Resumen: Consenso internacional para la nomenclatura y clasificación de la válvula aórtica bicúspide congénita y su aortopatía, con fines clínicos, quirúrgicos, intervencionistas y de investigación / Summary: International consensus statement on nomenclature and classification of the congenital bicuspid aortic valve and its aortopathy, for clinical, surgical, interventional and research purposes

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Abstract This consensus of nomenclature and classification for congenital bicuspid aortic valve and its aortopathy is evidence-based and intended for universal use by physicians (both pediatricians and adults), echocardiographers, advanced cardiovascular imaging specialists, interventional cardiologists, cardiovascular surgeons, pathologists, geneticists, and researchers spanning these areas of clinical and basic research. In addition, as long as new key and reference research is available, this international consensus may be subject to change based on evidence-based data1.

Diagnostic approach and monitoring of chronic kidney disease in the primary care pediatric population / Abordaje diagnóstico y seguimiento de la enfermedad renal crónica en la población pediátrica desde la atención primaria en salud

Abstract Chronic kidney disease (CKD) has severe consequences on the quality and expectancy of life and is considered a major health problem worldwide. This is, especially relevant in pediatric patients, as they have unique characteristics and a mortality rate 30 times higher (in advanced stages) than healthy people. This review aims to define the minimum components for the diagnostic approach and monitoring of CKD in the pediatric population from primary health care to promote comprehensive care and adequate risk management. For this purpose, we performed a systematic review of the literature with a panel of experts. Based on the evidence, to optimize the definition, diagnosis, and timely treatment of CKD in the pediatric population, we formulated 21 recommendations. These were approved by the research team and peer-reviewed by clinical experts. They will facilitate the definition of the diagnostic approach for CKD in the pediatric population in primary health-care settings, allowing for timely treatment intervention, comprehensive care, and monitoring of this disease.

Resumen La enfermedad renal crónica (ERC) tiene graves consecuencias en la calidad y la esperanza de vida, y se considera un importante problema de salud a nivel mundial. Esto es especialmente relevante en pacientes pediátricos, ya que presenta características únicas y una tasa de mortalidad en etapas avanzadas que es 30 veces mayor que en personas sanas. El objetivo de esta revisión fue definir los componentes mínimos para el abordaje diagnóstico y para el seguimiento de la ERC en la población pediátrica desde la atención primaria en salud, con el fin de promover la atención integral y una adecuada gestión del riesgo. Para esto, se realizó una revisión sistemática de la literatura con panel de discusión de expertos. Basándonos en la evidencia, y con el objetivo de optimizar la definición, diagnóstico y tratamiento oportuno de la ERC en la población pediátrica, se formularon 21 recomendaciones. Estas fueron aprobadas por el equipo desarrollador y los pares expertos clínicos evaluadores, y permitirán definir de manera oportuna el abordaje diagnóstico de la ERC en la población pediátrica desde la atención primaria en salud, facilitando la intervención temprana, una atención integral y el seguimiento de esta patología.

Smoking characteristics and years since quitting smoking of US adults diagnosed with lung and bladder cancer: A national health and nutrition examination survey analysis

ABSTRACT Purpose: Smoking is a recognized risk factor for bladder BC and lung cancer LC. We investigated the enduring risk of BC after smoking cessation using U.S. national survey data. Our analysis focused on comparing characteristics of LC and BC patients, emphasizing smoking status and the latency period from smoking cessation to cancer diagnosis in former smokers. Materials and Methods: We analyzed data from the National Health and Examination Survey (2003-2016), identifying adults with LC or BC history. Smoking status (never, active, former) and the interval between quitting smoking and cancer diagnosis for former smokers were assessed. We reported descriptive statistics using frequencies and percentages for categorical variables and median with interquartile ranges (IQR) for continuous variables. Results: Among LC patients, 8.9% never smoked, 18.9% active smokers, and 72.2% former smokers. Former smokers had a median interval of 8 years (IQR 2-12) between quitting and LC diagnosis, with 88.3% quitting within 0-19 years before diagnosis. For BC patients, 26.8% never smoked, 22.4% were active smokers, and 50.8% former smokers. Former smokers had a median interval of 21 years (IQR 14-33) between quitting and BC diagnosis, with 49.3% quitting within 0-19 years before diagnosis. Conclusions: BC patients exhibit a prolonged latency period between smoking cessation and cancer diagnosis compared to LC patients. Despite smoking status evaluation in microhematuria, current risk stratification models for urothelial cancer do not incorporate it. Our findings emphasize the significance of long-term post-smoking cessation surveillance and advocate for integrating smoking history into future risk stratification guidelines.

