Granulomatosis With Polyangiitis Presenting With Diffuse Alveolar Hemorrhage: A Systematic Review.

Granulomatosis with polyangiitis (GPA) is a systemic disease that has variable clinical expression. GPA is the most common antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Diffuse alveolar hemorrhage (DAH) is one of the least common pulmonary manifestations in patients with GPA. DAH is clinically marked by hemoptysis, anemia, and diffuse alveolar infiltrates on imaging as well as hypoxemic respiratory failure. The diagnosis and treatment are challenging. Recommendations for ANCA-associated vasculitis, in general, are already established; however, there is a knowledge gap that addresses the association of GPA and DAH. The aim of this systematic review is to focus on the main clinical aspects and treatment of patients with GPA who present with DAH. Thorough research of available literature was performed, including studies published in the last 10 years, following the Preferred Items for Systematic Review and Meta-Analysis (PRISMA) 2020 recommendations. The following databases were included: PubMed, Medline, Embase, ClinicalTrials.com, Google Scholar, and Prospero. The search terms included: [granulomatosis] AND [polyangiitis] AND [diffuse alveolar hemorrhage] OR [diffuse pulmonary hemorrhage] NOT [microscopic polyangiitis] NOT [eosinophilic granulomatosis]. NOS was used to assess the internal validity of the study in four domains, including selection, ascertainment, causality, and reporting. Our initial search identified 8989 studies. After excluding duplicated data and using our predetermined inclusion and exclusion criteria, we were able to retrieve 18 studies. Twelve out of 18 (67%) studies were case reports. Five were retrospective cohorts and one controlled trial. The average age of patients with GPA with DAH was 49.55 ± 17.54 years (18 - 76). Male individuals had a slight predominance (59%) in comparison to female individuals (41%). The hemoglobin level at the time of presentation was 8.86 mg/dL ± 1.43. The majority of patients (61.5%) reported hemoptysis. Renal involvement was present in 66.7%. Patients who required mechanical ventilation represented 61.5%. Plasmapheresis was used in 71.4%. Mortality was 20%, and gender was not associated with mortality (p = 0.822). Hemoptysis was not associated with the need for mechanical ventilation (p = 0.928). Renal impairment was not a predictor of mechanical ventilation (p = 0.207). In summary, patients with GPA and DAH were severely ill, frequently had renal impairment upon admission, and frequently required mechanical ventilation. Steroids, rituximab, and cyclophosphamide are the first-line treatment, and plasmapheresis is still in use. Eventually, extracorporeal membrane oxygenation (ECMO) can be the salvage therapy. Randomized controlled clinical trials (RCTs) are needed to address the best therapeutic options for this population.

Large Fibroepithelial Stromal Polyp of the Breast Nipple.

Fibroepithelial stromal polyps (FEPs) are benign tumors of the integumentary system with mesodermal origin. They are commonly found over the skin. Rarely, they can be found in the nipple. We report a case in a 62-year-old female with a large FEP emerging from the left breast nipple. It started as a "mole" 10 years ago and slowly progressed in size. The patient did not complain of pain but did report occasional bloody discharge. She has no family history of breast cancer. On physical exam, a pedunculated large polyp, with rubbery consistency, emerging from the left nipple was noted. The lesion consisted of hyper-pigmentation with scattered ulcerations and cauliflower-like growth. Surgical excision was performed and histopathologic analysis showed extensive fibrovascular tissue with dense collagen fibers deposition consistent with FEP. Surgical treatment is curative with minimal skin deformity. In order to make the diagnosis and exclude malignancy, histopathology is mandatory.

Systemic cytomegalovirus masquerading as a colorectal mass in a patient with undiagnosed HIV/AIDS.

