A novel likely pathogenic CLCN5 variant in Dent's disease.

BACKGROUND: The majority of cases of Dent's disease are caused by pathogenic variants in the CLCN5 gene, which encodes a voltage-gated chloride ion channel (ClC-5), resulting in proximal tubular dysfunction. We present three members of the same family and one unrelated paediatric patient with the same insertion-deletion CLCN5 variant. The identification of these patients and positive familial segregation led to the re-classification of this variant from one of unknown significance to one of likely pathogenicity. CASE PRESENTATION: A 41 year old male presented with end stage kidney failure, proteinuria and haematuria. Whole genome sequencing identified an insertion-deletion variant in CLCN5, resulting in a missense change (c.1744_1745delinsAA p.(Ala582Lys)). His brother and nephew, who both exhibited renal impairment, haematuria, proteinuria, glycosuria and nephrocalcinosis, were found to have the same variant. In addition, genetic testing of an unrelated paediatric patient who presented with proteinuria and hypercalciuria, demonstrated the same variant. CONCLUSIONS: The identification of this novel variant in four individuals with features of Dent's disease, has led to the re-classification of the variant to one of likely pathogenicity. As a result, our patients and any future patients with the same variant can be offered a likely diagnosis, without the need for kidney biopsy, and their family members can be offered genetic screening.

A fast, easy and reliable method for hamstrings graft size prediction in anterior cruciate ligament reconstruction.

PURPOSE: The aim of this study is to describe and validate a simple and reliable method to pre-operatively predict the size of the ACL graft in the double strand technique with autologous semitendinosus-gracilis tendons on the same MRI used for ACL rupture diagnosis. METHODS: The study included 92 patients, with a median age of 31 years (IQR 26-41 years), 73/92 (79%) of whom were males. All patients that underwent an ACL reconstruction with doubled ST + GT between 2017 and 2022 were counted in the study. RESULTS: Overall, the median predicted graft diameter from MR imaging was similar to the actual graft diameter with no significant differences (n.s.). Regarding the comparison between predicted and actual graft size, concordance was 78/92 (85%, 95% CI 76-91%), with κ = 0.797 which corresponds to a level of agreement defined as "Strong". Tendon sizes calculated on pre-operative MRI were evaluated both with intra-observer and inter-observer reliability demonstrating a statistically reproducible method. The predicted graft was then compared to the reported one with a statistically significant reliability found. CONCLUSION: This study can help the surgeons to perform a fast pre-operative planning of an ACL reconstruction for graft selection. If the planned graft with ST and GT is smaller than 8 mm, the clinician can decide to switch to a different type of graft or plan a different graft preparing technique and, therefore, reduce the risk of post-operative ligament re-rupture. The method proposed is reliable and reproducible. The major strength of the planning technique proposed is that it relies on data that are already available for the clinician before surgery, without the need of further analysis. LEVEL OF EVIDENCE: IV.

Technological Convergence: Highlighting the Power of CRISPR Single-Cell Perturbation Toolkit for Functional Interrogation of Enhancers.

Higher eukaryotic enhancers, as a major class of regulatory elements, play a crucial role in the regulation of gene expression. Over the last decade, the development of sequencing technologies has flooded researchers with transcriptome-phenotype data alongside emerging candidate regulatory elements. Since most methods can only provide hints about enhancer function, there have been attempts to develop experimental and computational approaches that can bridge the gap in the causal relationship between regulatory regions and phenotypes. The coupling of two state-of-the-art technologies, also referred to as crisprQTL, has emerged as a promising high-throughput toolkit for addressing this question. This review provides an overview of the importance of studying enhancers, the core molecular foundation of crisprQTL, and recent studies utilizing crisprQTL to interrogate enhancer-phenotype correlations. Additionally, we discuss computational methods currently employed for crisprQTL data analysis. We conclude by pointing out common challenges, making recommendations, and looking at future prospects, with the aim of providing researchers with an overview of crisprQTL as an important toolkit for studying enhancers.