Propuesta de estrategias terapéuticas combinadas para KRAS en cáncer de pulmón de células no pequeñas a partir de análisis in silico / Proposal of combined therapeutic strategies for KRAS in non-small cell lung cancer based on an in silico analysis

RESUMEN Objetivo: Los pacientes con cáncer de pulmón de células no pequeñas positivas a la mutación del gen linfoma anaplásico quinasa (ALK+) que, además, presentan mutaciones en el gen Kirsten rat sarcoma (KRAS), como KRASG12C, están mostrando resistencia tanto a inhibidores del gen linfoma anaplásico quinasa (ALK) como de KRAS. Por ello, se analizó la interacción de los inhibidores de ALK con KRAS, para sugerir una sinergia entre ambos. Materiales y métodos: En el estudio se realizó un modelado por homología de las estructuras KRASwt, KRASG12C y ALKwt. Posteriormente, se realizaron acoplamientos moleculares para determinar la energía de unión de los inhibidores de ALK y de KRAS, y evaluar la posible interacción entre los inhibidores de ALK con KRAS y la estructura KRASG12C. Finalmente, se analizó la expresión en la vía de proliferación celular de las proteínas rat sarcoma/quinasa regulada por señales extracelulares (vía RAS/MEK) mediante la técnica de Western blot. Resultados: Los valores de energía de unión muestran la posibilidad de interacción de los inhibidores de ALKwt, como crizotinib y alectinib, con las estructuras de KRASwt y KRASG12C. Los acoplamientos entre crizotinib con KRASwt y KRASG12C, respectivamente, muestran valores de energía de interacción (42,77 kcal/mol y 46,20 kcal/mol) muy similares a los obtenidos entre crizotinib y ALK (42,37 kcal/mol). A su vez, alectinib se acopló en el mismo sitio que los fármacos específicos de KRAS y KRASG12C, y presentaron valores de energía de interacción (51,74 kcal/mol y 54,69 kcal/mol, respectivamente) superiores a los obtenidos con ALK (44,94 kcal/mol). Finalmente, la expresión de la vía RAS/MEK nos mostró una disminución significativa de la expresión de RAS en líneas celulares de cáncer de pulmón ALK+ y ALKL1196M tratadas con crizotinib y alectinib. Conclusiones: Las técnicas in silico de este estudio muestran la posibilidad de acoplamiento entre los inhibidores de ALK (crizotinib y alectinib) con la estructura de KRAS. Esto permite sugerir una posible terapia combinada entre inhibidores de KRAS y ALK para los casos de coexistencia de ambas mutaciones, que puede evaluarse en posteriores ensayos con líneas celulares.

