Comorbid Ankylosing Spondylitis and Systemic Lupus Erythematosus: A Therapeutic Challenge.

Ankylosing spondylitis (AS) and systemic lupus erythematosus (SLE) are common rheumatologic ailments that cause multiorgan system disease. The incidence of lupus and AS in the same patient is rare and has seldom been described in the literature. Comorbid lupus and AS provide interesting diagnostic and therapeutic challenges. Here, we present a case of comorbid lupus and AS, discuss the diagnostic challenges in diagnosing these conditions, and put forth possible therapeutic interventions that may benefit similar patients.

Myelodysplastic Neoplasms (MDS): The Current and Future Treatment Landscape.

Myelodysplastic neoplasms (MDS) are a heterogenous clonal disorder of hemopoietic stem cells characterized by cytomorphologic dysplasia, ineffective hematopoiesis, peripheral cytopenias and risk of progression to acute myeloid leukemia (AML). Our understanding of this disease has continued to evolve over the last century. More recently, prognostication and treatment have been determined by cytogenetic and molecular data. Specific genetic abnormalities, such as deletion of the long arm of chromosome 5 (del(5q)), TP53 inactivation and SF3B1 mutation, are increasingly associated with disease phenotype and outcome, as reflected in the recently updated fifth edition of the World Health Organization Classification of Hematolymphoid Tumors (WHO5) and the International Consensus Classification 2022 (ICC 2022) classification systems. Treatment of lower-risk MDS is primarily symptom directed to ameliorate cytopenias. Higher-risk disease warrants disease-directed therapy at diagnosis; however, the only possible cure is an allogenic bone marrow transplant. Novel treatments aimed at rational molecular and cellular pathway targets have yielded a number of candidate drugs over recent years; however few new approvals have been granted. With ongoing research, we hope to increasingly offer our MDS patients tailored therapeutic approaches, ultimately decreasing morbidity and mortality.

Ductal Adenocarcinoma of the Prostate with Novel Genetic Alterations Characterized by Next-Generation Sequencing.

Ductal adenocarcinoma of the prostate (DAP) is an uncommon variant of prostate cancer associated with aggressive disease and poor outcome. It presents most frequently as a mixed tumor combined with acinar adenocarcinoma. Although the histopathological features of DAP are well known, its genomic characteristics are still evolving, prompting the suggestion that all DAP would benefit from molecular analysis with the purpose of improving tumor recognition, genetic classification, and, ultimately, personalized therapy. Herein, we report a case of DAP with novel genetic alterations (BCOR P1153S, ERG M219I, KDR A750E, POLE S1896P, and RAD21 T461del).

Hemodialysis Wastewater Treatment via Electrocoagulation and Electro-Oxidation: Modular Pilot-Level Modeling and Simulation.

Hemodialysis treatment in specialized clinics within the same hospital significantly impacts environmental water health due to contaminated wastewater. The issues observed included changes in electrical conductivity, the presence of dangerous bacterial loads, toxicity from heavy metals, total cyanide content, and helminth parasite eggs. The level of damage is dependent on the patient's health under treatment. This research will use a modular system that employs electrocoagulation and electro-oxidation processes at the laboratory and pilot levels to treat hemodialysis wastewater using synthetically prepared and real samples extracted from local clinics. The results showed that these hybrid systems improved various physicochemical parameters. Specifically, decreases in electrical conductivity of 49 %, total suspended solids of 27-100 %, chemical oxygen demand of 49 %, biochemical oxygen demand of 49 %, and cation and anion loading were observed at 96-100 % and pH 8.13 UpH in accordance with the established standards. With these results and the experimental conditions used, the proposed treatment system was modeled using the GPS-X program, and it was concluded that the modular system used and the electrocoagulation/electro-oxidation/activated carbon configuration is suitable for treating wastewater from hemodialysis and that scaling up this process to facilities that have dialysate machines more advanced than those considered in this work is possible.

