Clinical Workup Research Articles

Pleomorphic Adenoma of the Submandibular Gland with Skull Metastasis: A Case Report.

Metastasizing pleomorphic adenoma is a rare entity that has the propensity for distant metastasis despite being histologically benign. We report the case of a 56-year-old woman with a long-standing right upper neck swelling and a recent-onset swelling over the left side of the scalp. Clinical workup did not reveal any other tumor deposits in the body. Complete excision of the right submandibular gland and the scalp swelling was performed. The case was diagnosed as metastasizing pleomorphic adenoma. The exact cause of the malignant manifestation of this histologically benign entity is unclear. The time of appearance of a metastatic deposit is highly variable and is usually preceded by a local recurrence. Further research on the malignant behavior of this entity is warranted.

A Lack of Joint Line Tenderness Is Consistent With a Healed Meniscus, But Positive Clinical Examination Findings and MRI Scans Are Inconsistent in Identifying Failure After Meniscal Repair: A Systematic Review and Subgroup Meta-analysis.

The number of meniscal repairs being completed each year is increasing; however, the optimal, cost-effective postoperative assessment to determine the success or failure of a meniscal repair is not well known. The purpose of this systematic review was to identify the clinical examination testing that correlates with objective magnetic resonance imaging (MRI) or second-look arthroscopy (SLA) findings to determine an optimal clinical workup for assessing postoperative meniscal repair healing. It was hypothesized that specific clinical tests would correlate with meniscal repairs that did not heal. Systematic review and meta-analysis; Level of evidence, 4. This systematic review included all clinical studies investigating meniscal repairs, meniscal repair outcomes, and meniscal healing with clinical findings, MRI, and/or SLA, published in a peer-reviewed journal and with full English text available. All included studies were evaluated for bias using the Methodological Index for Non-Randomized Studies (MINORS). The clinical tests included those using "Barrett's criteria," with the assessment of effusion, joint line tenderness, locking, McMurray testing, and radiographs. This parameter has also been abbreviated to "modified Barrett's criteria" to include only joint line tenderness, effusion, and McMurray testing. No significant correlations were found between clinical tests and MRI or SLA. A subgroup meta-analysis between Barrett's and non-Barrett's studies reported no significant subgroup differences (χ12 = 0.24; P = .62). A meta-analysis of diagnostic accuracy using a group of 7 studies that reported on true-positive, true-negative, false-positive, and false-negative data for SLA demonstrated that only a lack of joint line tenderness had a high specificity for a healed meniscal repair, with a log diagnostic odds ratio of 2.62 (95% CI, 0.47-4.76). This study found no significant correlation with any specific clinical test for meniscal repair healing status using postoperative MRI and/or SLA findings. However, it was found that no healing (when compared with complete or incomplete healing) on MRI and joint line tenderness should be considered when assessing the status of postoperative meniscal repair healing. In addition, a subgroup meta-analysis found that a lack of joint line tenderness was highly correlated with a healed meniscal repair.

Cardiopulmonary Exercise Testing: Deciphering Cardiovascular Complications in Systemic Sclerosis.

Cardiac manifestations in systemic sclerosis (SSc) are variable and are associated with a poor prognosis, frequently resulting in impaired right ventricular function and heart failure. A high proportion of patients with SSc experience pulmonary arterial hypertension (PAH), interstitial lung disease, or myocardial involvement, all of which can lead to exercise intolerance. In this context, cardiopulmonary exercise testing (CPET) is a useful tool for diagnosing exercise intolerance, elucidating its pathophysiology, and assessing its prognosis. CPET can also identify patients with SSc at higher risk of developing PAH. Despite its utility, current guidelines for CPET do not include the evaluation of patients with SSc, nor do standard SSc management guidelines consider CPET in the clinical work-up. This review summarizes the development, supporting evidence, and application of CPET in assessing cardiac involvement in patients with SSc.