ABSTRACT Objective: Patients with non-small cell lung cancer positive for the anaplastic lymphoma kinase (ALK+) gene mutation who also have mutations in the Kirsten rat sarcoma (KRAS) gene, such as KRAS G12C, are showing resistance to both anaplastic lymphoma kinase (ALK) gene and KRAS inhibitors. Therefore, the interaction between ALK inhibitors and KRAS was analyzed to suggest a synergy between them. Materials and methods: The study performed homology modeling of the KRASwt, KRAS G12C and ALKwt structures. Subsequently, molecular dockings were carried out to determine the binding energy of ALK and KRAS inhibitors and to evaluate the possible interaction of ALK inhibitors with KRAS and the KRAS G12C structure. Finally, the expression in the RAS/MEK pathway was analyzed using the Western Blot technique. Results: The binding energy values show the potential interaction of ALKwt inhibitors, such as crizotinib and alectinib, with the KRASwt and KRAS G12C structures. The binding of crizotinib to KRASwt and KRAS G12C, respectively, indicates interaction energy values (42.77 kcal/mol and 46.20 kcal/mol) which are very similar to those obtained between crizotinib and ALK (42.37 kcal/mol). In turn, alectinib bound to the same site as drugs targeting KRAS and KRAS G12C, and showed interaction energy values (51.74 kcal/mol and 54.69 kcal/mol, respectively) higher than those obtained with ALK (44.94 kcal/mol). Finally, a significant decrease in RAS expression within the RAS/MEK pathway was observed in ALK+ and ALK 1196M lung cancer cell lines treated with crizotinib and alectinib. Conclusions: In silico techniques of this study demonstrate the potential binding of ALK inhibitors (crizotinib and alectinib) to the KRAS structure. In addition, this allows suggesting a possible combined therapy between KRAS and ALK inhibitors for cases of coexistence of both mutations that can be assessed in subsequent trials with cell lines.

Utilidad diagnóstica del CD117 en un inusual carcinoma adenoide quístico del labio superior / Diagnostic utility of CD117 in an unusual adenoid cystic carcinoma of the upper lip / Utilidade diagnóstica do CD117 num carcinoma adenoide cístico invulgar do lábio superior

RESUMEN El carcinoma adenoide quístico (CAQ) es una neoplasia maligna de glándula salival, de evolución lenta pero de agresivo comportamiento, que se presenta frecuentemente en el paladar; sin embargo, en el labio superior, donde suelen encontrarse más neoplasias benignas, su presencia es escasamente relatada. Se expone un relato de una mujer de 63 años, derivada por presentar un nódulo en el labio superior derecho, de aspecto benigno, consistencia firme, circunscrito, móvil, doloroso a la palpación, sin tiempo de evolución determinado y cuyo estudio histopatológico exhibió una proliferación de células anguladas e hipercromáticas de escaso citoplasma, organizadas en patrón cribiforme y predominantemente tubular. Se realiza un estudio inmunohistoquímico, el cual mostró positividad para SMA, p63 y CD117 con un Ki-67 del 10 % aproximadamente. Estos resultados confirman diagnóstico de CAQ con patrón tubular, destacando el rol del CD117 para el diagnóstico diferencial con adenocarcinoma polimorfo. Se deriva a la paciente para tratamiento quirúrgico y radioterapia, y luego de un año de seguimiento mantiene un buen comportamiento clínico.

ABSTRACT Adenoid cystic carcinoma (ACCC) is a malignant neoplasm of the salivary gland, of slow evolution but aggressive behavior, which frequently occurs in the palate; however, in the upper lip, where more benign neoplasms are usually found, its presence is scarcely reported. We report the case of a 63-year-old woman, referred for presenting a nodule in the right upper lip, with benign appearance, firm consistency, circumscribed, mobile, painful to palpation, with no determined time of evolution and whose histopathological study showed a proliferation of angular and hyperchromatic cells with scarce cytoplasm, organized in a cribriform pattern and predominantly tubular. An immunohistochemical study was performed, which showed positivity for SMA, p63 and CD117 with a Ki-67 of approximately 10%. These results confirm the diagnosis of CAC with tubular pattern, highlighting the role of CD117 for the differential diagnosis with polymorphous adenocarcinoma. The patient was referred for surgical treatment and radiotherapy, and after one year of follow-up she maintained a good clinical behavior.

RESUMO O carcinoma adenoide cístico (CACC) é uma neoplasia maligna da glândula salivar, de evolução lenta, mas de comportamento agressivo, que ocorre frequentemente no palato; no entanto, a sua presença é raramente relatada no lábio superior, onde normalmente se encontram neoplasias mais benignas. Relatamos o caso de uma mulher de 63 anos que foi encaminhada por apresentar um nódulo benigno no lábio superior direito, de aspeto firme, circunscrito, móvel, doloroso à palpação, sem tempo de evolução definido. O exame histopatológico revelou uma proliferação de células angulosas e hipercromáticas com citoplasma escasso, organizadas em padrão cribriforme e predominantemente tubulares. Foi efetuado um estudo imuno-histoquímico que mostrou positividade para SMA, p63 e CD117 com um Ki-67 de aproximadamente 10 %. Estes resultados confirmam o diagnóstico de CAC com padrão tubular, realçando o papel do CD117 no diagnóstico diferencial com adenocarcinoma polimorfo. A paciente foi encaminhada para tratamento cirúrgico e radioterapia e, após um ano de seguimento, manteve bom comportamento clínico.

