Can COVID-19 impact the natural history of paracoccidioidomycosis? Insights from an atypical chronic form of the mycosis.

Paracoccidioidomycosis (PCM) is a systemic fungal infection caused by Paracoccidioides spp. It can occur as an acute/subacute form (A/SAF), a chronic form (CF) and rarely as a mixed form combining the features of the two aforementioned forms in an immunocompromised patient. Here, we report a 56-year-old male patient with CF-PCM who presented with atypical manifestations, including the development of an initial esophageal ulcer, followed by central nervous system (CNS) lesions and cervical and abdominal lymphatic involvement concomitant with severe SARS-CoV-2 infection. He was HIV-negative and had no other signs of previous immunodeficiency. Biopsy of the ulcer confirmed its mycotic etiology. He was hospitalized for treatment of COVID-19 and required supplemental oxygen in the intensive unit. The patient recovered without the need for invasive ventilatory support. Investigation of the extent of disease during hospitalization revealed severe lymphatic involvement typical of A/SAF, although the patient`s long history of high-risk exposure to PCM, and lung involvement typical of the CF. Esophageal involvement is rare in non-immunosuppressed PCM patients. CNS involvement is also rare. We suggest that the immunological imbalance caused by the severe COVID-19 infection may have contributed to the patient developing atypical severe CF, which resembles the PCM mixed form of immunosuppressed patients. Severe COVID-19 infection is known to impair the cell-mediated immune response, including the antiviral response, through T-lymphopenia, decreased NK cell counts and T-cell exhaustion. We hypothesize that these alterations would also impair antifungal defenses. Our case highlights the potential influence of COVID-19 on the course of PCM. Fortunately, the patient was timely treated for both diseases, evolving favorably.

Disseminated Kaposi Sarcoma Associated With Cytomegalovirus Proctitis in People Living With Human Immunodeficiency Virus (PLHIV): A Major Diagnostic Dilemma.

Kaposi sarcoma (KS) is a vascular tumor of low malignancy. Lesions may vary in shape, color, and size. Angiogenesis, spindle-shaped cells, and inflammatory infiltration are the main histologic features of the condition. Human herpesvirus-8 (HHV-8) infection and immune dysfunction play a key role in the development of KS. We report a case of a 40-year-old man with disseminated KS (DKS) who underwent an endoscopic examination. Colonoscopy revealed an ulcer in the anal canal. Biopsy and immunohistochemistry (IHC) confirmed the diagnosis of cytomegalovirus (CMV) proctitis, a rare and underreported pathology.

Septic shock, hyperferritinemic syndrome, and multiple organ dysfunction without respiratory failure in a patient with disseminated histoplasmosis and advanced HIV disease.

AIDS-related disseminated histoplasmosis (DH) can cause septic shock and multiorgan dysfunction with mortality rates of up to 80%. A 41-year-old male presented with fever, fatigue, weight loss, disseminated skin lesions, low urine output, and mental confusion. Three weeks before admission, the patient was diagnosed with HIV infection, but antiretroviral therapy (ART) was not initiated. On day 1 of admission, sepsis with multiorgan dysfunction (acute renal failure, metabolic acidosis, hepatic failure, and coagulopathy) was identified. A chest computed tomography showed unspecific findings. Yeasts suggestive of Histoplasma spp. were observed in a routine peripheral blood smear. On day 2, the patient was transferred to the ICU, where his clinical condition progressed with reduced level of consciousness, hyperferritinemia, and refractory septic shock, requiring high doses of vasopressors, corticosteroids, mechanical ventilation, and hemodialysis. Amphotericin B deoxycholate was initiated. On day 3, yeasts suggestive of Histoplasma spp. were observed in the bone marrow. On day 10, ART was initiated. On day 28, samples of peripheral blood and bone marrow cultures revealed Histoplasma spp. The patient stayed in the ICU for 32 days, completing three weeks of intravenous antifungal therapy. After progressive clinical and laboratory improvement, the patient was discharged from the hospital on oral itraconazole, trimethoprim-sulfamethoxazole, and ART. This case highlights the inclusion of DH in the differential diagnosis of patients with advanced HIV disease, septic shock and multiorgan dysfunction but without respiratory failure. In addition, it provides early in-hospital diagnosis and treatment and comprehensive management in the ICU as determining factors for a good outcome.