Real-world experience of monoclonal antibodies in mild-to-moderate COVID-19 patients at a tertiary care center.

Background: Neutralizing antibodies cocktail (casirivimab and imdevimab) has received emergency use authorization recommendation by Food and Drug Administration (FDA) and WHO for mild-to-moderate COVID-19 infection in specific high-risk groups. Antibodies cocktail has shown promising results in preventing progression to severe disease, but the real-world experience is still evolving. Herein, we present a retrospective analysis of 22 patients who were administered the antibodies cocktail between August 2021 and March 2022 at our tertiary care center. Methods: We conducted an observational retrospective analysis of clinicoradiological, inflammatory parameters, progression of the disease, and outcome among 22 mild and moderate COVID-19 patients treated with antibodies cocktail. Results: The mean age was 67.7 years (SD ± 18.3) and comprised of 13 males (59%), while 9 were females (40.9%). Nine (40.9%) patients were fully vaccinated with two doses, nine (40.9%) were partially vaccinated with one dose while four patients (18.2%) were unvaccinated, and the rest were unvaccinated. Diabetes and hypertension were the commonest comorbidities; hematological and solid organ malignancies were other comorbidities. Eight patients had radiological opacities consistent with COVID-19 pneumonia and had shown significant regression in four patients after the therapy. None of our patients required supplemental oxygen or progressed to severe acute respiratory distress syndrome. All patients were discharged in a stable condition within 6 days of the therapy. Conclusions: The neutralizing antibodies cocktail has shown encouraging results in our analysis in preventing progression to severe disease in patients with high-risk conditions.

A rare case of primary retroperitoneal extraovarian granulosa cell tumor.

Extraovarian granulosa cell tumors (GCTs) are rare neoplasms. They arise from the ectopic gonadal tissue along the embryonal route of genital ridge. We present a case of an extraovarian tumor in an elderly female who presented with lump in the abdomen occupying the pelvic region. She was operated and the mass was excised with intact capsule. Histopathology revealed the mass to be an adult granulosa cell tumor. Extraovarian granulosa cell tumors are very rare with only 13 such cases reported in literature to date. The present case is the largest primary retroperitoneal adult granulosa cell tumor reported till date.

Adjuvant Radiotherapy in Stage II Endometrial Cancer: Selective De-intensification of Adjuvant Treatment.

AIMS: Risk stratification, including nodal assessment, allows for selective de-intensification of adjuvant radiotherapy in stage II endometrial cancer. Patterns of treatment and clinical outcomes, including the use of reduced volume 'mini-pelvis' radiotherapy fields, were evaluated in a population-based study. MATERIALS AND METHODS: All patients diagnosed with pathological stage II endometrial cancer between 2000 and 2014, and received adjuvant radiotherapy in a regional healthcare jurisdiction were reviewed. Registry data were supplemented by a comprehensive review of patient demographics, disease characteristics and treatment details. The Charlson Comorbidity Score was calculated. Survival and recurrence data were analysed. RESULTS: In total, 264 patients met the inclusion criteria. Most patients had endometrioid histology (83%); 41% of patients had International Federation of Gynecologists and Obstetricians grade 1 disease. Half (49%) had surgical nodal evaluation; 11% received chemotherapy. Most patients (59%) were treated with full pelvic radiotherapy fields ± brachytherapy. Seventeen per cent of patients received mini-pelvis radiotherapy ± brachytherapy, whereas 24% received brachytherapy alone. Five-year recurrence-free survival was 87% for the entire cohort, with no significant difference by adjuvant radiotherapy approach. Only one patient receiving mini-pelvis radiotherapy ± brachytherapy recurred in the pelvis but outside of the mini-pelvis field. Recorded late toxicity rates were highest for full pelvis radiotherapy + brachytherapy. CONCLUSION: Risk stratification in a real-world setting allowed for selective de-intensification of adjuvant radiation with equivalent outcomes for stage II endometrial cancer. Mini-pelvis radiotherapy combined with brachytherapy is effective in highly selected patients, with the potential to decrease toxicity without compromising local control. Brachytherapy should be considered in low-risk stage II patients.