Schwannoma de colon derecho: a propósito de un caso / Schwannoma of the right colon: case report

RESUMEN El schwannoma de colon es una entidad sumamente rara que puede debutar como lesión subepitelial con signos ulcerativos de melena y anemia. El estudio de imágenes nos orienta a la localización mientras que la biopsia colonoscópica no es de ayuda. Muchas veces el diagnóstico y tratamiento se efectúa con la resección de la lesión en tanto que el diagnóstico final se realiza en el posoperatorio por histopatología y por la inmunohistoquímica, la cual muestra positividad intensa para S100 y vimentina en las células tumorales con un índice de proliferación KI67 menor al 1%, por lo que se concluye que se trata de una lesión benigna. Presentamos el siguiente caso por su dificultad diagnóstica pre e intraoperatoria, clínica inespecífica y diagnóstico definitivo por inmunohistoquímica.

ABSTRACT Colon schwannoma is an extremely rare entity that may debut as a subepithelial lesion with ulceration signs, such as melena and anemia. Imaging studies guide us to localization, while a colonoscopy biopsy is not helpful. Many times, the diagnosis and treatment are made with lesion resection, and the final diagnosis is postoperatively made with histopathology and immunohistochemistry, which shows intense positivity for S100 and vimentin in tumor cells with a KI67 proliferation index of less than 1%, therefore, it is concluded that this is a benign lesion. We present this case due to its pre- and intraoperative diagnostic difficulty, non-specific symptoms, and its definitive diagnosis that was achieved with immunohistochemistry.

Manual versus markerless (Image-guided system) toric intraocular lens implantation outcomes for astigmatic correction in cataract surgeries

Objective@#Toric intraocular lens implantation has been used to correct corneal astigmatism during cataract surgery. The study aimed to compare the visual outcomes between manual vs markerless toric intraocular lens implantation in astigmatic correction.@*Methods@#The medical records of patients at American Eye Center who underwent phacoemulsification by multiple surgeons with insertion of monofocal or multifocal toric lenses via manual marking and markerless method from 2010-2019 were reviewed.@*Results@#A total of 70 patients were included in the study. Results showed no significant difference in the following characteristics between manual and markerless method at one month and two months post-cataract surgery: uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), uncorrected near vision acuity (UNVA), corrected near vision acuity (CNVA), refraction spherical equivalent. The UDVA, CDVA, UNVA, CNVA and astigmatism had significantly lower median/mean-rank at one and two months postoperatively compared to preoperative values.@*Conclusion@#In conclusion, our findings indicated that both manual-based and markerless systems effectively facilitated accurate placement of the toric IOL on the desired axis. Notably, there was no significant difference observed between the two methods. Both systems are straightforward to execute. In low-resource settings like the Philippines, the manual marking method can be employed when markerless guidance equipment is unavailable.

Training needs assessment: Basis for the development of training programs for employees in a public higher institution