Can COVID-19 impact the natural history of paracoccidioidomycosis? Insights from an atypical chronic form of the mycosis

ABSTRACT Paracoccidioidomycosis (PCM) is a systemic fungal infection caused by Paracoccidioides spp. It can occur as an acute/subacute form (A/SAF), a chronic form (CF) and rarely as a mixed form combining the features of the two aforementioned forms in an immunocompromised patient. Here, we report a 56-year-old male patient with CF-PCM who presented with atypical manifestations, including the development of an initial esophageal ulcer, followed by central nervous system (CNS) lesions and cervical and abdominal lymphatic involvement concomitant with severe SARS-CoV-2 infection. He was HIV-negative and had no other signs of previous immunodeficiency. Biopsy of the ulcer confirmed its mycotic etiology. He was hospitalized for treatment of COVID-19 and required supplemental oxygen in the intensive unit. The patient recovered without the need for invasive ventilatory support. Investigation of the extent of disease during hospitalization revealed severe lymphatic involvement typical of A/SAF, although the patient`s long history of high-risk exposure to PCM, and lung involvement typical of the CF. Esophageal involvement is rare in non-immunosuppressed PCM patients. CNS involvement is also rare. We suggest that the immunological imbalance caused by the severe COVID-19 infection may have contributed to the patient developing atypical severe CF, which resembles the PCM mixed form of immunosuppressed patients. Severe COVID-19 infection is known to impair the cell-mediated immune response, including the antiviral response, through T-lymphopenia, decreased NK cell counts and T-cell exhaustion. We hypothesize that these alterations would also impair antifungal defenses. Our case highlights the potential influence of COVID-19 on the course of PCM. Fortunately, the patient was timely treated for both diseases, evolving favorably.

Septic shock, hyperferritinemic syndrome, and multiple organ dysfunction without respiratory failure in a patient with disseminated histoplasmosis and advanced HIV disease

ABSTRACT AIDS-related disseminated histoplasmosis (DH) can cause septic shock and multiorgan dysfunction with mortality rates of up to 80%. A 41-year-old male presented with fever, fatigue, weight loss, disseminated skin lesions, low urine output, and mental confusion. Three weeks before admission, the patient was diagnosed with HIV infection, but antiretroviral therapy (ART) was not initiated. On day 1 of admission, sepsis with multiorgan dysfunction (acute renal failure, metabolic acidosis, hepatic failure, and coagulopathy) was identified. A chest computed tomography showed unspecific findings. Yeasts suggestive of Histoplasma spp. were observed in a routine peripheral blood smear. On day 2, the patient was transferred to the ICU, where his clinical condition progressed with reduced level of consciousness, hyperferritinemia, and refractory septic shock, requiring high doses of vasopressors, corticosteroids, mechanical ventilation, and hemodialysis. Amphotericin B deoxycholate was initiated. On day 3, yeasts suggestive of Histoplasma spp. were observed in the bone marrow. On day 10, ART was initiated. On day 28, samples of peripheral blood and bone marrow cultures revealed Histoplasma spp. The patient stayed in the ICU for 32 days, completing three weeks of intravenous antifungal therapy. After progressive clinical and laboratory improvement, the patient was discharged from the hospital on oral itraconazole, trimethoprim-sulfamethoxazole, and ART. This case highlights the inclusion of DH in the differential diagnosis of patients with advanced HIV disease, septic shock and multiorgan dysfunction but without respiratory failure. In addition, it provides early in-hospital diagnosis and treatment and comprehensive management in the ICU as determining factors for a good outcome.

Post COVID-19 Disseminated Mucormycosis in a 55-year-old patient in Western Amazon: Case report

A feared fungal disease surprised and became a warning to severe cases of COVID-19, especially to health professionals involved with the pandemic. Designated as black fungus for public health services in India, where reported data reflects an increase of more than eighty times the expected increase for Rhizopus among the communities. The disease has become even more worrisome due to the high mortality already established as an opportunistic infection, coupled with the reserved prognosis for all those infected and hospitalised by the SARS-CoV-2 severity criteria. This patient, who was submitted to corticosteroid therapy, in an excessive dose, therefore immunosuppressive, developed a severe, disseminated clinical form. It was verified the progression of the lesions and thus the high risk of trans- surgical lethality, or, also, by the insufficiency of conduct in removing the lesions to their satisfaction. Thus, the therapeutic option is the associated use of micafungin, liposomal amphotericin B and isavuconazole for the regressive phase. The patient remains hospitalised with progressive and discrete improvement. Until the opportunity of reevaluation of the surgery by the interspecialty collaboration.