Contribution of clinical, biological mini-puberty and genetic analysis in 57 46,XY DSD: a monocentric retrospective cohort

Differences of sex development (DSD) is a group of rare congenital conditions defined by chromosomal, gonadal and/or phenotypic discordance or atypical sex. The mini-puberty, corresponding to the transient postnatal activation of the hypothalamic-pituitary-gonadal axis, is an important diagnosis window in the clinical workup of infants with DSD. First objective to compare clinical data as well as hormone levels during minipuberty between patients with and without a genetic diagnose. Secondary objectives were to assess the positive predictive value of specific hormone levels at M2 , the mid-point of mini-puberty, of age to differentiate between patients with and without a genetic diagnose by NGS. Our study included 57 children with 46,XY DSD born between September 2010 and August 2022 who had results from hormone level measurements during mini-puberty and a next-generation sequencing DSD gene panel. From genetic testing, the diagnostic yield was 49%. Hormone analysis during mini-puberty demonstrated variations in anti-Müllerian hormone, inhibin B, follicle-stimulating hormone and luteinizing hormone levels, with specific patterns observed in certain DSD conditions. Notably, levels of follicle-stimulating hormone >4 IU/L, anti-Müllerian hormone <235 pmol/l, and inhibin B <189 pg/ml at 2 months of life were associated with a higher probability of a genetic diagnose. this study proposes a less invasive diagnostic approach for 46,XY DSD children with palpable gonads at birth, it seems a single blood test around the second month of life for comprehensive analysis.

KRT20-/SATB2+/MCPyV+ Sinonasal Merkel Cell Carcinoma: A Detailed Immunohistochemical and In Situ Hybridization Study.

Merkel cell carcinoma (MCC) is an uncommon aggressive neoplasm, usually arising in sun-exposed skin of the head and neck. By immunohistochemistry, KRT20 and MCPyV positivity are found in about 90% and 80% of MCCs, respectively. Noteworthy, viral status in lip/oral cavity MCCs is poorly known. A 78-year-old male was referred presenting a tumor mass on the right maxilla four months ago. Computed tomography revealed an extensive osteolytic lesion in the right maxillary sinus extending into the orbit and nasal cavity and crossing the midline. Microscopy revealed large necrotic areas admixed by sheets of small, round cells with hyperchromatic nuclei exhibiting a '"salt and pepper" chromatin pattern, which showed immunopositivity for pan-KRT AE1/AE3, EMA, CD56, CD99 (weak), CD138, S100 (focal), vimentin (focal), synaptophysin, FLI1, INSM1, MCPyV, SATB2, and Ki-67 (MKI67 [40%]). Moreover, intact RB1 and wild-type p53 expression were observed. Relevantly, KRT20, KRT5/6, chromogranin A, p40, p63, HMB45, NF, TTF1, TDT (DNTT), PAX5, p16, KIT, as well as high-risk HPV and EBER1/2 (both by ISH), were negative. This report illustrates that a detailed immunohistochemical study, including STAB2 and MCPyV markers, as well as a careful clinical workup, are essential to adequately classify high-grade neuroendocrine carcinomas, especially KRT20-negative MCC.

P16INK4a / Ki67 dual staining immunocytochemistry to refer women infected by HR-HPV for colposcopy.

Cervical cancer is still a significant global health issue, espacially in low- and middle-income countries. Human papillomavirus (HPV) infection is known to be the primary etiological factor in the development of cervical cancer. The identification of high-risk HPV infections in cervical screening is becoming crucial for early detection and management of cervical pre-neoplasia. However, HPV testing requires triage markers since HR HPV infections are widespread in the target population, of which only a small fraction requires detailed clinical work-up by colposcopy. p16INK4a is a tumor suppressor protein that has emerged as a promising surrogate marker for HPV infection. In combination with a proliferation marker Ki67 in one diagnostic test kit referred to as CINtecPlus®- or dual stain (DS) it revealed excellent sensitivity and specificity profiles to detect clinically relevant CIN2+ lesions among HPV-infected women in large screening cohorts. This review examines the role of the cytology CINtecPlus®-test (Dual Stain (DS)-test) as a triage marker to identify patients with CIN2+ lesions among HPV + tested women and summarizes the most recent recommendations for its clinical use.

Clinical utility of plasma p-tau217 in identifying abnormal brain amyloid burden in an Asian cohort with high prevalence of concomitant cerebrovascular disease.