Background@#This research assesses the training needs of employees at the University of the Philippines Manila (UPM) to prepare a comprehensive plan and program intervention for the 2023 training calendar.@*Objectives@#This study specifically examines the reaction of the employees to the training program (Level 1), changes in the level of learning (Level 2), and transfer of training in the workplace or behavioral changes (Level 3). This TNA survey is essential to identify skill gaps, set priorities, and tailor training programs suitable to the needs of UPM employees.@*Methodology@#The study employed a quantitative survey method in assessing employees’ needs across different colleges, units, and offices using a training needs assessment (TNA) survey. A total of 382 employees were surveyed regarding their needs to enhance their core, technical, leadership, and job-specific competencies.@*Results@#Results showed that based on the varying degree of necessity, all the training programs in the training needs assessment survey were considered needed by the employees. Twelve training programs were proposed in the 2023 training calendar as a result of this TNA including three programs for improving core competencies, four programs for technical competencies, two programs for leadership competencies, and three programs for job-specific competencies. Specifically, the training focus on Stress Management, Handling Complaints and Grievances, and Safety and Emergency for core competency; Written and Spoken Communication, Google Workspace/Microsoft Office Applications, Data/Records Management for technical competency; Succession Planning and Managing People for leadership competency; and Procurement, Research Skills, and Creative Design Training for job-specific competency.@*Conclusion@#The Training Needs Assessment conducted at the University of the Philippines Manila revealed crucial areas where tailored training programs can play a transformative role in boosting workforce competence and effectiveness. The findings highlight the importance of training in areas such as stress management, decision-making, safety protocols, ethical leadership, and conflict resolution.

Incidental finding of an atypical cartilaginous tumor in an adult female with recurrent patellar dislocation: Single-stage extended curettage using freezing nitrogen ethanol composite followed by Medial Patello-Femoral Ligament Reconstruction

@#Atypical cartilaginous tumor (ACT) refers to a low-grade cartilaginous neoplasm microscopically identical to grade 1 chondrosarcoma, affecting the appendicular skeleton. Treatment with intralesional curettage has been found to provide sufficient local control with less morbidity compared to wide resection. This is the first reported case of a simultaneous medial patello-femoral ligament (MPFL) reconstruction with extended curettage for ACT on the ipsilateral femur. A 45-year-old female presented with chronic recurrent patellar dislocation of the right knee. Magnetic resonance imaging revealed a tear of the MPFL, with an incidental epi-metaphyseal chondroid lesion. After biopsy confirmed an ACT, single-stage extended curettage using freezing nitrogen ethanol composite (FNEC) and MPFL reconstruction was performed, followed by augmentation with bone cement and a distal femoral plate. Currently, the patient is independently ambulatory, with full range of motion about the knee. Following histologic confirmation of an ACT in the setting of a concurrent MCL tear, a single-stage procedure to address both conditions is a viable option that can reduce complications associated with multiple surgeries. Extended curettage using FNEC has been shown to produce good short-term oncologic outcomes while maximizing function.

The use of Levonorgestrel-releasing Intrauterine System (LNG-IUS) in the treatment of symptomatic leiomyoma uteri: A systematic review

Background@#While surgical intervention has been the usual treatment option for leiomyomas, non-surgical methods have been gaining popularity over the years. The levonorgestrel-releasing intrauterine system (LNG-IUS) is said to be effective in alleviating the signs and symptoms brought by uterine leiomyomas.@*Objective@#To determine the effectiveness of LNG-IUS in the treatment of uterine leiomyomas presenting with abnormal uterine bleeding.@*Methods@#The study was conducted using the PRISMA 2020 guidelines. The literature search was performed using the following databases: Medline, Cochrane Library, PubMed, Elsevier, Embase, and Herdin. All identified studies published from January 2015 up to July 2023 were included. Titles and abstracts were screened independently by two reviewers. Data extraction and risk of bias assessment were done independently by two reviewers. Gathered information were managed using Microsoft Excel spreadsheet. Synthesis of study characteristics and findings were conducted using a descriptive narrative review. The main outcomes were uterine volume, fibroid size, menstrual blood loss or bleeding patterns, and serum hemoglobin and hematocrit levels. Secondary outcome was incidence of adverse events.@*Results@#A total of 5 studies were included with two having low methodological quality. One before-and-after cohort study showed that the use of LNG-IUS is effective in reducing menorrhagia with improvement in hematologic parameters. There is no change, however, in uterine volume. Another cohort study showed that the intervention is safe with low incidence of severe adverse events (0.5% in 595 patients). A comparative cohort study showed that LNG-IUS significantly decreased uterine volume and fibroid size, and a good alternative for treatment of heavy menstrual bleeding, as compared to intramuscular progestogen. Another before-and-after cohort study showed a significant decrease in uterine volume in women given LNG-IUS, but not in the control group. Finally, one comparative cross-sectional study showed that LNG-IUS did not effectively reduce heavy bleeding in 32.3% of patients, compared to laparoscopic hysterectomy, which was was 100% effective.@*Conclusion@#The use of LNG-IUS resulted in reduced menstrual bleeding and improved hematologic parameters after treatment. LNG-IUS was more effective compared to other hormonal treatments. However, when compared to laparoscopic hysterectomy, LNG-IUS was less effective in managing heavy bleeding. The incidence of adverse events reported in the studies was low.