A preoperative prediction model for anastomotic leakage after rectal cancer resection based on 13.175 patients.

INTRODUCTION: This study aims to develop a robust preoperative prediction model for anastomotic leakage (AL) after surgical resection for rectal cancer, based on established risk factors and with the power of a large prospective nation-wide population-based study cohort. MATERIALS AND METHODS: A development cohort was formed by using the DCRA (Dutch ColoRectal Audit), a mandatory population-based repository of all patients who undergo colorectal cancer resection in the Netherlands. Patients aged 18 years or older were included who underwent surgical resection for rectal cancer with primary anastomosis (with or without deviating ileostomy) between 2011 and 2019. Anastomotic leakage was defined as clinically relevant leakage requiring reintervention. Multivariable logistic regression was used to build a prediction model and cross-validation was used to validate the model. RESULTS: A total of 13.175 patients were included for analysis. AL was diagnosed in 1319 patients (10%). A deviating stoma was constructed in 6853 patients (52%). The following variables were identified as significant risk factors and included in the prediction model: gender, age, BMI, ASA classification, neo-adjuvant (chemo)radiotherapy, cT stage, distance of the tumor from anal verge, and deviating ileostomy. The model had a concordance-index of 0.664, which remained 0.658 after cross-validation. In addition, a nomogram was developed. CONCLUSION: The present study generated a discriminative prediction model based on preoperatively available variables. The proposed score can be used for patient counselling and risk-stratification before undergoing rectal resection for cancer.

Single-cell transcriptome maps of myeloid blood cell lineages in Drosophila.

The Drosophila lymph gland, the larval hematopoietic organ comprised of prohemocytes and mature hemocytes, has been a valuable model for understanding mechanisms underlying hematopoiesis and immunity. Three types of mature hemocytes have been characterized in the lymph gland: plasmatocytes, lamellocytes, and crystal cells, which are analogous to vertebrate myeloid cells, yet molecular underpinnings of the lymph gland hemocytes have been less investigated. Here, we use single-cell RNA sequencing to comprehensively analyze heterogeneity of developing hemocytes in the lymph gland, and discover previously undescribed hemocyte types including adipohemocytes, stem-like prohemocytes, and intermediate prohemocytes. Additionally, we identify the developmental trajectory of hemocytes during normal development as well as the emergence of the lamellocyte lineage following active cellular immunity caused by wasp infestation. Finally, we establish similarities and differences between embryonically derived- and larval lymph gland hemocytes. Altogether, our study provides detailed insights into the hemocyte development and cellular immune responses at single-cell resolution.

The effect of vitamin D supplementation on cardiorespiratory fitness and muscle strength in male adults undergoing basic military training.

BACKGROUND: Vitamin D deficiency (VDD) is ubiquitous in the Indian subcontinent. VDD has been shown to impair muscle functions. However, the association of VDD with cardiorespiratory endurance is uncertain. Hence, we enrolled and supplemented vitamin D in military recruits with VDD with an aim to evaluate effect of supplementation on cardiorespiratory endurance and muscle strength. METHOD: We enrolled 90 military recruits with VDD and randomly allotted them to two groups equally. The group I received cholecalciferol granules 60,000 IU every fortnight for twelve weeks (cases), and the group II was observed as control. Muscle strength and cardiorespiratory endurance was assessed with a battery of tests (standing broad jump, bent arm hang test, 20 m shuttle run) at baseline and repeated at the end of training (nineteen weeks). Blood samples were collected for measurement of serum 25(OH)D and parathyroid hormone. RESULTS: In Group I and Group II, there was significant increase in 25(OH) D levels (25.8 ± 7.1 and 17.3 ± 3.5 ng/ml, respectively), and in VO2 max (9.8 ± 8.8 and 12.7 ± 8.6 ml/kg/min, respectively) compared with the baseline values. However, no significant change was observed in muscle strength after supplementation. There was no difference between the groups in VO2 max and muscle strength at baseline and at the end of training. CONCLUSION: Vitamin D supplementation did not improve muscle strength and cardiorespiratory endurance in military recruits with VDD. A significant rise in 25(OH) D was observed even in those not supplemented with vitamin D.

