Follow-up biopsies identify high rates of persistent rejection in pediatric kidney transplant recipients after treatment of T cell-mediated rejection.

BACKGROUND: Incomplete resolution of T cell-mediated rejection (TCMR) after treatment may not be detected with serum creatinine monitoring and is associated with donor-specific antibodies and chronic rejection. We evaluate the utility of follow-up biopsies (FUB) to identify and characterize rates of persistent TCMR after treatment in pediatric kidney transplant patients. METHODS: Patients from two pediatric transplant centers performing standard of care FUB at 1.5-2 months after treatment for TCMR were included. FUB were evaluated for extent of rejection resolution (complete vs. incomplete) and grade. Clinical data at time of FUB and later were reported, where available. RESULTS: Fifty-eight patients underwent FUB, at mean of 1.7 months (SD 0.7) post-index biopsy. Rejection grade on index biopsy was Banff borderline (≥i1t1 and

Measuring the effectiveness of an integrated intervention package to improve the level of infection prevention and control: a multi-centre study in Bangladesh.

BACKGROUND: Infection prevention and control (IPC) is a critical component of delivering safe, effective and high-quality healthcare services, and eliminating avoidable healthcare-associated infections (HAIs) in health facilities, predominantly in population-dense settings such as Bangladesh. AIM: Our study aimed to assess the effect of an integrated intervention package in improving the IPC level of the health facilities in Bangladesh. METHODS: We conducted a pre-post intervention study in six district hospitals (DHs) and 13 Upazila Health Complexes (UHCs) in the six districts of Bangladesh. Baseline and endline assessments were conducted between March and December 2021 using the adapted World Health Organization Infection Prevention and Control Assessment Framework (WHO-IPCAF) tool. The IPCAF score, ranging from 0-800, was calculated by adding the scores of eight components, and the IPC promotion and practice level was categorized as Inadequate (0-200), Basic (201-400), Intermediate (401-600) and Advanced (601-800). The integrated intervention package including IPC committee formation, healthcare provider training, logistics provision, necessary guidelines distribution, triage/flu corners establishment, and infrastructure development was implemented in all facilities. RESULTS: The average IPCAF score across all the facilities showed a significant increase from 16% (95% CI: 11.5-20.65%) to 54% (95% CI: 51.4-57.1%). Overall, the IPCAF score increased by 34 percentage points (P<0.001) in DHs and 40 percentage points (P<0.001) in UHCs. Following the intervention, 12 (three DHs, nine UHCs) of 19 facilities progressed from inadequate to intermediate, and another three DHs upgraded from basic to intermediate in terms of IPC level. CONCLUSION: The integrated intervention package improved IPCAF score in all facilities.

Enhancing Diabetes Care in LMICs: Insights from a Multinational Consensus.

The International Cardio-Metabolic Forum held a plenary session to establish a multinational consensus on the challenges faced in diabetes management within lower-middle-income countries (LMICs) and their potential solutions. Stakeholders, including patients, family/caretakers, healthcare professionals, and healthcare policymakers & organizations, participated in discussions. The audience of 280 doctors from 15 different countries (Pakistan, Qatar, Sri Lanka, Kenya, Myanmar, Georgia, Nigeria, Philippines, Uzbekistan, Iraq, Tanzania, Cambodia, Kazakhstan, South Sudan and Libya) was divided into 4 groups led by Group Leaders to represent each stakeholder group. Questionnaires addressing key challenges and solutions specific to each group were used to facilitate consensus development. Participants voted on relevant options based on their clinical experience. SLIDO software was used for polling, generating separate results for each group. The insights shared by healthcare professionals highlighted the importance of improving medication accessibility and cost-effectiveness for patients, emphasizing the need for adherence to treatment plans and lifestyle modifications. The significance of balanced nutrition with low glycemic index food for enhancing quality of life was recognized. Caregivers of diabetic patients with comorbidities face increasing demands for care, particularly in relation to age-related milestones. Healthcare professionals emphasized the challenges posed by cultural beliefs and health awareness, underscoring the importance of teamwork and early referral for managing comorbidities. Healthcare policymakers need to focus on disease education, awareness programs, screening guidelines, and advocacy for community and clinical screening. By addressing these challenges, a more comprehensive and effective approach to diabetes management can be achieved in LMICs, ultimately improving outcomes for individuals with diabetes.

Solitary Fibrous Tumor of Breast and Axilla: Clinicopathological Profile of Five Tumors With Comparison of Risk Stratification Models.