Using an Asian cohort with high prevalence of concomitant cerebrovascular disease (CeVD), we evaluated the performance of a plasma immunoassay for tau phosphorylated at threonine 217 (p-tau217) in detecting amyloid beta positivity (Aβ+) on positron emission tomography and cognitive decline, based on a three-range reference, which stratified patients into low-, intermediate-, and high-risk groups for Aβ+. Brain amyloid status (Aβ- [n=142] vs Aβ+ [n=73]) on amyloid PET scans was assessed along with the plasma ALZpath p-tau217 assay to derive three-range reference points for PET Aβ+ based on 90% sensitivity (lower threshold) and 90% specificity (upper threshold). Plasma p-tau217 (area under the curve [AUC]=0.923) outperformed routine clinical assessments (AUC=0.760-0.819; p ≤ 0.003) and other plasma biomarkers (AUC=0.817-0.834; p < 0.001). The high-risk group showed significantly higher rates of cognitive decline than the low-risk group. Risk stratification for PET Aβ+ based on a plasma p-tau217 assay demonstrated potential diagnostic and prognostic utility in an Asian cohort with concomitant CeVD. The utility of plasma p-tau217 to detect brain amyloid beta pathology (Aβ+) was studied in an Asian cohort with concomitant cerebrovascular disease Plasma tau phosphorylated at threonine 217 (p-tau217) showed superior utility in detecting Aβ+ compared to neuroimaging measures, clinical workup, or other blood biomarkers including p-tau181, glial fibrillary protein (GFAP), and Aβ Higher plasma p-tau217 correlated with faster cognitive decline Plasma p-tau217 shows promise as an Alzheimer's disease (AD) diagnostic and prognostic biomarker in diverse populations.

A Prospective Trial of Biomarker-Guided Surveillance for HPV-Positive Oropharynx Cancer Using Plasma Tumor Tissue–Modified Viral HPV DNA

Abstract Purpose: Observational studies suggest circulating tumor human papillomavirus (HPV) DNA may facilitate early detection of recurrent HPV-positive oropharynx cancer. We prospectively investigated whether biomarker-guided surveillance detects recurrence earlier than the standard-of-care methods. Patients and Methods: We enrolled patients evaluated for HPV-positive oropharynx cancer at a single center from November, 2020, to April, 2023, undergoing curative-intent treatment in a single-arm cohort study. Pretreatment plasma and/or tumor tissue were tested for tumor tissue–modified viral (TTMV) HPV DNA from HPV subtypes 16/18/31/33/35 using a droplet digital PCR–based commercial assay. Posttreatment plasma TTMV was assessed periodically. Detectable/indeterminate tests prompted imaging. The primary outcome was the proportion of recurrences first detected by TTMV. Results: Median follow-up was 23 months, with median six posttreatment TTMV tests for 155 subjects. Fifteen subjects (9%) experienced recurrence. Among these, six [40%, 95% confidence interval (CI) = 16%–68%] were “early true-positives,” for whom TTMV detection predated and prompted the imaging and clinical workup that diagnosed recurrence (median lead time = 132 days; range = 47–280). Another five subjects (33%) were “confirmatory true-positives,” for whom detectable TTMV confirmed suspicious standard-of-care imaging findings. Finally, four subjects (27%) with recurrence had undetectable TTMV at diagnosis (“false-negatives”). False-negatives had low or undetectable pretreatment TTMV, and 2/4 had non-HPV16 genotypes. Finally, three subjects had prolonged detectable TTMV without disease (“false-positives”); all had immunologic comorbidities. Overall, the sensitivity of TTMV for recurrence was 73% (95% CI = 45%–92%). Among 117 subjects with HPV16 and detectable pretreatment TTMV, sensitivity was higher (91%, 95% CI = 59%–100%). Conclusions: TTMV-guided surveillance facilitates early detection of many HPV-positive oropharynx cancer recurrences, with the highest sensitivity for HPV16 and detectable pretreatment TTMV. Clinical implementation should be carefully informed by the limitations described in this study.

Double trouble: a comprehensive study into unrelated genetic comorbidities in adult patients with Facioscapulohumeral Muscular Dystrophy Type I.