IgA plasma cell myeloma presenting as cold agglutinin-induced haemolytic transfusion reaction.

Cold agglutinins produced in the setting of B cell neoplasms, such as lymphoplasmacytic lymphoma and plasma cell myeloma, can mediate autoimmune haemolytic anemia. Transfusion of these patients can exacerbate cold agglutinin-mediated haemolysis. Moreover, the workup for these reactions represents a diagnostic challenge due in part to false negative direct antiglobulin tests (DATs). Here, we report an anaemic patient who after a red blood cell (RBC) transfusion performed without blood warming, experienced a DAT-negative haemolytic transfusion reaction, and was later diagnosed with IgA-multiple myeloma, which showed an uncommon granular pattern by CD138 immunohistochemistry. Extensive workup excluded other diagnostic possibilities, including the presence of Donath-Landsteiner antibodies and cryoglobulins. Successful treatment with CyBorD (cyclophosphamide, bortezomib and dexamethasone) achieved complete remission, and additional RBC transfusions using warmers were completed uneventfully.

[Basic health indicators in the NutrIMSS program: a retrospective study]. / Indicadores básicos de salud en el programa NutrIMSS: estudio retrospectivo.

Background: The NutrIMSS program is granted to populations with chronic conditions to improve basic health indicators and its effectiveness in this population is unknown. Objective: To analyze the change in the basic health indicators of patients who attended the NutrIMSS Program, at the UMF No. 2 of the IMSS in Mexico City, during the period 2018 to 2019. Material and methods: From 105 files of IMSS beneficiaries, a retrospective cohort study was carried out considering two measurements, before and after the NutrIMSS program. To evaluate the average change over time of health indicators, GEE models (Generalized Estimation Equations) and multiple linear regression models were used. Statistical analysis was used using the statistical program StataCorp 2015. Results: Patients who attended the Program showed changes between the beginning and end of the period with an average of three months of follow-up. They presented a decrease in the following health indicators: body weight of 1 kg, body mass index: 0.8 kg/m2, glucose of 13 mg/dL, triglycerides of 57 mg/dL and cholesterol of 17 mg/dL (p < 0.005 in all cases). There was no difference in the level of blood pressure. Conclusions: The NutrIMSS program influenced the improvement of the health indicators of the population of the program and is an ally to improve the health of the IMSS beneficiary population.

Introducción: el programa NutrIMSS se otorga a población con padecimientos crónicos para mejorar los indicadores básicos de salud; sin embargo, se desconoce su efectividad en esta población. Objetivo: analizar el cambio en los indicadores básicos de salud de pacientes que acudieron al programa NutrIMSS, en la UMF No. 2 del Instituto Mexicano del Seguro Social (IMSS) en la Ciudad de México, durante el periodo 2018 a 2019. Material y métodos: a partir de 105 expedientes de derechohabientes del IMSS se realizó un estudio de cohorte retrospectiva, considerando dos mediciones, antes y después del programa NutrIMSS. Para evaluar el cambio promedio en el tiempo de los indicadores de salud se utilizaron modelos GEE (Ecuaciones de Estimación Generalizadas) y modelos de regresión lineal múltiple. Para el análisis estadístico se utilizó el programa estadístico StataCorp 2015. Resultados: los pacientes que acudieron a NutrIMSS mostraron cambios entre el inicio y el fin del periodo, con un promedio de seguimiento de tres meses. Presentaron una disminución en los siguientes indicadores de salud: peso corporal de 1 kg, índice de masa corporal: 0.8 kg/m2, glucosa de 13 mg/dL, triglicéridos de 57 mg/dL y colesterol de 17 mg/dL (p < 0.005, en todos los casos). No se presentó diferencia en el nivel de la tensión arterial. Conclusiones: el programa NutrIMSS influyó para mejorar los indicadores de salud de la población del programa y es un aliado en la mejora de la salud de la población derechohabiente del IMSS.