Introduction: Cytomegalovirus (CMV) infection is common among patients with human immunodeficiency virus (HIV) infection. Gastrointestinal (GI) involvement with tumor like lesion is a rare presentation. Our patient presented with rectal pain and findings concerning for malignancy. Subsequently our patient was diagnosed with acquired immunodeficiency syndrome (AIDS), CMV viremia and CMV proctitis. Case: A 37-year-old man who reported having sex with men presented with severe proctalgia and hematochezia. Imaging showed irregular rectal wall thickening concerning for malignancy. Sigmoidoscopy revealed a circumferential necrotic lesion suspicious for malignancy. Surprisingly, biopsy showed a cytopathic effect compatible with CMV infection. In addition to testing positive for CMV, patient was newly diagnosed with HIV/AIDS, hepatitis C, syphilis, and gonorrhea. CMV infection was treated with ganciclovir, which resulted in a significant response. Ganciclovir was later replaced with valganciclovir. Valganciclovir was continued and antiretroviral therapy (ART) was started as an outpatient and with resolution of symptoms. Discussion: CMV infection is one of the most common opportunistic infections among patients with HIV infection. Several cases of CMV colitis were reported among immunocompromised patients. Our patient's presenting symptoms and direct visualization of rectal lesion were not only deceptive but also unique. As what looked like a rectal malignancy was later diagnosed as tissue invasive CMV by biopsy. Invasive CMV infection should be managed with ganciclovir. Conclusion: GI CMV as the initial presentation of HIV is rare. Moreover, CMV proctitis can masquerade as a rectal cancer and clinicians should be aware of this rare presentation of CMV.

Tube Feeding-Related Bowel Ischemia Presenting As Extensive Intestinal Pneumatosis Complicated With Hepatic Portal Venous Gas.

Hepatic portal venous gas (HPVG) is a condition where air embolization from disrupted intestinal mucosa reaches the portal system. It is an uncommon finding and denotes severity. This report describes HPVG as a rare and lethal complication of enteral nutrition. The patient had a history of pancreatic adenocarcinoma (PADC) managed with Whipple's surgery, complicated with poor oral intake, requiring percutaneous jejunostomy. Subsequently, the patient presented with severe abdominal pain and distension. On imaging, he was found to have diffuse pneumatosis intestinalis (PI) and HPVG. The patient underwent exploratory laparotomy with intraoperative findings of bowel ischemia starting at the distal point of the enteral tube feeding. Despite aggressive intensive support, the patient died. The aim of this case description is to highlight a rare complication of enteral feeding with impressive imaging findings. Intensive care providers should consider this complication in patients with acute abdominal symptoms, who are under enteral feeding.

Severe Lactic Acidosis Due to Acute Intoxication by Emtricitabine/Tenofovir Alafenamide.

A 46-year-old female with a history of generalized anxiety disorder was admitted after intentional ingestion of an unknown amount of emtricitabine/tenofovir alafenamide (Descovy®) in a suicidal attempt. Patient was emergently intubated secondary to severe agitation and inability to protect airways. Patient developed severe lactic acidosis early in the admission, secondary as to a possible mitochondrial toxicity. Failed attempts to fluid resuscitation with Lactate Ringer®, eventually warranted to start the patient on norepinephrine infusion. Metabolic acidosis remained refractory to bicarbonate bolus and infusion. Hypothermia and hypoglycemia were corrected. Despite the initial approach, the patient remained acidotic, and the nephrology was consulted for emergent continuous renal replacement therapy (CRRT). After three days of intensive care unit stay and CRRT, the patient improved and was successfully decannulated. Her metabolic profile also showed remarkable improvement and the metabolic lactic acidosis resolved. The previous formulation of tenofovir with disoproxil fumarate is associated with severe lactic acidosis due to inhibition of mammalian mitochondrial DNA polymerase. Risk factors include liver cirrhosis, chronic kidney disease, hepatitis B and C coinfection, and metformin use. The new pharmaceutical formulation of tenofovir with alafenamide (TAF) has caused a significant decrease in the incidence of lactic acidosis. However, its real incidence and the usual plasma level to induce toxicity and mitochondrial dysfunction are unknown. The aim of this report is to highlight the risk of severe lactic acidosis with the use of TAF.

Effects of Eugenol and Dehydrodieugenol B from Nectandra leucantha against Lipopolysaccharide (LPS)-Induced Experimental Acute Lung Inflammation.

Acute lung injury (ALI) is an important public health problem. The present work investigated whether dehydrodieugenol B treatment, a compound isolated from Brazilian plant Nectandra leucantha (Lauraceae), modulates experimental ALI and compared the observed effects to eugenol. Effects of dehydrodieugenol B in vitro in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells were evaluated. The lung and systemic inflammatory profile, lung function, and possible mechanisms involved in BALB/C male mice (6-8 weeks) with ALI induced by LPS instillation (5 mg/kg) was assayed. Dehydrodieugenol B did not affect the cell viability and inhibited the increase in NO release and IL-1ß and IL-6 gene expression induced by LPS. In vivo, both compounds reduced lung edema, inflammatory cells, and the IL-6 and IL-1 ß levels in bronchoalveolar lavage fluid, as well as reduced inflammatory cell infiltration and those positive to iNOS, MMP-9, and TIMP-1, and reduced the collagen content and the 8-isoprostane expression in lung tissue. Eugenol and dehydrodieugenol B also inhibited the phosphorylation of Jc-Jun-NH2 terminal Kinase (JNK), a signaling protein involved in the MAPKinase pathway. There was no effect of these compounds in lung function. Therefore, eugenol and dehydrodieugenol B ameliorates several features of experimental ALI and could be considered as a pharmacological tool to ameliorate acute lung inflammation.