Introduction: Solitary fibrous tumor (SFT) is a fibroblastic tumor with malignant potential that is underpinned by a recurrent inv12(q13q13)-derived NAB2::STAT6 fusion. Breast and axilla are uncommon locations for this entity. Methods: Records of two academic institutions were electronically searched for breast and axillary SFTs. Clinical and pathologic data were reviewed. Literature review for breast or axillary SFTs was performed. Present study and previously reported tumors were stratified using five SFT risk models: original and modified Demicco metastatic risk, Salas local recurrence risk, Salas metastatic risk, and Thompson local recurrence risk. Results: Five patients with breast or axillary SFT were identified. Median age was 49 years, and median follow-up (available for four patients) was 82 months. Three patients showed no evidence of disease, and one developed recurrence. Literature review identified 58 patients with breast or axillary SFT. Median age was 54 years, and median follow-up (available for 35 patients) was 24 months. Thirty-one patients showed no evidence of disease, three developed recurrence, and one developed metastasis. Original and modified Demicco models and Thompson model showed the highest sensitivity; original and modified Demicco models and Salas metastatic risk model demonstrated the highest specificity. Kaplan-Meier models were used to assess recurrence-free probability (RFP). Original and modified Demicco models predicted RFP when stratified by "low risk" and "moderate/intermediate and high risk" tumor, though sample size was small. Conclusions: While many SFTs of breast and axilla remain indolent, a subset may develop recurrence and rarely metastasize. The modified Demicco risk model demonstrated optimal performance characteristics.

ERBB2 Amplification and HER2 Expression in Salivary Duct Carcinoma: Evaluation of Scoring Guidelines and Potential for Expanded Anti-HER2 Therapy.

Salivary duct carcinoma (SDC) is aggressive with limited therapeutic options. A subset of SDC display human epidermal growth factor receptor 2 (HER2) protein overexpression by immunohistochemistry, and some show ERBB2 gene amplification. Guidelines for HER2 scoring are not firmly established. Recent advances in breast carcinoma have established a role for anti-HER2 therapies in lesions with low HER2 expression lacking ERBB2 amplification. Delineating HER2 staining patterns in SDC is critical for evaluating anti-HER2 treatments. In total, 53 cases of SDC resected at our institution between 2004 and 2020 were identified. Androgen receptor (AR) and HER2 immunohistochemistry and ERBB2 fluorescence in situ hybridization were performed in all cases. AR expression was scored for percentage positive cells and categorized as positive (>10% of cells), low positive (1%-10%), or negative (<1%). HER2 staining levels and patterns were recorded, scored using 2018 ASCO/CAP guidelines, and categorized into HER2-positive (3+ or 2+ with ERBB2 amplification), HER2-low (1+ or 2+ without ERBB2 amplification), HER2-very low (faint staining in <10% of cells), or HER2-absent types. Clinical parameters and vital status were recorded. Median age was 70 years, with a male predominance. ERBB2-amplified tumors (11/53; 20.8%) presented at lower pT stages (pTis/pT1/pT2; P = .005, Fisher exact test) and more frequently had perineural invasion (P = .007, Fisher exact test) compared with ERBB2 nonamplified tumors; no other pathologic features differed significantly by gene amplification status. In addition, 2+ HER2 staining by 2018 ASCO/CAP criteria was most common (26/53; 49%); only 4 cases (8%) were HER2-absent status; 3+ HER2 staining was found in 9 tumors, and all were ERBB2 amplified. Six patients with HER2-expressing tumors received trastuzumab therapy, including 2 with ERBB2-amplified tumors. Overall survival and recurrence-free survival did not differ significantly based on ERBB2 status. This work suggests that 2018 ASCO/CAP guidelines for HER2 evaluation in breast carcinoma could be applied to SDC. Our findings also show broad overexpression of HER2 in SDC raising the possibility that more patients may benefit from anti-HER2-directed therapies.

Low-grade adenosquamous carcinoma of the breast: a clinical, morphological and immunohistochemical analysis of 25 patients.