Genomics-driven derivatization of the bioactive fungal sesterterpenoid variecolin: Creation of an unnatural analogue with improved anticancer properties

A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin ( 1) and variecolactone ( 2) was identified in Aspergillus aculeatus ATCC 16872. Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB. Intriguingly, the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues ( 5- 7). Analysis of the compounds' anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities, 5 was associated with significantly reduced toxic side effects in cancer-bearing mice, indicating its potentially broader therapeutic window. Our study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.

Gestational Diabetes in Melanesia and Appropriateness of Current Screening and Diagnostic Tests

Abstract@#In low-resource settings such as Melanesia, gestational diabetes often goes undiagnosed due to many factors, including the unsuitability of current tests. Ideally a gestational diabetes test for low-resource settings should meet criteria related to acceptability, test performance and operational characteristics, with minimal impositions on individual patients or the wider health system. None of the six tests recommended in country-specific gestational diabetes guidelines in Melanesia (2-hour oral glucose tolerance test, glucose challenge test, fasting plasma glucose, random plasma glucose, 2-hour postprandial glucose and glycated haemoglobin) meet criteria related to these attributes. Additionally, each Melanesian country has different, complex algorithms that use multiple tests in different combinations. With a high and increasing burden of diabetes mellitus (and therefore assumed gestational diabetes), Melanesian health practitioners and policymakers should be aware of the limitations of recommended tests for gestational diabetes and be open to alternative technologies that may be more appropriate.

Can the Heald anal stent help to reduce anastomotic or rectal stump leak in elective and emergency colorectal surgery? A single-center experience

Anastomotic and rectal stump leaks are feared complications of colorectal surgery. Diverting stomas are commonly used to protect low rectal anastomoses but can have adverse effects. Studies have reported favorable outcomes for transanal drainage devices instead of diverting stomas. We describe our use of the Heald anal stent and its potential impact in reducing anastomotic or rectal stump leak after elective or emergency colorectal surgery. We performed a single-center retrospective analysis of patients in whom a Heald anal stent had been used to “protect” a colorectal anastomosis or a rectal stump, in an elective or emergency context, for benign and malignant pathology. Intraoperative and postoperative outcomes were reviewed using clinical and radiological records. The Heald anal stent was used in 93 patients over 4 years. Forty-six cases (49%) had a colorectal anastomosis, and 47 (51%) had an end stoma with a rectal stump. No anastomotic or rectal stump leaks were recorded. We recommend the Heald anal stent as a simple and affordable adjunct that may decrease anastomotic and rectal stump leak by reducing intraluminal pressure through drainage of fluid and gas.

Laser hemorrhoidoplasty in the treatment of symptomatic hemorrhoids: a pilot Australian study

Purpose@#Traditional therapeutic approaches to the surgical management of hemorrhoid disease such as hemorrhoidectomies are plagued with severe postoperative pain and protracted recovery. Our pilot study aims to the laser hemorrhoidoplasty (LH) patients with symptomatic hemorrhoid disease that have failed conservative management for the first time in an Australian population. @*Methods@#Thirty patients were prospectively enrolled to undergo LH. Postoperative pain, time to return to function, and quality of life (QoL) were determined through the Hemorrhoid Disease Symptom Score and Short Health Scale adapted for hemorrhoidal disease and compared to a historical group of 43 patients who underwent a Milligan-Morgan hemorrhoidectomy by the same surgeon at 3, 6, and 12 months. @*Results@#The LH group had significantly lower mean predicted pain scores on days 1 and 2 and lower defecation pain scores and lower opioid analgesia use on days 1, 2, 3, and 4. The median time to return to normal function was significantly lower in the LH group (2 days vs. 9 days, P<0.001). Similarly, the median days to return to the workplace was significantly lower in the LH group (6 days vs. 13 days, P=0.007). During long-term follow-up (12 months), hemorrhoid symptoms and all QoL measures were significantly improved, especially among those with grade II to III disease. @*Conclusion@#This pilot study demonstrates low pain scores with this revivified procedure in an Australian population, indicating possible expansion of the therapeutic options available for this common condition. Further head-to-head studies comparing LH to other hemorrhoid therapies are required to further determine the most efficacious therapeutic approach.