Oxidative phenotype induced by aerobic physical training prevents the obesity-linked insulin resistance without changes in gastrocnemius muscle ACE2-Angiotensin(1-7)-Mas axis.

BACKGROUND: We investigate the effect of aerobic physical training (APT) on muscle morphofunctional markers and Angiotensin Converting Enzyme 2/Angiotensin 1-7/Mas receptor (ACE2/Ang 1-7/Mas) axis in an obesity-linked insulin resistance (IR) animal model induced by cafeteria diet (CAF). METHODS: Male C57BL/6J mice were assigned into groups CHOW-SED (chow diet, sedentary; n = 10), CHOW-TR (chow diet, trained; n = 10), CAF-SED (n = 10) and CAF-TR (n = 10). APT consisted in running sessions of 60 min at 60% of maximal speed, 5 days per week for 8 weeks. RESULTS: Trained groups had lower body weight and adiposity compared with sedentary groups. CAF-TR improved the glucose and insulin tolerance tests compared with CAF-SED group (AUC = 28.896 ± 1589 vs. 35.200 ± 1076 mg dL-1 120 min-1; kITT = 4.1 ± 0.27 vs. 2.5 ± 0.28% min-1, respectively). CHOW-TR and CAF-TR groups increased exercise tolerance, running intensity at which VO2 max was reached, the expression of p-AMPK, p-ACC and PGC1-α proteins compared with CHOW-SED and CAF-SED. Mithocondrial protein expression of Mfn1, Mfn2 and Drp1 did not change. Lipid deposition reduced in CAF-TR compared with CAF-SED group (3.71 vs. 5.53%/area), but fiber typing, glycogen content, ACE2 activity, Ang 1-7 concentration and Mas receptor expression did not change. CONCLUSIONS: The APT prevents obesity-linked IR by modifying the skeletal muscle phenotype to one more oxidative independent of changes in the muscle ACE2/Ang 1-7/Mas axis.

Juvenile hormone affects age polyethism, ovarian status and cuticular hydrocarbon profile in workers of the wasp Polybia occidentalis.

Division of labor is one of the most striking features in the evolution of eusociality. Juvenile hormone (JH) mediates reproductive status and aggression among nestmates in primitively eusocial Hymenoptera (species without morphologically distinct castes). In highly social species it has apparently lost its gonadotropic role and primarily regulates the division of labor in the worker caste. Polybia occidentalis, a Neotropical swarm-founding wasp, is an ideal model to understand how JH levels mirror social context and reproductive opportunities because of the absence of a clear morphological caste dimorphism. In this study, we tested the hypothesis that JH influences division of labor, ovary activation and cuticular hydrocarbon profiles of workers. Our observations confirmed that a JH analog (methoprene) and an inhibitor of JH biosynthesis (precocene) affected the cuticular chemical profile associated with age polyethism. Also, methoprene and precocene-I treatment of females influenced ovarian activation differently (individuals treated with methoprene expressed more activated ovaries while precocene treatment did not have significant effect). These results suggest that different hormonal levels induce a differential expression of cuticular chemicals associated with workers' age polyethism, which may be essential for keeping the social cohesion among workers throughout their lives in the colony. Furthermore, JH is likely to play a gonadotropic role in P. occidentalis. JH has apparently undergone certain modifications in social Hymenoptera, presenting multifaceted functions in different species.

Pleural and Pericardial Infection Due to Cutibacterium acnes in a Splenectomized Patient: A Case Report of an Underreported Systemic Infection.