Uma temida doença fúngica surpreendeu e se tornou um alerta para casos graves de COVID-19, principalmente aos profissionais de saúde envolvidos com a pandemia. Designado como fungo preto para serviços de saúde pública na Índia, onde os dados relatados refletem um aumento de mais de oitenta vezes o aumento esperado para Rhizopus entre as comunidades. A doença tornou-se ainda mais preocupante devido à alta mortalidade já estabelecida como infecção oportunista, aliada ao prognóstico reservado para todos os infectados e internados pelos critérios de gravidade do SARS-CoV-2. Esse paciente, que foi submetido à corticoterapia, em dose excessiva, portanto imunossupressora, desenvolveu uma forma clínica grave e disseminada. Verificou-se a progressão das lesões e, portanto, o alto risco de letalidade transcirúrgica, ou, ainda, pela insuficiência de conduta na remoção das lesões a contento. Assim, a opção terapêutica é o uso associado de micafungina, anfotericina B lipossomal e isavuconazol para a fase regressiva. O paciente permanece internado com melhora progressiva e discreta. Até a oportunidade de reavaliação da cirurgia pela colaboração interespecialista.

Uterine cavity embryonal rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is a rare solid tumor in childhood and adolescence. The higher incidence is predominant during the first two decades of life. According to the Intergroup RMS Study Group, the embryonal RMS (ERMS), botryoidal variant, constitutes a histological subtype characterized as a "grape-like" lesion of 2.0 cm to 9.5 cm. The treatment involves chemotherapy, surgery, and/or radiotherapy. We present the case of a 14-year-old female patient diagnosed with ERMS, botryoidal variant, which originated in the uterine cervix with vaginal externalization. The initial therapeutic approach comprised an initial prolapsed mass excision followed by Wertheim­Meigs surgery due to the tumor extension. No consensual protocol to ERMS treatment is found in the medical literature; however, a combined approach seems to offer a better result. The postoperative time period was uneventful and the patient followed an adjuvant therapy with vincristine, d-actinomycin, and cyclophosphamide. A comprehensive evaluation of the therapeutic options preserving the reproductive function­unfortunately not always possible­is part of a multi-disciplined care team concerning the pediatric patients.

Uterine cavity embryonal rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is a rare solid tumor in childhood and adolescence. The higher incidence is predominant during the first two decades of life. According to the Intergroup RMS Study Group, the embryonal RMS (ERMS), botryoidal variant, constitutes a histological subtype characterized as a "grape-like" lesion of 2.0 cm to 9.5 cm. The treatment involves chemotherapy, surgery, and/or radiotherapy. We present the case of a 14-year-old female patient diagnosed with ERMS, botryoidal variant, which originated in the uterine cervix with vaginal externalization. The initial therapeutic approach comprised an initial prolapsed mass excision followed by Wertheim-Meigs surgery due to the tumor extension. No consensual protocol to ERMS treatment is found in the medical literature; however, a combined approach seems to offer a better result. The postoperative time period was uneventful and the patient followed an adjuvant therapy with vincristine, d-actinomycin, and cyclophosphamide. A comprehensive evaluation of the therapeutic options preserving the reproductive function-unfortunately not always possible-is part of a multi-disciplined care team concerning the pediatric patients.

Congenital pulmonary airway malformation

Congenital pulmonary airway malformation (CPAM) is a developmental malformation of the lower respiratory tract. We report the case of a male newborn diagnosed with cystic lung disease during prenatal ultrasound. A cesarean section was performed at the 32nd gestational week because of premature rupture of the membranes, and soon after the delivery the newborn developed respiratory failure and died. The aim of this study is to report an autopsy case because of its rarity, and to briefly discuss the CPAM subtypes and differential diagnosis of cystic lung diseases of childhood.

Congenital pulmonary airway malformation.

