Kidney Histopathology of Patients with Hepatitis C Infection and Diabetes Mellitus before and after Availability of Direct-Acting Antiviral Therapy.

Introduction: Type 2 diabetes mellitus (DM) and diabetic kidney disease are increasing. Hepatitis C infection (HCV) occurs in 1% of the world population and can induce several kidney diseases. DM prevalence is increased in individuals with HCV; however, kidney diseases in those with both DM and HCV have not been assessed. Direct-acting antiviral agents (DAAs) became available for HCV treatment in 2014; it is unknown if DAAs altered the spectrum of kidney disease in patients with DM and HCV. Methods: Case review identifying patients with kidney biopsy and clinical history of DM and HCV between 2009-2013 (pre-DAA) and 2016-2020 (post-DAA), excluding kidney transplant, hepatitis B, HIV, and inadequate biopsy, identified 245 biopsies. Biopsies were evaluated for diabetic glomerulosclerosis (DGS) class, global and focal segmental glomerulosclerosis (FSGS), other glomerular diseases, interstitial fibrosis/tubular atrophy (IFTA), interstitial nephritis, acute tubular injury and degree of arterial and arteriolar sclerosis. Kidney disease differences in pre-DAA versus post-DAA eras and in mild versus severe DGS were assessed by χ2 and Fisher's exact tests. Results: The most common non-DGS lesions were non-collapsing FSGS (41%), HCV-related IgM dominant immune complex glomerulonephritis (IgM-ICGN, 18%), IgA nephropathy (9%), and membranoproliferative glomerulonephritis (MPGN, 7%). Collapsing FSGS was more common pre-DAA versus post-DAA (8% vs. 1%, p = 0.03). Biopsies from patients with HCV and DM were reduced in post-DAA (0.7%) versus pre-DAA (1.3%) (p < 0.0001). Post-DAA there were less MPGN (2% vs. 10%, p = 0.02) and more advanced DGS (85% vs. 61%, p = 0.0002), non-collapsing FSGS (57% vs. 31%, p < 0.0001), IFTA (2.0 vs. 1.6, p = 0.0002), and vascular sclerosis (2.1 vs. 1.6, p < 0.0001). Conclusion: Post-DAA there were reduced biopsies and MPGN, with more severe DGS class, non-collapsing FSGS, IFTA, and chronic vascular changes. This suggests a modulating effect of DAAs on HCV-related kidney pathology with DM and chronic changes driving indications for kidney biopsy.

Characteristics of Renal Intravascular Large B-cell Lymphoma.

Introduction: Renal intravascular large B-cell lymphoma (IVLBCL) is a rare, aggressive B-cell lymphoma with neoplastic cells occupying the vascular lumina with only 53 patients reported to date. Here, we present the largest case series to characterize this rare disease. Methods: We performed a multi-institutional, retrospective review of kidney biopsies and autopsies with a diagnosis of kidney IVLBCL and report our findings. Results: We identified 20 patients with an average age of 65.7 ± 7.8 years (55% males) with IVLBCL on kidney biopsy. The most common clinical presentation was fever and anemia. Acute kidney injury (AKI) was noted in 70% to 90%, proteinuria in 70% to 84.1%, hematuria in 45%, and nephrotic-range proteinuria in 10% to 26.1% of cases. The median (interquartile range) of serum creatinine was 1.75 (1.14, 3.3) mg/dl. Neoplastic lymphoid cells were present in glomeruli, peritubular capillaries, and arteries or veins. Of the patients, 44.3% showed extrarenal infiltration into bone marrow, liver, spleen, central vervous system, lung and skin. Neoplastic cells express CD20, CD79a, PAX-5, and MUM1+, and were CD10-negative. Available follow-up data showed a median survival of 21 months after diagnosis. Extrarenal involvement is a significant and independent predictor of mortality with a hazard ratio of 4.975 (95% confidence interval:1.38, 17.88) after controlling for age and gender. Serum creatinine, age, sex, and infiltration of intrarenal arteries or veins did not affect survival. Conclusion: Kidney IVLBCL is a rare disease that is unexpectedly diagnosed by kidney biopsy, presenting with fever, anemia, mild AKI, and proteinuria. Median survival is 21 months and extrarenal involvement is associated with worse outcome.