Facioscapulohumeral dystrophy type 1 (FSHD1) displays prominent intra- and interfamilial variability, which complicates the phenotype-genotype correlation. In this retrospective study, we investigated FSHD1 patients classified as category D according to the Comprehensive Clinical Evaluation Form (CCEF), a category defined by FSHD patients showing uncommon clinical features, to identify genetic causes explaining these uncommon phenotypes. Demographics, clinical data and clinical scales of FSHD1 patients were retrospectively evaluated. Patients were divided into four CCEF categories, and comparisons between groups were performed. In category D, when uncommon features suggested the presence of an unrelated genetic disease, a more extensive collection of data was performed. 157 FSHD1 patients were included in the study (82 males, 75 females) with mean age of 52.1 ± 13.5 years at the time of the study. D4Z4 repeat sizes ranged between 2 and 10 RU. According to the CCEF, 114 patients were classified into category A, 8 into category B and C each, and 27 into category D. In category D, 9 patients presented uncommon features related to commonly acquired comorbidities, whereas in the remaining 18 patients, all but two with upper-sized FSHD1 D4Z4 repeats (7-10 RU), we suspected an unrelated genetic neurological disease based on clinical phenotype. In 14/18 patients, we identified FSHD-unrelated genetic causes, most often unrelated repeat expansion disorders. This emphasizes the need of careful clinical and genetic work-up to avoid confusion between FSHD-intrinsic clinical variability and clinical features unrelated to the disease.

Application of RNA-Based Next-Generation Sequencing Fusion Assay for Hematological Malignancies.

Recurrent fusions drive the pathogenesis of many hematological malignancies. Compared to routine cytogenetic/fluorescence in situ hybridization (FISH) studies, the RNA-based next-generation sequencing (NGS) fusion assay enables the identification of both known and novel fusions. In many cases, these recurrent fusions are crucial for diagnosis and are associated with prognosis, relapse prediction, and therapeutic options. The aim of this study is to investigate the application of the RNA-based NGS fusion assay in hematological malignancies. Our study included 3101 cases with available fusion results, and a fusion event was identified in 17.6% of cases. The discordant rate between the RNA-based NGS fusion assay and cytogenetic/FISH studies was 36.3%. Further analysis of discordant cases indicated that, compared to cytogenetic/FISH studies, the RNA-based NGS fusion assay significantly improved the identification of cryptic fusion genes, such as NUP98::NSD1, P2RY8::CRLF2, and KMT2A fusions involving different partners. Additionally, our study identified 24 novel fusions and 16 cases with the simultaneous presence of two fusions. These additional findings from the RNA-based NGS fusion assay resulted in improved risk stratification, disease targeting and monitoring. In conclusion, our study demonstrates the feasibility and utility of an RNA-based NGS fusion assay for patients with hematological malignancies, suggesting that it may be essential for the routine clinical workup of these patients.

Use of Magnetic Resonance Neurography for Sensory Nerve Injuries of the Head and Neck.

Identification of peripheral nerve injuries of the head and neck can be challenging due to a broad spectrum of symptoms from neuropathic pain to headaches and migraine. This article aimed to present the clinical features and diagnostic workup of patients with acute and chronic peripheral nerve injuries of the head and neck using magnetic resonance neurography (MRN), to demonstrate potential advantages compared with conventional magnetic resonance imaging (MRI). Patients who presented with suspected peripheral nerve injury were either referred for a conventional MRI or MRN. Patients who underwent nerve exploration for suspected nerve transection and/or neuroma formation on imaging were included in this study. Imaging findings were correlated with intraoperative observations. Four patients (3 women, 1 man, age range: 34-70 years) were included. Three subjects had a history of head and neck surgery and 1 experienced direct trauma to the medial eyebrow. Clinical symptoms included numbness, allodynia, positive Tinel sign, and pain relief following nerve blocks. Two patients underwent conventional MRI and 2 underwent MRN. MRI provided a vague indication of potential neuromas and failed to accurately depict their locations. MRN offered a comprehensive visualization of the entire nerve path, identifying nerve transection and neuromas, as well as precise location, dimensions, and relation to adjacent bones and muscles. High-resolution 3-dimensional MRN provides clear visualization of acute and chronic peripheral nerve injuries of the head and neck region, facilitating early diagnosis of nerve injuries in this region and improving diagnostic accuracy, as well as surgical planning and execution.

Diagnostic clues in herpes encephalitis following radiation therapy.