A multicentre cohort study of serum and peritoneal biomarkers to predict anastomotic leakage after rectal cancer resection.

AIM: Anastomotic leakage (AL) is one of the most feared complications after rectal resection. This study aimed to assess a combination of biomarkers for early detection of AL after rectal cancer resection. METHOD: This study was an international multicentre prospective cohort study. All patients received a pelvic drain after rectal cancer resection. On the first three postoperative days drain fluid was collected daily and C-reactive protein (CRP) was measured. Matrix metalloproteinase-2 (MMP2), MMP9, glucose, lactate, interleukin 1-beta (IL1ß), IL6, IL10, tumour necrosis factor alpha (TNFα), Escherichia coli, Enterococcus faecalis, lipopolysaccharide-binding protein and amylase were measured in the drain fluid. Prediction models for AL were built for each postoperative day using multivariate penalized logistic regression. Model performance was estimated by the c-index for discrimination. The model with the best performance was visualized with a nomogram and calibration was plotted. RESULTS: A total of 292 patients were analysed; 38 (13.0%) patients suffered from AL, with a median interval to diagnosis of 6.0 (interquartile ratio 4.0-14.8) days. AL occurred less often after partial than after total mesorectal excision (4.9% vs 15.2%, P = 0.035). Of all patients with AL, 26 (68.4%) required reoperation. AL was more often treated by reoperation in patients without a diverting ileostomy (18/20 vs 8/18, P = 0.03). The prediction model for postoperative day 1 included MMP9, TNFα, diverting ileostomy and surgical technique (c-index = 0.71). The prediction model for postoperative day 2 only included CRP (c-index = 0.69). The prediction model for postoperative day 3 included CRP and MMP9 and obtained the best model performance (c-index = 0.78). CONCLUSION: The combination of serum CRP and peritoneal MMP9 may be useful for earlier prediction of AL after rectal cancer resection. In clinical practice, this combination of biomarkers should be interpreted in the clinical context as with any other diagnostic tool.

Transanal total mesorectal excision: how are we doing so far?

AIM: This subgroup analysis of a prospective multicentre cohort study aims to compare postoperative morbidity between transanal total mesorectal excision (TaTME) and laparoscopic total mesorectal excision (LaTME). METHOD: The study was designed as a subgroup analysis of a prospective multicentre cohort study. Patients undergoing TaTME or LaTME for rectal cancer were selected. All patients were followed up until the first visit to the outpatient clinic after hospital discharge. Postoperative complications were classified according to the Clavien-Dindo classification and the comprehensive complication index (CCI). Propensity score matching was performed. RESULTS: In total, 220 patients were selected from the overall prospective multicentre cohort study. After propensity score matching, 48 patients from each group were compared. The median tumour height for TaTME was 10.0 cm (6.0-10.8) and for LaTME was 9.5 cm (7.0-12.0) (P = 0.459). The duration of surgery and anaesthesia were both significantly longer for TaTME (221 vs 180 min, P < 0.001, and 264 vs 217 min, P < 0.001). TaTME was not converted to laparotomy whilst surgery in five patients undergoing LaTME was converted to laparotomy (0.0% vs 10.4%, P = 0.056). No statistically significant differences were observed for Clavien-Dindo classification, CCI, readmissions, reoperations and mortality. CONCLUSION: The study showed that TaTME is a safe and feasible approach for rectal cancer resection. This new technique obtained similar postoperative morbidity to LaTME.

Multicentre study of non-surgical management of diverticulitis with abscess formation.