AIMS: Due to its rarity and non-specific clinical and pathological features, low-grade adenosquamous carcinoma (LGASC) of the breast continues to pose diagnostic challenges. Unlike other triple-negative breast carcinomas, LGASC tends to have an indolent clinical behaviour. It is essential to recognise this lesion for accurate diagnosis and appropriate management. METHODS AND RESULTS: Twenty-five cases of LGASC were identified in our archives and collaborating institutes. Cases of LGASC with dominant coexisting other type carcinomas were excluded. We studied the clinical presentation, morphological features, patterns of the commonly used immunohistochemical stains and follow-up. In our cohort, LGASC was commonly located at the outer aspect of the breast and associated with intraductal papilloma. The morphology of LGASC is characterised by infiltrating small glands and nests with variable squamous differentiation. We also found cuffing desmoplastic (fibrolamellar) stromal change in 75% of patients and peripheral lymphocytic aggregates in 87.5% of patients. P63 and smooth muscle myosin (SMM) were the most common myoepithelial markers used to assist in diagnosis. P63 often stained peripheral tumour cells surrounding invasive glands (circumferential staining in 80% of the cases), mimicking myoepithelial cells. It also stained the small nests with squamous differentiation. However, SMM was negative in 63% of the cases. The vast majority of our cases were triple-negative; only a few had focal and weak expressions of ER and PR. One patient who did not have excision developed lymph node metastasis. Most patients underwent excision or mastectomy with negative margins as surgical treatment; there were no recurrences or metastases in these patients with clinical follow-ups up to 108 months. CONCLUSIONS: LGASC has some unique, although not entirely specific, morphological features and immunohistochemical staining patterns. Fibrolamellar stromal change, peripheral lymphocytic aggregates and variable staining of p63 and SMM are valuable features to facilitate the diagnosis.

Ocular morbidity and co-morbidities in children attending a nodal district early intervention center in Uttar Pradesh.

Purpose: To obtain epidemiological data on children with ocular morbidity attending a nodal district early intervention center (DEIC). Methods: : After parental consent, we recruited children with ocular morbidity. After detailed history and clinical evaluation, along with pediatric consultation and relevant neuro-radiological and ancillary investigation, information was entered in a pretested proforma: especially looking for perinatal morbidity, including developmental delay (DD). Visual acuity (VA) was assessed by age-appropriate means by an ophthalmic assistant trained to work with children with special needs. We diligently looked for strabismus and performed dilated ophthalmoscopy. Using JASP, we summarized data as means and proportions and reported 95% CIs. We explored the association of disability percentage with possible predictor variables using regression. Results: We enrolled 320 children, with a mean age of 34.43 ± 31.35 months; two-thirds were male; one-third belonged to lower socioeconomic status (36%), with most parents being illiterate. The mean presenting VA was 1.8 logMAR for both eyes, range: 0 to 3. Sixty-one percent were hyperopic and 27% were myopic. High refractive error, (>±6D) occurred in nine; anisometropia in one; strabismus in 149, mostly esotropia; congenital cataract in 25, whereas 63 had abnormal fundus. Seventy-six received a diagnosis of cerebral visual impairment (CVI). On multivariate linear regression (MLR), younger age, presence of DD, and CVI significantly predicted a higher disability percentage. Logistic regression revealed that statutory disability is likely associated with DD (odds ratio [OR]:13.43); whereas older age was protective (OR: 0.977). Conclusion: Our study suggests that in DEIC children with ocular morbidity, younger children, and the presence of DD significantly predict both greater disability and the likelihood of statutory levels.

Perspectives on Using Fast-Dissolving Paracetamol for Mild-to-Moderate Pain Management in Elderly or Diabetic Patients with Delayed Gastric Emptying Rates: An Exploratory Study.

Purpose: Pain is considered a major clinical and socioeconomic problem worldwide. Delayed gastric emptying rates allegedly influence the suitability of pain-relief medications in patient populations such as the elderly and individuals with diabetes. Faster pain relief was reportedly achieved by using a fast-dissolving paracetamol (FD-APAP) formulation. This study aims to gain insights to healthcare professionals' (HCPs) perspectives towards using FD-APAP in addressing barriers of pain relief in patient populations susceptible to delayed gastric emptying rates. Patients and Methods: A two-step modified Delphi consensus study was conducted among a panel of 10 general practitioners (GPs) and four endocrinologists. The first step comprises in-depth discussions around evidence relevant to FD-APAP for pain management in patient populations with delayed gastric emptying rates (elderly/diabetics). The second step (a survey) was based on the summarized input from the first step. Consensus was accepted upon ≥70% agreement. Perspectives on pain management by FD-APAP for elderly patients were explored among GPs, while those for diabetic patients were explored among GPs and endocrinologists. Results: Consensus was achieved, whereby all panel members found FD-APAP to be favorable and relevant for pain management in the elderly and the diabetic patient populations. GPs additionally raised the consensus on the importance of considering comorbidities associated with diabetes while having minimal complications during pain management. Conclusion: The panel found the faster disintegration and absorption of FD-APAP relevant and useful for patients with delayed gastric emptying, wherein, pain in the elderly and those with diabetes could be treated effectively with limited side-effects.

[Translated article] Implementation of a rapid recovery protocol in total knee arthroplasty. A randomised controlled trial.