Congenital pulmonary airway malformation (CPAM) is a developmental malformation of the lower respiratory tract. We report the case of a male newborn diagnosed with cystic lung disease during prenatal ultrasound. A cesarean section was performed at the 32nd gestational week because of premature rupture of the membranes, and soon after the delivery the newborn developed respiratory failure and died. The aim of this study is to report an autopsy case because of its rarity, and to briefly discuss the CPAM subtypes and differential diagnosis of cystic lung diseases of childhood.

Gastric lethal hemorrhage due to Dieulafoy's disease.

Gastric Dieulafoy's lesion (DL) is a potentially fatal entity that causes upper digestive hemorrhage as a consequence of the erosion of an abnormal large-caliber artery in the submucosa of the gastrointestinal tract. We report the case of a 59-year-old female patient admitted to the emergency facility due to melena without any active sign of bleeding during the esophagogastroduodenoscopy. Unexpectedly, she progressed presenting a massive hematemesis followed by an irreversible cardiorespiratory arrest. The aim of this study is to draw attention to DL as a possible cause of massive and fatal digestive hemorrhage, and to describe the anatomical autopsy findings.

Gastric lethal hemorrhage due to Dieulafoy's disease

Gastric Dieulafoy's lesion (DL) is a potentially fatal entity that causes upper digestive hemorrhage as a consequence of the erosion of an abnormal large-caliber artery in the submucosa of the gastrointestinal tract. We report the case of a 59-year-old female patient admitted to the emergency facility due to melena without any active sign of bleeding during the esophagogastroduodenoscopy. Unexpectedly, she progressed presenting a massive hematemesis followed by an irreversible cardiorespiratory arrest. The aim of this study is to draw attention to DL as a possible cause of massive and fatal digestive hemorrhage, and to describe the anatomical autopsy findings.

Pulmonary agenesis and respiratory failure in childhood.

Pulmonary agenesis (PA) is a rare congenital anomaly, which may be unilateral or bilateral. Unilateral PA may be associated with nonspecific respiratory symptoms. We report the case of 5-month-old infant who presented a normal development until the age of 4 months when a respiratory infection caused an acute respiratory distress syndrome with a fatal outcome. The autopsy findings depicted the right lung agenesis without any other concomitant malformation. Although respiratory symptoms represent frequent complaints in pediatrics, the aim of this study is not only to draw attention to the unilateral pulmonary agenesis as a possible underlying malformation in children who present recurrent and severe respiratory symptoms, but also to report a case diagnosed at autopsy.

Primary endocardial fibroelastosis and nonimmune hydrops fetalis: case report with autopsy.

Endocardial fibroelastosis is an important cause of congestive heart failure and death in infancy and early childhood. When present, it is commonly associated with non immune hydrops fetalis. The aim of this study is to draw attention for possible cardiac abnormalities in cases of fetal hydrops, and report a case of premature death by primary endocardial fibroelastosis with autopsy.

Increased angiogenesis in primary myelofibrosis: latent transforming growth factor-ß as a possible angiogenic factor.

OBJECTIVE: The aim of this work was to demonstrate a possible relationship between anti-latency-associated peptide human latent transforming growth factor beta 1 (latent TGF-ß1) expression in megakaryocytes and microvascular density in bone marrow biopsies from patients with essential thrombocythemia and primary myelofibrosis. METHODS: Microvascular density was evaluated by immunohistochemical analysis and the expression of latent TGF-ß1 in samples (100 megakaryocytes per bone marrow sample) from 18 essential thrombocythemia and 38 primary myelofibrosis (19 prefibrotic and 19 fibrotic) patients. Six bone marrow donor biopsies were used as controls. Fibrosis in the bone marrow biopsies was evaluated according to the European Consensus. RESULTS: The average fibrosis grade differed between essential thrombocythemia and primary myelofibrosis groups when compared to the control group. Latent TGF-ß1 expression differed significantly between the fibrotic primary myelofibrosis (PMF) group and the control group (p-value<0.01). A high degree of neo-angiogenesis (demonstrated by analysis of CD34 expression) was detected in patients with myelofibrosis. There were correlations between latent TGF-ß1 expression and microvascular density (r=0.45; p-value<0.0009) and between degree of microvascular density and fibrosis grade (r=0.80; p-value<0.0001). Remarkable differences for neo-angiogenesis were not observed between patients with essential thrombocythemia and controls. CONCLUSION: Angiogenesis participates in the pathogenesis of primary myelofibrosis, in both the prefibrotic and fibrotic stages, while latent TGF-ß is differentially expressed only in the prefibrotic stage.