Adalimumab-Induced Lupus Nephritis: Case Report and Review of the Literature.

Tumor necrosis factor-alpha inhibitors are known causative agents of systemic lupus erythemato- sus but have rarely been implicated in lupus nephritis. A patient with Crohn's disease on long-term adalimumab treatment presented with new-onset Raynaud's phenomenon and was found to have hematuria and proteinuria. Elevated antinuclear, anti-dsDNA, and MPO antibodies were found. A renal biopsy confirmed the diagnosis of lupus nephritis. Adalimumab was discontinued ensuing improvement in urine studies and resolution of dsDNA and MPO antibodies. Adalimumab can induce systemic lupus erythematosus and lupus nephritis.

The Prevalence of Mesangial Electron-Dense Deposits in PLA2R-Positive Membranous Nephropathy.

INTRODUCTION: Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults and can be primary or secondary. The antigenic target of antibodies in 70% of primary cases is phospholipase A2 receptor (PLA2R). The presence or absence of mesangial electron-dense deposits has been used to distinguish between primary and secondary MN. Mesangial deposits suggest MN due to lupus, infection, or other causes, though they are reported to occur in approximately 10% of primary MN. Staining for PLA2R is now frequently used for confirming a diagnosis of primary MN. If mesangial deposits predict a secondary cause, they should be more frequent in PLA2R-negative biopsies. METHODS: A review of institutional kidney biopsies between March 2017 and June 2020 identified all cases of MN. Cases with a diagnosis of lupus or near "full-house" staining by immunofluorescence microscopy (IF) were excluded. Light microscopy, IF, and electron microscopy (EM) were performed. PLA2R staining was performed by IF. EM for all cases was reviewed and electron-dense deposit location, distribution, and size were determined. RESULTS: Ninety-three cases of MN were identified, of which 86 had both PLA2R staining and EM performed. Of these, 51 cases (59%) were positive for PLA2R and 35 (41%) were negative. Mesangial electron-dense deposits were present in 22 (25.6%) of the 86 cases, including 27.5% (14/51) of PLA2R-positive cases and 22.8% (8/35) of PLA2R-negative cases. No difference was seen in size or distribution of deposits, or other features considered suggestive of secondary MN. CONCLUSION: PLA2R-negative cases were not more likely to have mesangial deposits than PLA2R-positive cases. Mesangial deposits should not be used as an indicator of secondary MN.

Podocytopathy in Obesity: Challenges of Living Large.

Renal injury resulting from obesity is a growing concern caused by the global obesity epidemic. We discuss the glomerular structure, obesity-related glomerular changes, and diagnostic pathologic criteria for obesity-related glomerulopathy. The three main hypothesized mechanisms of podocyte injury are mechanical stress on the podocytes, metabolic derangement, and genetic/molecular factors. Weight loss, renin-angiotensin-aldosterone system inhibitors, and improved insulin resistance may slow the progression. A more comprehensive understanding of obesity-related glomerulopathy will help in developing more effective therapies.

An Organ System-Based Approach to Differential Diagnosis of Amyloid Type in Surgical Pathology.

CONTEXT.­: Amyloidosis is an uncommon but important entity. A protein-based classification of amyloidosis defines the underlying disease process, directing clinical management and providing prognostic information. However, in routine surgical pathology there often is no attempt to classify amyloid other than staining to determine light chain-associated amyloidosis. Systemic and localized amyloidosis vary with respect to frequency of organ involvement by different amyloid types, and most amyloid proteins have commercial antibodies available for identification. OBJECTIVE.­: To provide a guide for the likelihood of amyloid type by organ system. DATA SOURCES.­: Literature review based on PubMed searches containing the word amyloid, specifically addressing the prevalence and significance of amyloid proteins in each organ system other than the brain, and the authors' practice experience. CONCLUSIONS.­: In patients with amyloidosis, determination of the responsible protein is critical for appropriate patient care. In large subspecialty practices and reference laboratories with experience in using and analyzing relevant immunohistochemistry, most amyloid proteins can be identified with an organ-specific algorithm. Referring to an organ-based algorithm may be helpful in providing clinicians with a more specific differential diagnosis regarding amyloid type to help guide clinical evaluation and treatment. When the protein cannot be characterized, mass spectrometry can be performed to definitively classify the amyloid type.