[Academic satisfaction in residents of the north zone, Mexico City]. / Satisfacción académica en residentes de la zona norte, ciudad de México.

Background: Resident academic satisfaction has been linked to academic performance and quality of care. Objective: To analyze the perception of academic satisfaction in medical residents of the North Decentralized Administrative Operation Body 2 of the Instituto Mexicano del Seguro Social (IMSS), north of Mexico City. Material and methods: Cross-sectional analytical study. A total of 346 resident physicians of different specialties and academic degrees were found, enrolled in the residence halls in the northern zone of the IMSS, Mexico City from January to February 2022. The dependent variable was the level of academic satisfaction. Descriptive and inferential statistics and p ≤ 0.05 were produced for statistical significance. Results: The level of high satisfaction was 80.6% and the level of poor or low satisfaction was 1.7%. The dimension most affected in the negative bases was that of "Perception of teaching" in which 13% of the doctors surveyed refer to the need for some retraining of teachers. The best qualified dimension was "Perception of the role of autonomies" where 35.3% have an excellent perception of their personal work. The highest degree of satisfaction decreased during the second year. Conclusion: There is a high degree of satisfaction among resident doctors, however it is necessary to work to improve satisfaction in the remaining 20%.

Introducción: la satisfacción académica del residente se ha vinculado con el rendimiento académico y la calidad en la atención. Objetivo: analizar la percepción de la satisfacción académica en médicos residentes del Órgano de Operación Administrativa Desconcentrada 2 Norte del Instituto Mexicano del Seguro Social (IMSS), zona norte de la Ciudad de México. Material y métodos: estudio transversal analítico. Se encuestó a 346 médicos residentes de diferentes especialidades y grados académicos, inscritos en las sedes de residencia de la zona norte del IMSS, en la Ciudad de México de enero a febrero del 2022. La variable dependiente fue el nivel de satisfacción académica. Se utilizó estadística descriptiva, inferencial y p ≤ 0.05 para la significancia estadística. Resultados: el nivel de satisfacción alta fue del 80.6% y el nivel de satisfacción pobre o bajo fue del 1.7%. La dimensión más afectada en las puntuaciones negativas fue la de Percepción de la enseñanza, en la que el 13% de los médicos encuestados refieren la necesidad de algún reentrenamiento en los profesores. La dimensión mejor calificada fue la de Percepción del rol de autonomías, donde el 35.3% tienen una percepción excelente de su trabajo personal. El mayor grado de satisfacción se observó durante el segundo año. Conclusión: existe un alto grado de satisfacción entre médicos residentes; sin embargo, es necesario trabajar para mejorar la satisfacción en el 20% restante.

Novel Therapeutics for Malaria.

Malaria is a potentially fatal disease caused by protozoan parasites of the genus Plasmodium. It is responsible for significant morbidity and mortality in endemic countries of the tropical and subtropical world, particularly in Africa, Southeast Asia, and South America. It is estimated that 247 million malaria cases and 619,000 deaths occurred in 2021 alone. The World Health Organization's (WHO) global initiative aims to reduce the burden of disease but has been massively challenged by the emergence of parasitic strains resistant to traditional and emerging antimalarial therapy. Therefore, development of new antimalarial drugs with novel mechanisms of action that overcome resistance in a safe and efficacious manner is urgently needed. Based on the evolving understanding of the physiology of Plasmodium, identification of potential targets for drug intervention has been made in recent years, resulting in more than 10 unique potential anti-malaria drugs added to the pipeline for clinical development. This review article will focus on current therapies as well as novel targets and therapeutics against malaria.

Androgen receptor amplification in mesonephric remnants.