Increased angiogenesis in primary myelofibrosis: latent transforming growth factor-β as a possible angiogenic factor

Objective: The aim of this work was to demonstrate a possible relationship between anti-latency-associated peptide human latent transforming growth factor beta 1 (latent TGF-β1) expression in megakaryocytes and microvascular density in bone marrow biopsies from patients with essential thrombocythemia and primary myelofibrosis. Methods: Microvascular density was evaluated by immunohistochemical analysis and the expression of latent TGF-β1 in samples (100 megakaryocytes per bone marrow sample) from 18 essential thrombocythemia and 38 primary myelofibrosis (19 prefibrotic and 19 fibrotic) patients. Six bone marrow donor biopsies were used as controls. Fibrosis in the bone marrow biopsies was evaluated according to the European Consensus. Results: The average fibrosis grade differed between essential thrombocythemia and primary myelofibrosis groups when compared to the control group. Latent TGF-β1 expression differed significantly between the fibrotic primary myelofibrosis (PMF) group and the control group (p-value < 0.01). A high degree of neo-angiogenesis (demonstrated by analysis of CD34 expression) was detected in patients with myelofibrosis. There were correlations between latent TGF-β1 expression and microvascular density (r = 0.45; p-value < 0.0009) and between degree of microvascular density and fibrosis grade (r = 0.80; p-value < 0.0001). Remarkable differences for neo-angiogenesis were not observed between patients with essential thrombocythemia and controls. Conclusion: Angiogenesis participates in the pathogenesis of primary myelofibrosis, in both the prefibrotic and fibrotic stages, while latent TGF-β is differentially expressed only in the prefibrotic stage...

The relationship of the active and latent forms of TGF-ß1 with marrow fibrosis in essential thrombocythemia and primary myelofibrosis.

The aim of this study was to perform an immunohistochemical analysis from 100 megakaryocytes per sample, analyzing positivity and intensity levels of anti-LAP human TGF-ß1 (or Latent TGF-ß1) and anti-TGF-ß1 (or Active TGF-ß1) antibodies from 18 essential thrombocythemia (ET) and 38 primary myelofibrosis (PMF) patients (being 19 pre-fibrotic and 19 fibrotic). Six bone marrow donor biopsies were used as controls. Fibrosis in bone marrow biopsies (BMB) was evaluated according to the European Consensus. The average fibrosis grade differed between each group (P=0.001 or P=0.003). Latent TGF-ß1 values differed significantly between pre-fibrotic (P=0.018) and fibrotic (P=0.031) groups when compared with the control group. The high immunoexpression level of Latent TGF-ß1 in the megakaryocytes from patients with myelofibrosis, which was not observed in patients with essential thrombocythemia, may be associated with the development of bone marrow fibrosis.

MPL immunohistochemical expression as a novel marker for essential thrombocythemia and primary myelofibrosis differential diagnosis.

To evaluate the grading of fibrosis and immunohistochemical expression of MPL in bone marrow biopsies of ET and PMF. Fibrosis in bone marrow biopsies (BMBs) was evaluated according to the European Consensus for grading of fibrosis, according to reticulin proliferation. Immunohistochemical analysis was performed in samples from 18 ET and 38 PMF patients: 19 were classified as pre-fibrotic and 19 were classified as fibrotic according to the World Health Organization (WHO) criteria, by means of the MPL antibody. Six bone marrow donors' biopsies were used as controls. Average reticulin (p<0.003) and MPL (p<0.008) values differed significantly between the ET group and the pre-fibrotic stage PMF group. The MPL immunohistochemical expression may represent a new marker for differential diagnosis between ET and pre-fibrotic stage PMF.

Tumor sincrônico gástrico e colonônico: relato de caso / Gastric tumorsynchronous and colon

Racional - Para que um tumor seja considerado sincrônico deve ser excluída a possibilidade de metástase, tempo de diagnóstico entre o primeiro e o segundo tumor não deve ultrapassar seis meses. Tumores sincrônicos são relativamente raros, mas sabe-se da ocorrência simultânea dos tumores gástrico e colônico; em vista disso é prudente a conduta de se procurar o segundo tumor quando do diagnóstico do primeiro. No caso do Brasil esta...