cancer with thyrotoxicosis is rare, and a differential diagnosis is necessary to provide adequate treatment. Due to the current pandemic, in patients with thyrotoxicosis, it is important to rule out SARS-CoV-2 as an etiology. Anaplastic thyroid cancer, due to its aggressive behavior and rapid growth, can destroy thyroid follicular cells, generating preformed thyroid hormone release, being responsible for thyrotoxicosis.

Summary An 8-year-old boy with cystic fibrosis came to our attention for an empty scrotum. General physical examination showed a normal penis and hypoplastic scrotum with non-palpable testes bilaterally. Routine blood investigations showed low levels of LH, testosterone, inhibin B and antiMullerian hormone and elevated levels of FSH. Karyotype was normal. An abdominal ultrasound confirmed the absence of the testes into the scrotum, in the inguinal region and abdomen. At laparoscopy were noted bilaterally hypotrophic spermatic vessels, absence of the vas deferens and a closed inner ring. Inguinal exploration found out a small residual testis and histological examination showed fibrotic tissue. This is the first case of testicular atrophy associated to CFTR mutation described. The process that led to bilateral testicular and vas deferens atrophy remains unexplained, a possible influence of CFTR dysfunction cannot be ruled out, although it is possible that these conditions are independently associated. Learning points: Cystic fibrosis produces a multisystemic disease which can affect also the reproductive tract. Nearly 97–98% of male patients are infertile because of congenital bilateral absence of vas deferens. A correlation between cystic fibrosis and bilateral testicular atrophy could be possible.

El síndrome de resistencia a la insulina tipo B (TBIR) es una enfermedad autoinmune rara causada por anticuerpos contra el receptor de insulina. Debe considerarse en pacientes con disglucemia y resistencia severa a la insulina cuando se hayan descartado otras causas más comunes. Presentamos el caso de un varón de 72 años con diabetes tipo 2 de 4 años de evolución que presentó hipercatabolismo, vitíligo, acantosis nigricans e hiperglucemia resistente a dosis masivas de insulina (hasta 1.000 U/día). La detección de anticuerpos anti-receptor de insulina confirmó TBIR. El paciente recibió seis pulsos de metilprednisolona y tratamiento diario con ciclofosfamida durante 6 meses. La respuesta al tratamiento fue evidente después del cuarto pulso de metilprednisolona, ​​como lo indica el aumento de peso, disminución de la hemoglobina glicosilada y disminución del requerimiento de insulina exógena que posteriormente se suspendió por episodios de hipoglucemia. Finalmente se logró la remisión y actualmente el paciente se encuentra asintomático, no requiere insulinoterapia, tiene glucemia normal y está a la espera de iniciar terapia de mantenimiento con azatioprina. Por lo tanto, TBIR remitió sin el uso de rituximab. Este caso destaca la importancia del diagnóstico y tratamiento oportuno, así como la importancia de las características clínicas, los hallazgos de laboratorio disponibles y la medicación. Se requieren grandes estudios controlados para estandarizar un protocolo terapéutico, particularmente en entornos con recursos limitados donde el acceso a rituximab es limitado. Type B insulin resistance syndrome (TBIR) is a rare autoimmune disease caused by antibodies against the insulin receptor. It should be considered in patients with dysglycaemia and severe insulin resistance when other more common causes have been ruled out. We report a case of a 72-year-old male with a 4-year history of type 2 diabetes who presented with hypercatabolism, vitiligo, acanthosis nigricans, and hyperglycaemia resistant to massive doses of insulin (up to 1000 U/day). Detection of anti-insulin receptor antibodies confirmed TBIR. The patient received six pulses of methylprednisolone and daily treatment with cyclophosphamide for 6 months. Response to treatment was evident after the fourth pulse of methylprednisolone, as indicated by weight gain, decreased glycosylated haemoglobin and decreased requirement of exogenous insulin that was later discontinued due to episodes of hypoglycaemia. Remission was eventually achieved and the patient is currently asymptomatic, does not require insulin therapy, has normal glycaemia and is awaiting initiation of maintenance therapy with azathioprine. Thus, TBIR remitted without the use of rituximab. This case highlights the importance of diagnosis and treatment in a timely fashion, as well as the significance of clinical features, available laboratory findings and medication. Large controlled studies are required to standardise a therapeutic protocol, particularly in resource-constrained settings where access to rituximab is limited.