Total Hip Arthroplasty Outcomes before or after Renal Transplant: A Retrospective Large Cohort Analysis

Background@#While it is known that patients with end-stage renal disease (ESRD) are at an increased risk of complications following total hip arthroplasty (THA), there is a gap in the literature in comparing patients with ESRD to patients who undergo renal transplant (RT) before or after THA. This study is to address this gap by analyzing outcomes of THA in ESRD patients, RT patients, and RT candidates. @*Methods@#Using the PearlDiver Mariner database, ESRD patients, RT patients, and RT candidates undergoing primary THA were identified and compared. Multivariable logistic regression analyses were done for medical complications up to 90 days and surgical complications up to 2 years. Ninety-day emergency department (ED) visits and inpatient readmission were also documented. @*Results@#A total of 7,868 patients were included: 5,092 had ESRD, 2,520 had RT before THA, and 256 were candidates for RT. Compared to patients with ESRD, RT patients demonstrated lower rates of medical complications such as pneumonia (3.61% vs. 5.99%, p = 0.039) and transfusion (4.60% vs. 7.66%, p < 0.001). Additionally, RT patients displayed decreased rates of surgical complications, including wound complications (2.70% vs. 4.22%, p = 0.001), periprosthetic joint infection (PJI) at 1 year (2.30% vs. 4.81%, p < 0.001) and 2 years (2.58% vs. 5.42%, p < 0.001), and aseptic loosening at 2 years (0.79% vs. 1.43%, p = 0.006). Similarly, when compared to RT candidates, RT patients demonstrated a lower incidence of postoperative complications, including 1-year PJI (2.30% vs. 5.08%, p = 0.013), 2-year PJI (2.58% vs. 5.08%, p = 0.028), 1-year aseptic loosening (0.56% vs. 2.73%, p < 0.001), and 2-year aseptic loosening (0.79% vs. 2.73%, p = 0.005). RT patients also had lower rates of ED visits and hospital readmissions. @*Conclusions@#Compared to ESRD patients and RT candidates, patients with RT have a significantly lower likelihood of medical complications, PJI, aseptic hardware loosening, ED visits, and hospital readmission. Patients with ESRD on the RT waiting list should delay THA until after RT surgery. For those not eligible for RT, it is vital to take extra precautions to reduce the risk of complications.

A Contemporary Approach to the Diagnosis and Management of Adrenal Insufficiency

Adrenal insufficiency (AI) can be classified into three distinct categories based on its underlying causes: primary adrenal disorders, secondary deficiencies in adrenocorticotropin, or hypothalamic suppression from external factors, most commonly glucocorticoid medications used for anti-inflammatory therapy. The hallmark clinical features of AI include fatigue, appetite loss, unintentional weight loss, low blood pressure, and hyponatremia. Individuals with primary AI additionally manifest skin hyperpigmentation, hyperkalemia, and salt craving. The diagnosis of AI is frequently delayed due to the non-specific symptoms and signs early in the disease course, which poses a significant challenge to its early detection prior to an adrenal crisis. Despite the widespread availability of lifesaving glucocorticoid medications for decades, notable challenges persist, particularly in the domains of timely diagnosis while simultaneously avoiding misdiagnosis, patient education for averting adrenal crises, and the determination of optimal replacement therapies. This article reviews recent advancements in the contemporary diagnostic strategy and approaches to optimal treatment for AI.