Intravascular B-cell lymphoma: case report of a rare cause of pulmonary arterial hypertension.

BACKGROUND: Intravascular large B-cell lymphoma (IVLBCL) is a rare disease characterized by proliferation of malignant lymphoid cells within the small vessels of various organs resulting in diffuse thrombosis. It most commonly affects the central nervous system and the skin, but if it involves the pulmonary arteries it can cause acute severe pulmonary hypertension (PH) and right heart failure. Early diagnosis is essential as the clinical course is extremely aggressive. In this report, we present a case of rapidly progressive PH and subsequent right ventricular (RV) failure secondary to IVLBCL. We review the important differential diagnoses and diagnostic evaluation needed to make a correct and early diagnosis. CASE SUMMARY: A 53-year-old, previously healthy man developed 2 months of progressive shortness of breath. After being treated for presumptive pneumonia, he was admitted with hypoxic respiratory failure, altered mental status, and severe PH. He developed RV failure and subsequent liver failure. He was ruled out for pulmonary embolism. Despite aggressive management with inhaled nitric oxide and epoprostenol, inotropes, and continuous renal replacement therapy, the patient passed away. Post-mortem examination revealed the presence of IVLBCL with extensive involvement notable of the brain, heart, lungs, and pulmonary arteries. DISCUSSION: The acute development of severe PH and RV failure in the absence of pulmonary emboli is uncommon and represents a challenging diagnostic and management clinical scenario. When accompanied by altered mental status, constitutional symptoms and an elevated lactate dehydrogenase, clinicians should have a high index of suspicion for intravascular lymphoma, as early diagnosis is critical to maintain a reasonable chance of survival.

Molecular characterization of metaplastic breast carcinoma via next-generation sequencing.

Metaplastic breast carcinoma (MBC) is a rare subtype of breast cancer with variable morphology. MBC is more often triple negative (ER-, PR-, HER2-) and is associated with poorer clinical outcome when compared with infiltrating ductal carcinoma. The purpose of our study is to identify molecular alterations in MBC using next-generation sequencing (NGS), which may aid chemotherapy selection and use of targeted therapy. A cohort of 18 patients with MBC yielded adequate DNA from microdissected formalin-fixed and paraffin-embedded tumor blocks. NGS was performed using the Ion AmpliSeq cancer hotspot mutation panel version 2 kit, which targets hotspot regions in 50 genes. Immunohistochemical stains for androgen receptor (AR), and programmed cell death ligand-1 were performed. A total of 23 genetic alterations were identified in 15 (83.3%) of 18 patients. Eleven genetic alterations in the PI3K signaling pathway were identified in 9 (50.0%) of 18 patients, including 7 PIK3CA mutations (38.9%), 3 PTEN genetic alterations (16.7%), and 1 AKT1 mutation (5.6%). Ten (55.6%) of 18 patients each harbored 1 TP53 genetic alteration. Additional genetic alterations identified were 1 HRAS mutation and 1 ATM mutation. AR immunoreactivity was identified in 2 (11.1%) of 18 patients. Programmed cell death ligand-1 was negative in all patients. NGS analysis demonstrated that PI3K pathway-related genetic alterations were detected in a high percentage of MBCs, suggesting that targeting the PI3K/mTOR pathway may be promising in patients with MBC. In addition, patients with AR expressing MBC may benefit from androgen antagonist treatment.

Eficacia y seguridad de la instilación precoz de estreptoquinasa intrapleural en el tratamiento del empiema paraneumónico complicado en niños / Efficacy and safety of early intrapleural instillation of streptokinase in the treatment of complicated parapneumonic empyema in children