Infectious pericarditis does not always present with all the classic findings. Some of the traditional signs of fever, pleuritic chest pain, and frictional rub may be missing. This presents a diagnostic challenge, thus clinical suspicion is important. The most common cause of infectious pericarditis is viral. However, bacterial pericarditis may occur with severe complications such as constrictive pericarditis, pericardial effusion, cardiac tamponade, left ventricular pseudoaneurysm, and aortic mycotic aneurysm. The purpose of this presentation is to increase awareness of Cutibacterium acnes (C. acnes) as a cause of bacterial pericarditis. This case report highlights C. acnes as a prevalent cause of both pleural and pericardial infections. The diagnosis can be challenging, considering that this bacterium is difficult to isolate, slow growing, and causes indolent illness. Prolonged incubation time may be required. In addition to the more traditional causes of bacterial pericarditis, namely Staphylococcus and Streptococcus species, C acnes appears to play an important role. It should not be considered a contaminant as it may require further investigation.

Acute Disseminated Encephalomyelitis Related to a Cytomegalovirus Infection in an Immunocompetent Patient.

Cytomegalovirus (CMV) infection can cause acute disseminated encephalomyelitis (ADEM). However, it is rare in immunocompetent people. We describe a 17-year-old patient who was brought with flu-like symptoms. After one week, she experienced rapidly progressive weakness in all four extremities, followed by coma. The neurologic examination showed no response to verbal and pain stimuli. A Babinski sign was noted in both lower extremities, along with clonus and hyperreflexia in all four limbs. Brain magnetic resonance imaging (MRI) demonstrated extensive areas of hyperintense signal on fluid-attenuated inversion recovery (FLAIR) sequences in the white matter which was asymmetrically distributed in both hemispheres, as well as in the brainstem and cerebellar peduncles, compatible with acute demyelinating lesions. Cerebrospinal fluid (CSF) showed mild lymphocytic pleocytosis and normal glucose levels. Polymerase chain reaction to herpes simplex virus was negative. Serum immunoglobulin G (IgG) and immunoglobulin M (IgM) were positive for cytomegalovirus. The patient was treated with methylprednisolone pulse therapy for five days. Subsequently, the patient showed neurologic improvement with the recovery of consciousness and muscle strength. In terms of prognosis, in patients with ADEM, the sooner the diagnosis, the better the outcome. The cornerstone of treatment is immunosuppression with steroids. Some patients require intravenous immunoglobulin G (IVIG) or plasmapheresis, and in refractory cases, cyclophosphamide is used.

Dehydrodieugenol improved lung inflammation in an asthma model by inhibiting the STAT3/SOCS3 and MAPK pathways.

BACKGROUND: Eugenol, a common phenylpropanoid derivative found in different plant species, has well-described anti-inflammatory effects associated with the development of occupational hypersensitive asthma. Dehydrodieugenol, a dimeric eugenol derivative, exhibits anti-inflammatory and antioxidant activities and can be found in the Brazilian plant species Nectandra leucantha (Lauraceae). The biological effects of dehydrodieugenol on lung inflammation remain unclear. PURPOSE: This study aimed to investigate the effects of eugenol and dehydrodieugenol isolated from N. leucantha in an experimental model of asthma. METHODS: In the present work, the toxic effects of eugenol and dehydrodieugenol on RAW 264.7 cells and their oxidant and inflammatory effects before lipopolysaccharide (LPS) exposure were tested. Then, male BALB/c mice were sensitized with ovalbumin through a 29-day protocol and treated with vehicle, eugenol, dehydrodieugenol or dexamethasone for eight days beginning on the 22nd day until the end of the protocol. Lung function; the inflammatory profile; and the protein expression of ERK1/2, JNK, p38, VAChT, STAT3, and SOCS3 in the lung were evaluated by immunoblotting. RESULTS: Eugenol and dehydrodieugenol were nontoxic to cells. Both compounds inhibited NO release and the gene expression of IL-1ß and IL-6 in LPS-stimulated RAW 264.7 cells. In OVA-sensitized animals, dehydrodieugenol reduced lung inflammatory cell numbers and the lung concentrations of IL-4, IL-13, IL-17, and IL-10. These anti-inflammatory effects were associated with inhibition of the JNK, p38 and ERK1/2, VAChT and STAT3/SOCS3 pathways. Moreover, treatment with dehydrodieugenol effectively attenuated airway hyperresponsiveness. CONCLUSION: The obtained data demonstrate, for the first time, that dehydrodieugenol was more effective than eugenol in counteracting allergic airway inflammation in mice, especially its inhibition of the JNK, p38 and ERK1/2, components of MAPK pathway. Therefore, dehydrodieugenol can be considered a prototype for the development of new and effective agents for the treatment of asthmatic patients.