Mesonephric remnants (MRs) are embryonic vestiges most commonly found in female pathology specimens from the lateral wall of the cervix. The highly regulated genetic programme of mesonephric duct development has been well characterised in animals based on traditional surgical castration and knockout mouse experiments. However, the process is incompletely understood in humans. MRs are believed to give rise to mesonephric neoplasms, which are rare tumours with uncertain pathophysiology. There is a dearth of molecular studies on mesonephric neoplasms in part due to their rarity. Here, we report the results of next-generation sequencing of MR, which identified amplification of the androgen receptor gene for the first time to the best of our knowledge and discuss the potential implications in the context of the literature.

[Cost-effectiveness of treatment of type 2 diabetes mellitus in México]. / Costo-efectividad del tratamiento de la diabetes mellitus tipo 2 en México.

Background: Type 2 Diabetes Mellitus (DM2) is a public health and socioeconomic problem, generating direct medical costs for its treatment. Objective: To analyze the cost-effectiveness of monotherapy and bitherapy treatments in patients with DM2. Methods: Cost-effectiveness, observational, ambispective, cross-sectional and analytical analysis of files in a first level medical unit. The data in the cost matrix was executed with the Office Excel 2010 program; the most prescribed drug was identified and compared with monotherapy and bitherapy. Results: The annual direct medical costs of the total population were drug cost $118,561.70MN, hospitalization cost $243,756.00MN, consultation cost $327,414.00MN and clinical trial cost $2416.79MN, obtaining an annual total of $692,148.58MN. metformin was the most indicated in monotherapy (88.4%) and as standard therapy it has higher cost-effectiveness compared to glibenclamide. In bitherapy it was metformin/glibenclamide (35.7%) versus the therapeutics of metformin/NPH insulin, metformin/insulin glargine and metformin/dapagliflozin, which had a better cost-effective result, with an incremental cost effectiveness of -$1,128,428.50MN, -$34,365.00 MN, -$119,848.97MN respectively. Conclusions: Metformin presented a better cost-effectiveness ratio in monotherapy, while in bitherapy it was the metformin/NPH insulin association.

Introducción: La Diabetes Mellitus tipo 2 (DM2) es un problema de salud pública y socioeconómico, tanto por su alta incidencia como por la generación de los costos médicos directos para su tratamiento. Objetivo: Analizar el costo-efectividad de los tratamientos en monoterapia y biterapia en pacientes con DM2. Métodos: Análisis costo-efectividad, observacional, ambispectivo, transversal y analítico. Análisis de expedientes en una unidad médica de primer nivel. Se ejecutaron los datos en la matriz de costos con el programa Office Excel 2010; se identificó el fármaco más prescrito, se comparó con monoterapia y biterapia. Resultados: Los costos médicos directos anuales del total de la población fueron: costo del medicamento $118,561.70MN, costo por hospitalización $243,756.00MN, costo por consultas $ 327,414.00MN y costo por estudios clínicos $2416.79MN, obteniendo un total anual de $692,148.58MN. La metformina fue la más indicada en monoterapia (88.4%) y como terapéutica estándar tiene mayor costo-efectividad comparada con la glibenclamida. En biterapia fue metformina/glibenclamida (35.7%) versus las terapéuticas de metformina/insulina NPH, metformina/insulina glargina y metformina/dapagliflozina, las cuales tuvieron un resultando más costo-efectivo, con un costo efectividad incremental de -$1,128,428.50MN, -$34,365.00MN, -$119,848.97MN respectivamente. Conclusiones: La metformina presento mejor relación costo efectividad en monoterapia, mientras que en biterapia fue la asociación metformina/Insulina NPH.

Central Centrifugal Cicatricial Alopecia Associated With PDL1 Loss and Increased Expression of Caspase 3: A Case Series.