En enero de 2005, en el Hospital Pediátrico del Centro Hospitalario Pereira Rossell se implementó un protocolo de instilación de estreptoquinasa (STK) intrapleural como alternativa al tratamiento quirúrgico del empiema complicado. La STK intrapleural administrada en los primeros ocho d¡as de colocado el drenaje disminuy la duracion del drenaje de tórax, la necesidad de toracotom¡a y la estad¡a hospitalaria. Objetivo.: describir los resultados de la instilación intrapleural precoz de STK en niños hospitalizados con empiema paraneumónico complicado, y compararlos con los resultados obtenidos tras la instilación en los primeros ocho d¡as de colocado el drenaje de tórax. Material y método: se incluyeron los niños con empiema paraneumónico complicado hospitalizados entre el 1º de abril de 2005 y el 30 de set. de 2007. Se dividieron en dos cohortes. Histórica: niños hospitalizados entre el 1º de abril de 2005 y el 1º de agosto de 2006, en los que el diagnóstico de empiema complicado se hizo según criterios cl¡nicos y ecográficos, que recibieron STK intrapleural en los primeros ocho d¡as luego de colocado el drenaje de tórax. Prospectiva: niños hospitalizados entre el 1º de marzo y el 30 de setiembre de 2007 diagnosticados y tratados según el nuevo protocolo. Se comparó la evolución mediante las siguientes variables: duración del drenaje de tórax, complicaciones, necesidad de toracotom¡a, estad¡a hospitalaria y muerte. Resultados: ambos grupos fueron comparables. La duración de la estad¡a hospitalaria y deldrenaje de tórax fueron menores en los niños tratados con STK intrapleural en forma precoz (p<0,05). Requirieron toracotom¡a dos niños, uno en cada cohorte. El número y tipo de complicaciones fue similar en ambos grupos. Ninguno de los pacientes incluidos en el estudio falleció. Conclusiones: la instilación intrapleural precoz de STK constituye una alternativa terapéutica para el tratamiento de niños con empiema paraneumónico complicado.

In January 2005, a protocol was implemented at the Pereira Rossell Hopital Centre, for the administration of intrapleural streptokinase (STK) as an alternative to surgical treatment of complicated empyema. Intrapleural STK, when administered in the first eight days subsequent to the placing of the drainage diminished the duration of thoracic drainage, the need for thoracotomy and a prolonged stay in hospital. Objective: to describe results of early intrapleural instillation of streptokinase in children hospitalized with complicated parapneumonic empyema, and to compare them to the results obtained after instillation during the first eight days subsequent to the placement of thoracic drainage. Method: children with complicated parapneumonic empyema that were hospitalized from April 1, 2005 through September 30, 2007 were included in the study. They were divided into two cohorts. Historical: children hospitalized from April 1, 2005 and August 1, 2006, when diagnosis of complicated empyema was made according to clinical and ecographic criteria, who received intrapleural STK during the first eight days subsequent to the placement of thoracic drainage. Prospective: children hospitalized from March 1, 2007 and September 30, 2007, diagnosed and treated according to the new protocol. Evolution was compared through the following variables: duration of thoracic drainage, complications, need for thoracotomy, duration of hospital stay and death. Results: both groups were comparable. Duration of hospital stay and thoracic drainage were lower in children treated with early intrapleural STK (p<0,05). Two children required thoracotomy, one in each cohort group. The number and type of complications was similar in both groups. None of the patients included in the study died. Conclusions: early intrapleural instillation of STK constitutes a therapeutic alternative in the treatment of children with complicated parapneumonic empyema.

Em janeiro de 2005, no Hospital Pediátrico do Centro Hospitalar Pereira Rossell foi implementado um protocolo de instilação de estreptoquinase (STK) intrapleural como alternativa ao tratamento cirúrgico do empiema complicado. A STK intrapleural administrada nos primeiros oito dias após a colocação do dreno reduziu a duração da drenagem de tórax, a necessidade de toracotomia e a permanência no hospital. Objetivo: descrever os resultados da instilação intrapleural precoce de STK em crianças hospitalizadas com empiema parapneumônico complicado, e fazer uma comparação com os resultados obtidos após a instilação nos primeiros oito dias após o começo da drenagem de tórax. Material e método: foram inclu¡das crianças com empiema parapneumônico complicado internadas no per¡odo 1º de abril de 2005 - 30 de setembro de 2007. Foram divididas em duas coortes. Histórico: crianças internadas no per¡odo 1º de abril de 2005 - 1º de agosto de 2006, com diagnóstico de empiema complicado feito por critérios clínicos e ecográficos, que receberam STK intrapleural nos primeiros oito dias após a colocação da drenagem de tórax. Prospectiva: crianças internadas no per¡odo 1º de março - 30 de setembro de 2007 diagnosticadas e tratadas de acordo como o novo protocolo. A comparação da evolução foi feita empregando as seguintes variáveis: duração da drenagem de tórax, complicações, necessidade de toracotomia, permanência no hospital e morte. Resultados: os resultados de ambos grupos eram comparáveis. A duração da internação e da drenagem de tórax foi menor nas crianças tratadas com STK intrapleural precoce (p<0,05). Em duas crianças foi necessário realizar toracotomia, uma em cada coorte. O número e tipo de complicações foi similar em ambos grupos. Nenhum paciente faleceu. Conclusões: a instilação intrapleural precoce de STK‚ uma alternativa terapêutica para o tratamento de crianças com empiema parapneumônico complicado.