Inhibition of MAPK and STAT3-SOCS3 by Sakuranetin Attenuated Chronic Allergic Airway Inflammation in Mice.

Asthma allergic disease is caused by airway chronic inflammation. Some intracellular signaling pathways, such as MAPK and STAT3-SOCS3, are involved in the control of airway inflammation in asthma. The flavonoid sakuranetin demonstrated an anti-inflammatory effect in different asthma models. Our aim was to clarify how sakuranetin treatment affects MAPK and STAT3-SOCS3 pathways in a murine experimental asthma model. Mice were submitted to an asthma ovalbumin-induction protocol and were treated with vehicle, sakuranetin, or dexamethasone. We assayed the inflammatory profile, mucus production, and serum antibody, STAT3-SOCS3, and MAPK levels in the lungs. Morphological alterations were also evaluated in the liver. LPS-stimulated RAW 264.7 cells were used to evaluate the effects of sakuranetin on nitric oxide (NO) and cytokine production. In vivo, sakuranetin treatment reduced serum IgE levels, lung inflammation (eosinophils, neutrophils, and Th2/Th17 cytokines), and respiratory epithelial mucus production in ovalbumin-sensitized animals. Considering possible mechanisms, sakuranetin inhibits the activation of ERK1/2, JNK, p38, and STAT3 in the lungs. No alterations were found in the liver for treated animals. Sakuranetin did not modify in vitro cell viability in RAW 264.7 and reduced NO release and gene expression of IL-1ß and IL-6 induced by LPS in these cells. In conclusion, our data showed that the inhibitory effects of sakuranetin on eosinophilic lung inflammation can be due to the inhibition of Th2 and Th17 cytokines and the inhibition of MAPK and STAT3 pathways, reinforcing the idea that sakuranetin can be considered a relevant candidate for the treatment of inflammatory allergic airway disease.

Macedo procedure: A continent catheterizable ileum-based reservoir. Step-by-step video.

This video provides a case report of a 16-year-old male patient who underwent bladder enlargement with a catheterized conduit under Macedo's technique. This technique involves the use of a segment of the distal ileum with a flap that is used for confection of the conduit. Key points include: 1) skin incision planning; 2) bladder release to allow a tension-free anastomosis; 3) reservoir and a conduit creation with a distal ileum; and 4) creation of a continence mechanism.

BODY IMAGE AMONG MEN WHO PRACTICE BODY BUILDING: COMPARISON BY AGE, ECONOMIC STATUS, AND CITY SIZE.

Identifying the factors that influence the body image of body builders is important for understanding this construct. The aim of this study was to analyze the association between body image and age, socioeconomic status, and place of residence of body builders from two cities in Brazil. A cross-sectional study of 301 body builders with an average age of 25.2 yr. (SD = 3.5) was carried out. The Muscle Silhouette Measure scale was used, in which the discrepancy between current and desired silhouette was examined. Older body builders showed greater discrepancy between current and desired silhouette, reflecting their desire for a more muscular body.

Using heart rate to prescribe physical exercise during head-out water immersion.

The purpose of this study was to compare and correlate the effect of age group, sex, depth of water immersion, and the heart rate (HR) assessed out of the water on the HR behavior in individuals subjected to head-out water immersion. A total of 395 healthy individuals of both sexes, aged between 07 and 75 years, underwent vertical head-out water immersion. Heart rate was assessed out of the water in the supine and orthostatic (OHR) positions and at immersion depths corresponding to the ankle, knee, hip, umbilicus, xiphoid process, acromion, neck, and also the neck with the arms out of the water. The formula (ΔHR = OHR - HR immersion depth) was used to calculate the reduction in HR at each immersion depth. No age-based or sex-based differences in HR were found. The greater the depth of the water, the greater was the decrease in HR (p < 0.05); however, no differences were found between the HR values obtained below the depth corresponding to the umbilicus. Similarly, there was a significant relationship between OHR and ΔHR measured at levels below the depth corresponding to the umbilicus (e.g., xiphoid process level: r = 0.62; p < 0.05). Therefore, this study suggests to appropriately prescribe the intensity of water-based exercise intensity performed during vertical immersion: OHR should be measured before the individual entering the aquatic environment; ΔHR should be measured according to the depth at which exercise is to be performed, and we suggest an adaptation to Karvonen's HRmax prediction formula (predicted HRmax: 220 - age - ΔHR) to prescribe and control the intensity of the exercise performed during vertical immersion.