ABSTRACT: Central centrifugal cicatricial alopecia (CCCA) is a scarring alopecia that disproportionately affects patients with skin of color. Genetic studies have revealed that approximately 30% of CCCAs are associated with peptidyl arginine deiminase 3 misfolding mutations. Patients with CCCA usually have a poor prognosis with progressive and permanent hair loss. To further characterize CCCA, we evaluated the inflammatory milieu, PDL1, and caspase 3 expression. The data support the idea of CCCA being a CD4-predominant T-cell process. The loss of PDL1 and increase in caspase 3 expression raises the possibility of involvement of the PD1/PDL1 pathway in CCCA.

Allelic Variant of Armadillo Repeat Containing Protein 5 (ARMC5) in Myelolipoma Mimicking Pheochromocytoma: A Case Report.

Adrenal myelolipomas are benign adrenocortical tumors composed of adipose tissue mixed with hematopoietic precursor cells. An association of myelolipoma with adrenal cortical adenoma is rare and the pathogenesis of these tumors remains unclear. Here we present a case of an incidentally discovered adrenal tumor with radiologic characteristics of a myelolipoma who underwent adrenalectomy due to biochemical suspicion for pheochromocytoma. The final pathology, however, revealed a myelolipoma with a co-existing adrenal cortical adenoma without evidence of pheochromocytoma. Genetic analysis revealed the presence of a hitherto unreported heterozygous variant, c.329C>A (p.Ala110Asp), of the armadillo repeat-containing protein 5 (ARMC5) gene which when inactivated is commonly associated with bilateral adrenal nodularity.

KRAS G12D mutation in Brunner gland adenoma.

Brunner gland lesions (BGLs) encompass benign proliferations of the homonymous glands and have been designated as hyperplasia, adenoma (BGA), hamartoma or nodule. In general terms, lesions larger than 0.5 cm are considered true neoplasia with unknown malignant potential and unclear pathogenesis. Genetic alterations have seldom been reported in BGL, and include SMAD4/DPC4 and LRIG1, but not KRAS (Kirsten rat sarcoma viral oncogene homologue) to the best of our knowledge.We present the case of a man in his 60s, evaluated for iron deficiency anaemia harbouring a 1.5 cm BGA found by duodenoscopy. Immunohistochemistry failed to reveal microsatellite instability, and next-generation sequencing revealed a KRAS G12D point mutation.

Rosai-Dorfman Disease of the Rectum: Newly Identified Genetic Point Mutations and Robotic Resection.

Rosai-Dorfman disease (RDD) is a rare disease characterized by histiocytic proliferation which typically presents as massive, painless, cervical lymphadenopathy in children or young adults. GI involvement is exceedingly rare with only 20 documented cases to date. Of those 20 cases, only 3 cases have involved the rectum. Here, we present 2 cases of rectal RDD with attention paid to the diagnostic and technical challenges presented by this disease. When presenting as a perirectal mass, RDD can be mistaken for other lesions to include malignancy, leading to surgical removal. We present a video of a robotic low-anterior resection with intracorporeal anastomosis in order to remove a pelvic mass involving the rectum, initially considered to be a stromal tumor. In addition, we describe a copy number variation in AKT and 3 point mutations detected by next generation sequencing, which had not been previously reported in association with this disease.

The prevalence and clinical significance of HER2 expression in prostate adenocarcinoma.

AIMS: Abnormalities in HER2 are well-established oncogenic drivers and are approved therapeutic targets in various malignancies. Prior studies evaluating HER2 expression in prostate cancer (PCa) have yielded variable results. Most of these studies used immunohistochemistry scoring systems based on breast cancer data. The goal of this study was to determine the prevalence and clinical significance of HER2 expression using a scoring system that better reflects the HER2 staining pattern observed in PCa. METHODS: We randomly selected similar numbers of localized low risk (AJCC stage I), locally advanced (AJCC stages II & III), and metastatic (AJCC stage IV) PCa patients treated at the DC VA Medical Center between 2000 and 2022. Among them, we included patients who had sufficient PCa tissue samples and clinical information required for this analysis. Two experienced pathologists independently scored HER2 expression (Ventana Pathway anti-HER2) according to a modified gastric cancer HER2 scoring system. RESULTS: Out of the 231 patients included, 85 % self-identified as Black. 58.9 % of patients expressed HER2 (1+: 35.5 %; 2+: 18.2 %; 3+: 5.2 %). Validity of the results was confirmed using the HercepTest antibody. Higher HER2 expression was associated with a higher Gleason Score/Grade Group and advanced disease. CONCLUSIONS: Our findings support the adverse prognostic impact on HER2 in PCa. We propose the use of a modified scoring system to evaluate HER2 expression in PCa. The observed high prevalence of HER2 expression supports the consideration of novel HER2-targeted therapies addressing even low levels of HER2 expression in future PCa trials.