Implantes protésicos testiculares en la infancia y la adolescencia: ¿son importantes? / Testicular prothesis implants: In childhood and adolescence: are they important?

Comunicamos la experiencia de nuestro equipo interdisciplinario en la asistencia de 85 pacientes con implantesprotésicos testiculares (IPT) y sus familias, desde diciembre de 1985 a diciembre de 2005. Se realiza un análisisprincipalmente dinámico-cualitativo de los procesos. Nuestro propósito es demostrar la importancia de la tarea de prevención de los diferentes impactos de la enfermedad. La edad media de nuestra población fue de 6,3 años, con una mediana de 5,8 años, el rango etario va de 1,7 años a los 14 años, realizándose un seguimiento desde los 0 años a 20 años con un promedio de 7,6 años y una mediana de 7 años. Se describen estrategias del equipo que desarrollan una asistencia temprana e integral (multidisciplinaria) en eltratamiento con IPT. Éstas posibilitan mitigar en el desarrollo del paciente la presencia de dificultades, principalmente a nivel del esquema corporal, la autoestima, el desarrollo de la sexualidad y la inserción social. Deesta manera se promueve una mejor calidad de vida para el niño y su grupo familiar. La evaluación de la experiencia realizada ha sido satisfactoria y se observó en los pacientes, en general, un alto nivel de satisfacción en relación al tratamiento, por lo que recomendamos el empleo de los IPT.

An interdisciplinary team-work experience in the assistance of 85 patients with silicone testicular prosthesis (STP) as well as the families’ guidance from December 1985 until December 2005 is presented. Our purpose is to demonstrate the importance of prevention in the different aspects of this pathology. The age average was 6,3 years old, with a media of 5,8. The ages ranged between 1,7 to 14 years old. Frequent checkups were carried out since newborns until the age of 20, with an average age of 7,6 years and a media of 7. The team’s strategies used for an early assistance are described. They help prevent the difficulties these patients suffer specially related to their physical appearance, self-respect, sexual behaviour and social acceptance. As aresult a good life quality of the whole family group was successfully promoted.The working experience was satisfactory and most of the patients showed a high approval degree in regards to the treatment. Therefore we strongly recommend the use of the STP.

La relación técnico-paciente: rol de la información / Physician-patient relation: role of information

En los últimos cincuenta años se viene registrando la preocupación progresiva de médicos y psicólogos, sobre la repercusión a nivel afectivo del acto quirúrgico en el paciente y su familia. Al respecto, se han realizado diferentes trabajos aportando determinadas articulaciones teóricas y conclusiones. Desde este marco se efectúa esta comunicación. Objetivo: Comunicar una experiencia laboral conjunta, que busca ser punto de partida de una reflexión. Se limita en su contenido a ser un trabajo de tipo descriptivo, referente a un servicio de Cirugía Pediátrica. Se pretende hacer un análisis dinámico del proceso, mostrando la relación técnico-paciente a través de la inclusión del psicólogo y el rol fundamental de la información en dicho vínculo. Metodología: A punto de partida de la observación durante tres meses del funcionamiento de un servicio de cirugía en lo referente a la relación técnico-paciente, se desarrolla una metodología basada fundamentalmente en el rol de la información. La tarea que así se funda, se realiza sostenida en el trabajo conjunto de médico, familia y psicólogo. Se registraron las señales-testimonios de los grupos estudiados previos a la intervención y posteriormente, dando cuenta estos últimos de la efectividad de la tarea