Influenza Virus-Derived CD8 T CellEpitopes: Implications for the Development of Universal Influenza Vaccines

The influenza virus poses a global health burden. Currently, an annual vaccine is used to reduce influenza virus-associated morbidity and mortality. Most influenza vaccines have been developed to elicit neutralizing Abs against influenza virus. These Abs primarily target immunodominant epitopes derived from hemagglutinin (HA) or neuraminidase (NA) of the influenza virus incorporated in vaccines. However, HA and NA are highly variable proteins that are prone to antigenic changes, which can reduce vaccine efficacy. Therefore, it is essential to develop universal vaccines that target immunodominant epitopes derived from conserved regions of the influenza virus, enabling cross-protection among different virus variants. The internal proteins of the influenza virus serve as ideal targets for universal vaccines. These internal proteins are presented by MHC class I molecules on Ag-presenting cells, such as dendritic cells, and recognized by CD8 T cells, which elicit CD8 T cell responses, reducing the likelihood of disease and influenza viral spread by inducing virus-infected cell apoptosis. In this review, we highlight the importance of CD8 T cell-mediated immunity against influenza viruses and that of viral epitopes for developing CD8 T cell-based influenza vaccines.

Association of Clinical Characteristics With Familial Hypercholesterolaemia Variants in a Lipid Clinic Setting:A Case-Control Study

Objective@#Familial hypercholesterolaemia (FH) variant positive subjects have over double the cardiovascular risk of low-density-lipoprotein-cholesterol (LDL-C) matched controls. It is desirable to optimise FH variant detection. @*Methods@#We identified 213 subjects with FH gene panel reports (LDLR, APOB, PCSK9, and APOE) based on total cholesterol >310 mg/dL; excluding triglycerides >400 mg/dL, cascade screening, and patients without pre-treatment LDL-C recorded. Demographic, clinical and lipid parameters were recorded. @*Results@#A 31/213 (14.6%) patients had pathogenic or likely pathogenic FH variants. 10/213 (4.7%) had variants of uncertain significance. Compared with patients without FH variants, patients with FH variants were younger (median age, 39 years vs. 48 years), had more tendon xanthomata (25.0% vs. 11.4%), greater proportion of first degree relatives with total cholesterol >95th percentile (40.6% vs. 16.5%), higher LDL-C (median, 271 mg/dL vs. 236 mg/dL), and lower triglycerides (median, 115 mg/dL vs. 159 mg/dL). The Besseling et al. model (c-statistic 0.798) improved FH variant discrimination over Friedewald LDL-C (c-statistic 0.724), however, Dutch Lipid Clinic Network Score (DLCNS) did not (c-statistic 0.665). Sampson LDL-C (c-statistic 0.734) had similar discrimination to Friedewald. @*Conclusion@#Although tendon xanthomata and first degree relatives with high total cholesterol >95th percentile were associated with FH variants, DLCNS or Simon Broome criteria did not improve FH detection over LDL-C. Sampson LDL-C did not significantly improve discrimination over Friedewald. Although lower triglycerides and younger age of presentation are positively associated with presence of FH variants, this information is not commonly used in FH detection algorithms apart from Besseling et al.

Laparoscopic right hemicolectomy with complete mesocolic excision and D3 lymphadenectomy using the open book approach: a video vignette

According to the concept of total mesorectal excision for rectal cancer, Hohenberger translated this concept to colonic cancer by introducing complete mesocolic excision (CME). The concept of this surgical technique was further elucidated by Benz et al. in the form of an open book approach. This article presents and demonstrates in a video a case of laparoscopic right hemicolectomy with CME and D3 lymphadenectomy using open book approach in the treatment of a T3N1M0 distal ascending colonic adenocarcinoma. The final pathology report confirmed moderately differentiated adenocarcinoma with a maximum tumor size of 55 mm and 0/60 lymph nodes. The mesocolic fascia was intact and R0 was achieved. The final staging was pT3pN0pM0. However, D3 lymphadenectomy is not universally adopted due to concerns of higher morbidity we believe that with adequate training and supervision CME with D3 LDN is feasible and safe to be offered to all right-sided colorectal cancers with curative intent treatment.