Neurothekeoma With PI3K w552*, ALK P1469S, SMO G461S, and ERBB3 L77M Genetic Alterations.

ABSTRACT: Neurothekeoma, a lesion of possible fibrohistiocytic origin, is a rare, benign, superficial soft tissue tumor, histologically subclassified in 3 types: myxoid, cellular, or mixed. It clinically presents as a solitary, pink to brown nodule, ranging from 0.3 to 2.0 cm. Four point mutations (PI3K w552*, ALK P1469S, SMO G461S, and ERBB3 L77M) were identified by next-generation sequencing of a neurothekeoma presenting in the left inner thigh of a 53-year-old man. We highlight novel genetic alterations (SMO G461S and ERBB3 L77M) and previously known mutations (PI3KCA w552* and ALK P1469S) that play a role in other pathogenic pathways, but to the best of our knowledge, these have not yet been reported in neurothekeoma.

Effects of a Modern Kefir on Conditions Associated with Moderate Severe Spastic Quadriparesis Cerebral Palsy.

Cerebral palsy (CP) in children constitutes a set of movement and body posture disorders caused by brain injury, which in turn is associated with a series of intestinal, respiratory, and malnutrition conditions. Twenty-four children were selected and included for the present study and subdivided into two groups: (1) children who included modern kefir (containing 12 probiotic species) in their diet; and (2) control group (not including kefir in their diet). The group supplemented with modern kefir received a beverage with multi probiotic species and the control group received commercial yogurt (which included the 2 typical lactic acid bacteria) for 7 weeks. Anthropometric variables, resting energy expenditure, presence, and diagnosis of functional digestive disorders (FDD), frequency of respiratory problems, presence of elevated C-reactive protein, differential count of leukocytes were evaluated. A significant increase in weight and height was found in the kefir group at the final time point. In addition, kefir intake promoted a significant reduction in functional constipation and stool hardness and increased the absolute value of blood lymphocytes. Since the fermented milk beverage modern kefir improves constipation, which is the most important FDD in children with CP and the nutritional and immune status, it could be considered an important strategy to improve health in these children.

Concurrent Waldenstrom's Macroglobulinemia and Myelodysplastic Syndrome with a Sequent t(10;13)(p13;q22) Translocation.

Myelodysplastic syndromes (MDS) and Waldenstrom's macroglobulinemia (WM) are rarely synchronous. Ineffective myelopoiesis/hematopoiesis with clonal unilineage or multilineage dysplasia and cytopenias characterize MDS. Despite a myeloid origin, MDS can sometimes lead to decreased production, abnormal apoptosis or dysmaturation of B cells, and the development of lymphoma. WM includes bone marrow involvement by lymphoplasmacytic lymphoma (LPL) secreting monoclonal immunoglobulin M (IgM) with somatic mutation (L265P) of myeloid differentiation primary response 88 gene (MYD88) in 80-90%, or various mutations of C-terminal domain of the C-X-C chemokine receptor type 4 (CXCR4) gene in 20-40% of cases. A unique, progressive case of concurrent MDS and WM with several somatic mutations (some unreported before) and a novel balanced reciprocal translocation between chromosomes 10 and 13 is presented below.