BACKGROUND: Rapid recovery (RP) in total knee arthroplasty may increase the functionality while reducing costs. The aim of this study is to prove the benefits of a rapid recovery programme compared to our classic protocol. PATIENTS AND METHODS: We performed a RCT (NCT03823573) in patients undergoing otal knee arthroplasty. Intervention group (RP protocol) received local infiltration of levo-bupivacaine in the periarticular tissue and supervized ambulation 4-6h after surgery. Control (C) group received a femoral nerve block with levo-bupivacaine, while a drain was used. Ambulation after its removal. All the patients completed an Oxford Knee Score prior to surgery and 6 months after discharge. An ecodoppler to assess the presence of deep vein thrombosis was made 1 month after discharge. Minimum follow-up was of 6 months. RESULTS: A total of 175 patients were included in the trial (92 patients in the control group, 83 patients in the RP group). There were no differences in sex, age, implanted prosthesis, haemoglobin drop, need for transfusion, range of motion on discharge (C: 82.6°, RP: 85°) and at the end of the follow-up (C: 105.1, RP: 106.6), Oxford knee score improvement (C: 17.5 points; RP: 19.3 points), patient satisfaction or re-admissions at the emergency department (C: 7.6%; RP: 10.8%). Significancy was found on time of ischaemia (C: 81.29min; RP: 85.35min; p=.03), need for morphine shots (C: 19.7%; RP: 38.6%; p=.007), hospital stay (C: 3.84 days; RP: 2.54 days, p<.0001) and time until ambulation (C: 2.46 days; RP: 0.23 days; p<.0001). CONCLUSION: Rapid recovery protocols can reduce hospital stay without increasing complications or need for re-admission.

Quality Issues in Diagnostic Immunohistochemistry in Breast Pathology.

Immunohistochemistry techniques have been incorporated into surgical pathology for nearly a half-century and have since become intimately intertwined with its practice. In the realm of breast pathology, immunohistochemistry serves several purposes, including providing crucial prognostic and predictive data. Among its other applications, assessment of stromal invasion and establishment of mammary origin are crucial from a diagnostic standpoint. In these regards, sole reliance on immunohistochemistry may lead to misdiagnosis. In this review, we highlight pitfalls of immunohistochemistry commonly encountered in the practice of breast pathology and emphasize the importance of careful histopathological evaluation.

Spatial interplay of lymphocytes and fibroblasts in estrogen receptor-positive HER2-negative breast cancer.

In estrogen-receptor-positive, HER2-negative (ER+HER2-) breast cancer, higher levels of tumor infiltrating lymphocytes (TILs) are often associated with a poor prognosis and this phenomenon is still poorly understood. Fibroblasts represent one of the most frequent cells in breast cancer and harbor immunomodulatory capabilities. Here, we evaluate the molecular and clinical impact of the spatial patterns of TILs and fibroblast in ER+HER2- breast cancer. We used a deep neural network to locate and identify tumor, TILs, and fibroblasts on hematoxylin and eosin-stained slides from 179 ER+HER2- breast tumors (ICGC cohort) together with a new density estimation analysis to measure the spatial patterns. We clustered tumors based on their spatial patterns and gene set enrichment analysis was performed to study their molecular characteristics. We independently assessed the spatial patterns in a second cohort of ER+HER2- breast cancer (N = 630, METABRIC) and studied their prognostic value. The spatial integration of fibroblasts, TILs, and tumor cells leads to a new reproducible spatial classification of ER+HER2- breast cancer and is linked to inflammation, fibroblast meddling, or immunosuppression. ER+HER2- patients with high TIL did not have a significant improved overall survival (HR = 0.76, P = 0.212), except when they had received chemotherapy (HR = 0.447). A poorer survival was observed for patients with high fibroblasts that did not show a high level of TILs (HR = 1.661, P = 0.0303). Especially spatial mixing of fibroblasts and TILs was associated with a good prognosis (HR = 0.464, P = 0.013). Our findings demonstrate a reproducible pipeline for the spatial profiling of TILs and fibroblasts in ER+HER2- breast cancer and suggest that this spatial interplay holds a decisive role in their cancer-immune interactions.

Risk of malignancy associated with diagnostic categories of the proposed World Health Organization International System for Reporting Pancreaticobiliary Cytopathology.