Herpes encephalitis is known to affect patients undergoing brain radiotherapy, but early diagnosis and treatment, the foremost determinants of disease outcome, remain challenging in this patient population. This can be due to attribution of symptoms to the brain tumor and radiation side effects, as well as patients' atypical clinical presentation. Here we sought to highlight pearls and pitfalls in the clinical course and diagnostic workup which may facilitate timely diagnosis and improve disease outcome. Six patients with post radiation herpes encephalitis were identified in a retrospective review of Hadassah Medical Center medical records of between 2007 and 2022. Their clinical course, brain imaging, labs and EEG findings were included in the study. All six patients presented with fever and a confusional state and four had seizures. Lumbar puncture showed mild CSF pleocytosis in two of five patients, and PCR was positive for HSV1 in four out of five. MRI showed typical findings in all patients, though they were misinterpreted in two of six as disease exacerbation. EEG showed non convulsive status epilepticus in three patients. Outcome was favorable in half of patients. In patients undergoing radiotherapy to the brain and neck, fever and confusional state accompanied by new onset seizures, seizure exacerbation, changes in seizure lateralization and status epilepticus should lead one to consider a diagnosis of herpes encephalitis. A high index of suspicion, a timely workup and empiric treatment in this patient population can alter disease outcome.

STREM2 in discordant CSF Aβ42 and p-tau181.

Little is known about the factors underpinning discordant cerebrospinal fluid (CSF) amyloid beta (Aβ)42 versus p-tau181/Aβ42 or CSF Aβ42 versus Aβ positron emission tomography (PET). We stratified 570 non-demented Alzheimer's Disease Neuroimaging Initiative (ADNI) participants by Aβ PET and further by CSF Aβ42 or p-tau181/Aβ42. We used analysis of covariance testing adjusting for covariates, followed by Tukey post hoc pairwise comparisons, to compare CSF soluble triggering receptor expressed on myeloid cells-2 (sTREM2) across four participant groups: CSF+ Aβ42 with CSF- p-tau/Aβ42, CSF- Aβ42 with CSF+ p-tau/Aβ42, and concordant CSFAβ42/CSFp-tau/Aβ42. We also compared sTREM2 across discordant and concordant CSFAβ42/PET. Regardless of Aβ PET status, CSF+Aβ42 with CSF-p-tau/Aβ42 had lower sTREM2 than CSF-Aβ42 with CSF+p-tau/Aβ42. CSF sTREM2 was similarly also associated with discordant CSF Aβ42 /PET. Our study suggests the potential roles of sTREM2 in discordant CSF Aβ42 and p-tau181/Aβ42 and discordant CSFAβ42/PET. Low- and high-CSF sTREM2 may affect the accuracy of p-tau181/Aβ42 during the clinical work-up of AD. 17% of non-demented older adults had discordant CSF Aβ42 versus p-tau181/Aβ42.sTREM2 differed between discordant cases of CSF Aβ42 versus p-tau181/Aβ42.20% of non-demented older adults had discordant CSF Aβ42 versus Aβ PET.sTREM2 also differed between discordant cases of CSF Aβ42 versus Aβ PET.p-tau181/Aβ42 may miss 6.7% of PET+ non-demented older adults with low sTREM2.

Diagnostic and prognostic potential of left atrial strain in cardiovascular disease: a narrative review.

Left atrial strain (LAS) was recently introduced as a parameter that reflects on left atrial function. Consequently, changes in LAS can inform the development of cardiovascular diseases, hence providing a window for non-invasive and cost-effective testing of these diseases and their complications at early stages of development, potentially offering a segway towards preventive interventions. LAS has yet to be implemented into standard practice. Therefore, we aimed to synthesize the current evidence on the diagnostic and prognostic potentials of LAS in a variety of cardiovascular diseases. We attempted to elucidate sufficient evidence to support uptake into clinical practice. A systematic search of four databases (Medline, PubMed, Embase, CINAHL) was performed for articles published within the last 5 years, for inclusion in this narrative review. A total of 3921 articles were identified, among which only 43 articles were included. LAS showed diagnostic potential in detecting (1) paroxysmal atrial fibrillation in stroke patients, (2) left atrial appendage dysfunction in patients with nonvalvular atrial fibrillation and heart failure with reduced ejection fraction, and finally (3) diastolic dysfunction in patients with arrhythmias, valvulopathies, acute coronary syndrome, primary arterial hypertension, and heart failure. LAS was also prognostic for the development of (1) atrial fibrillation in hypertensive patients, cardiovascular events in patients with (2) valvular diseases and (3) ischemic heart diseases, and (4) heart failure in patients with and without diastolic dysfunction. This review highlights the potential of LAS in identifying certain cardiac pathologies and their repercussions on patient prognosis, which should prompt courageous integration into the clinical workup while emphasizing areas for future research to guarantee successful and safe implementation into clinical practice.

Optimizing Ewing Sarcoma and Osteosarcoma Biopsy Acquisition: A Children's Oncology Group Bone Tumor Committee Consensus Statement.

Trends in diagnostic biopsy sample collection approaches for primary bone sarcomas have shifted in the past 2 decades. Although open/incisional biopsies used to be the predominant approach to obtain diagnostic material for Ewing sarcoma and osteosarcoma, image-guided core needle biopsies have increased in frequency and are safe for patients. These procedures are less invasive and reduce recovery times but have potential limitations. The quantity and quality of tissue obtained through these procedures vary between institutions. Acquired viable tissue volumes can be low, limiting the conduct of downstream expanded clinical workup, molecular analyses, and research. Patients with advanced Ewing sarcoma and osteosarcoma continue to have overall poor outcomes despite dose-intensive cytotoxic chemotherapy. The biology of treatment resistance is not currently well understood, partly due to limited availability of relevant tissue to study. There is a need for access to quality tumor specimens for molecular and other analyses to identify high-risk tumor subsets and drive discovery to improve patient outcomes. Given broad variability in bone tumor tissue procurement and processing across member institutions, the Children's Oncology Group Bone Tumor Committee convened a multidisciplinary group of experts to outline the current and near-future tissue needs for optimal clinical care and access to research platforms. The goal of this working group was to provide high-level guidance on biopsy practices that safely meet these evolving needs. Harmonizing tissue collection practices is paramount to improving the care of children, adolescents, and young adults diagnosed with Ewing sarcoma and osteosarcoma.

Outcomes following laparoscopic adrenalectomy: Experience of more than two decades at a tertiary care centre.

Laparoscopic transperitoneal adrenalectomy was first described by Gagner M et al . Here, we present our experience of more than two decades of laparoscopic adrenalectomy performed in a single surgical unit at a tertiary care centre. A prospectively collected database of patients undergoing laparoscopic adrenalectomy from December 1994 to May 2020 was analysed retrospectively. The demographic profile, details of clinical workup and laboratory parameters were recorded in a pre-structured pro forma. Functional workup and anatomical imaging were performed for all the patients. Patients were taken up for surgery after adequate pre-operative optimisation using a multidisciplinary approach. All the patients were operated by a single surgical team of experienced laparoscopic surgeons. A total of 158 patients underwent laparoscopic transperitoneal adrenalectomy. The majority patients were females (64.5%). The median tumour size was 5 cm (range, 1-18 cm). The diagnosis in the majority of the patients was pheochromocytoma (56.3%). The mean operative time was 80 min (range: 45-210 min). The most common complication was bleeding in 6 (3.7%) patients, which required laparotomy. The median duration of post-operative hospital stay was 3 days (range: 1-13). There was no 30-day mortality. The mean follow-up period was 15 months (range: 6-72 months), during which two patients developed local recurrence. The advantages of laparoscopic surgery are well established and have been extensively explored for the management of adrenal lesions. A multidisciplinary approach to management, consisting of endocrinologists, surgeons and anaesthesiologists is preferred. Pre-operative evaluation, optimisation and accurate selection of patients are crucial for successful laparoscopic adrenalectomy.

Interhospital variations in diagnostic work-up following recall at biennial screening mammography-a population-based study.