BACKGROUND: The World Health Organization (WHO) has proposed an updated international classification system for reporting pancreaticobiliary cytology. Substantial changes to the prior Papanicolaou Society of Cytopathology (PSC) system have been recommended. Chiefly, the "neoplastic: benign" and "neoplastic: other" categories have been replaced by 2 new categories-"pancreatic neoplasia-low-grade" (PaN-Low) and "pancreatic neoplasia-high-grade" (PaN-High)-stratifying neoplastic mucinous cysts by cytological atypia. Low-grade malignancies are placed in the "malignant" category and benign serous cystadenoma in the "benign/negative" category. Risk of malignancy (ROM) associated with the diagnostic categories of the WHO system has yet to be defined. METHODS: All patients who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for a pancreatic lesion at a single institution from January 2016 to December 2016, prospectively classified using the PSC system, were reclassified using the WHO system. Absolute ROM was determined by histologic outcome and/or clinical follow-up of at least 6 months. RESULTS: A total of 334 EUS-FNA samples from 322 patients were reviewed and reclassified. Absolute ROM for the WHO system was 7.7% for "insufficient/inadequate/nondiagnostic" category, 1.0% for "benign/negative for malignancy," 28.0% for "atypical," 4.8% for "PaN-Low," 60.0% for "PaN-High," 100% for "suspicious for malignancy," and 100% for "malignant;" the absolute ROM for the same cohort using the PSC system was 7.7% for "nondiagnostic" category, 1.0% for "negative (for malignancy)," 28.0% for "atypical," 0.0% for "neoplastic: benign," 30.3% for "neoplastic: other," 100% for "suspicious (for malignancy)," and 100% for "positive or malignant." CONCLUSIONS: The WHO international system achieves improved stratification by associated ROM compared to the PSC system.

Papillary Breast Tumors: Continuing Controversies and Commentary on WHO's 2019 Criteria and Classification.

The category of papillary breast tumors includes a limited number of entities. Nonetheless, this relatively uncommon group of tumors seems to instigate a disproportionate degree of diagnostic disquiet. As a group, papillary breast tumors suffer from a relatively high rate of discordant interpretation. The latter is due to the inherent complexity of the lesions compounded by conflicting criteria as well as simmering controversies. For instance, "encapsulated" papillary carcinoma remains contentious with regards to whether these are noninvasive or not, and the assessment of the extent of the invasive versus noninvasive components in many solid papillary carcinomas can be problematic. The latest classification system of breast tumors enunciated by the World Health Organization (WHO), that is, Breast Tumors, which appeared in 2019, mainly sought to incorporate advances in basic and clinical sciences into diagnostic criteria for the entire spectrum of breast neoplasms-including papillary ones. The latter category of tumors is discussed at some length in Breast Tumors; however, it still appears to suffer from some lack of clarity in its subclassification. It is our intent in this communication to provide an overview of the controversies around papillary breast tumors, and offer comments on its coverage in Breast Tumors-so that any tangible or perceived ambiguities therein could be addressed in its next edition.

Implementation of a rapid recovery protocol in total knee arthroplasty. A randomized controlled trial. / Implantación de un protocolo de recuperación precoz en artroplastia total de rodilla. Ensayo clínico aleatorizado.

BACKGROUND: Rapid recovery (RP) in total knee arthroplasty may increase the functionality while reducing costs. The aim of this study is to prove the benefits of a rapid recovery program compared to our classic protocol. PATIENTS AND METHODS: We performed a RCT (NCT03823573) in patients undergoing otal knee arthroplasty. Intervention group (RP protocol) received local infiltration of levo-bupivacaine in the periarticular tissue and supervized ambulation 4-6h after surgery. Control (C) group received a femoral nerve block with levo-bupivacaine, while a drain was used. Ambulation after its removal. All the patients completed an Oxford Knee Score prior to surgery and 6 months after discharge. An ecodoppler to assess the presence of deep vein thrombosis was made one month after discharge. Minimum follow-up was of 6 months. RESULTS: A total of 175 patients were included in the trial (92 patients in the control group, 83 patients in the RP group). There were no differences in sex, age, implanted prosthesis, hemoglobin drop, need for transfusion, range of motion on discharge (C: 82.6°, RP: 85°) and at the end of the follow-up (C: 105.1, RP: 106.6), Oxford Knee Score improvement (C: 17.5 points; RP: 19.3 points), patient satisfaction or re-admissions at the emergency department (C: 7.6%; RP: 10.8%). Significancy was found on time of ischemia (C: 81.29min; RP: 85.35min; P=0.03), need for morphine shots (C: 19.7%; RP: 38.6%; P=0.007), hospital stay (C: 3.84 days; RP: 2.54 days, P<0.0001) and time until ambulation (C: 2.46 days; RP: 0.23 days; P<0.0001). CONCLUSION: Rapid recovery protocols can reduce hospital stay without increasing complications or need for re-admission.