Quality control in breast cancer screening programmes has been subject of several studies. However, less is known about the clinical diagnostic work-up in recalled women with a suspicious finding at screening mammography. The current study focuses on interhospital differences in diagnostic work-up strategies. In this retrospective analysis, using a prospectively obtained database, we included 17,809 women who participated in the Dutch national screening programme between 2009 and 2019 and were recalled to a hospital for analysis of a suspicious mammographic abnormality. The diagnostic work-up (e.g., type and frequency of additional imaging and biopsy) in the different hospitals were compared and analysed by multivariable analysis to correct for confounders. Use of biopsy varied from 36.7% to 48.7% (p < 0.001) between hospitals, and the use of problem-solving magnetic resonance imaging (MRI) from 2.1% to 6.9% (p < 0.001). These interhospital differences remained after correction for patients and tumour characteristics. The percentage of women with a delayed breast cancer diagnosis, defined as histopathological confirmation of breast cancer more than three months after recall or first analysis in the hospital, varied from 2.7% to 6.1% between hospitals (p = 0.07). In our screening region interhospital differences were observed in diagnostic work-up following recall at biennial screening mammography. Though statistically significant, absolute differences were small, and therefore, their clinical impact appears to be limited. Question It is unclear how diagnostic work-up strategies vary between hospitals for women recalled after suspicious findings in breast cancer screening. Findings Significant differences in biopsy techniques and the use of problem-solving MRI were observed, though the clinical impact of these variations is likely to be marginal. Clinical relevance Evaluation of interhospital variation in the diagnostic work-up strategies after recall may aid in optimising the quality of breast cancer care and, indirectly, the effectiveness of the screening programme.

State-of-the-Art Narrative Review: Mounier-Kuhn Syndrome and Tracheobronchomegaly.

Mounier-Kuhn syndrome (MKS) or tracheobronchomegaly is an uncommon disease of the central airways. It is characterized by pathological dilatation of the trachea and main bronchi and inevitably leads to recurrent respiratory infections, bronchiectasis, hospitalizations, and results in considerable morbidity and mortality. Despite numerous case reports, there is a shortage of evidence on clinical outcomes and limited data on interventions, thus presenting a significant gap in the literature. Fortunately, new strategies and increasing clinical experience have improved the clinical approach, diagnostic workup, classification, and management of MKS. Articles in English, Spanish, and French were searched from databases, including Pubmed, Google Scholar, Medline, and SCOPUS, using the terms "Mounier-Kuhn syndrome," "Tracheomegaly," "Tracheobronchomegaly," and "Bronchomegaly," without date restrictions. A total of 360 articles with the aforementioned syntax were indexed on Pubmed. This state-of-the-art review attempts to fill a void in the current literature by summarize the current scientific knowledge and highlighting novel interventional strategies in the management of Mounier Kuhn Syndrome.

Endometrial hyperplasia, benign endometrial tumors and endometrial carcinoma: A review study

Background. During the reproductive phase, the endometrium undergoes cyclical structural changes. Endometrial hyperplasia (EH) is a prevalent condition that arises from a combination of estrogen exposure and insufficient progesterone levels. Endometrial cancer (EC) is the second most common gynecologic malignancy, with the likelihood of EH progressing to EC ranging from 1% to 29%. The objective of this study is to conduct a comprehensive assessment of various forms of endometrial hyperplasia, benign endometrial tumors, and endometrial cancer (EC). Methods. A review of published papers from major databases, including PubMed, Scopus, and Google Scholar, was conducted. The search included original research articles and reviews on EH, benign endometrial tumors, and EC. Case reports, series, and clinical images were excluded. Results. Information on the selected topics was summarized, including epidemiology, etiology, histopathological classification, anatomy, biological and molecular characteristics, detection and prevention, clinical manifestations, staging, diagnostic workup, prognostic factors, and management. Conclusion. Endometrial hyperplasia and endometrial cancer are two of the most common problems in women. EH is a major precancerous condition for EC, and EC is associated with a poor prognosis if diagnosed late. The epidemiology and outcomes of both conditions vary according to several factors, including ethnicity, environment, socioeconomic status, heredity, drugs, hormones, and the aging process.

Irreparable subscapularis: Guide for surgeons

The subscapularis (SSC) muscle, one of the four rotator cuff (RC) muscles, plays a crucial role in balancing and moving the shoulder. Cases of irreparable SSC tears are difficult entities within shoulder surgery. Different techniques have been suggested with different outcomes but with no golden standard these days. Musculotendinous transfers, anterior capsular reconstruction (ACR), shoulder arthroplasty and even arthrodesis are the current options available. This article provides a review of existing literature on this entity, covering clinical work-up, operative possibilities, techniques, and rehabilitation.