This multicentre retrospective cohort study included 447 patients with Hinchey Ib and II diverticular abscesses, who were treated with antibiotics, with or without percutaneous drainage. Abscesses of 3 and 5 cm in size were at higher risk of short-term treatment failure and emergency surgery respectively. Initial non-surgical treatment of Hinchey Ib and II diverticular abscesses was comparable between patients treated with antibiotics only and those who underwent percutaneous drainage in combination with antibiotics, with regard to short- and long-term outcomes. Most do not need drainage.

Incidence, risk factors and prevention of stoma site incisional hernias: a systematic review and meta-analysis.

AIM: Stoma reversal might lead to a stoma site incisional hernia. Recently, prophylactic mesh reinforcement of the stoma site has gained increased attention, supporting the need for accurate data on the incidence of and risk factors for stoma site incisional hernia and to identify high-risk patients. The aim of this study was to assess incidence, risk factors and prevention of stoma site incisional hernias. METHOD: Embase, MEDLINE, Web of Science, Cochrane and Google Scholar databases were searched. Studies reporting the incidence of stoma site incisional hernia after stoma reversal were included. Study quality was assessed with the Newcastle-Ottawa Scale and Cochrane risk of bias tool. Data on incidence, risk factors and prophylactic mesh reinforcement were extracted. RESULTS: Of 1440 articles found, 33 studies comprising 4679 reversals were included. The overall incidence of incisional hernia was 6.5% [range 0%-38%, median follow-up 27.5 (17.54-36) months]. Eleven studies assessed stoma site incisional hernia as the primary end-point, showing an incidence of 17.7% [range 1.7%-36.1%, median follow-up 28 (15.25-51.70) months]. Body mass index, diabetes and surgery for malignant disease were found to be independent risk factors, as derived from eight studies. Two retrospective comparative cohort studies showed significantly lower rates of stoma site incisional hernia with prophylactic mesh reinforcement compared with nonmesh controls [6.4% vs 36.1% (P = 0.001); 3% vs 19% (P = 0.04)]. CONCLUSION: Stoma site incisional hernia should not be underestimated as a long-term problem. Body mass index, diabetes and malignancy seem to be potential risk factors. Currently, limited data are available on the outcomes of prophylactic mesh reinforcement to prevent stoma site incisional hernia.

Role of activating transcription factor 3 and its interacting proteins under physiological and pathological conditions.

Activating transcription factor 3 (ATF3) is a stress-responsive factor that belongs to the activator protein 1 (AP-1) family of transcription factors. ATF3 expression is stimulated by various factors such as hypoxia, cytokines, and chemotherapeutic and DNA damaging agents. Upon stimulation, ATF3 can form homodimers or heterodimers with other members of the AP-1 family to repress or activate transcription. Under physiological conditions, ATF3 expression is transient and plays a pivotal role in controlling the expression of cell-cycle regulators and tumor suppressor, DNA repair, and apoptosis genes. However, under pathological conditions such as those during breast cancer, a sustained and prolonged expression of ATF3 has been observed. In this review, the structure and function of ATF3, its posttranslational modifications (PTM), and its interacting proteins are discussed with a special emphasis on breast cancer metastasis.

Sustained release of chrysin from chitosan-based scaffolds promotes mesenchymal stem cell proliferation and osteoblast differentiation.

Numerous phytochemical compounds have recently been reported to stimulate osteogenesis. In this study, the bioavailability and osteogenic effects of chrysin, a natural flavonoid, were investigated. Chrysin was incorporated at different concentrations into biocomposite scaffolds containing carboxymethyl cellulose, chitosan, and nano-hydroxyapatite, through the freeze-drying method. The physicochemical and material characteristics of chrysin-incorporated scaffolds were investigated, and chrysin had no effect on them. These chrysin-containing scaffolds were not cytotoxic to mouse mesenchymal stem cells (mMSCs). Chrysin released from scaffolds stimulated cell proliferation and promoted osteoblast differentiation. Osteoblast differentiation enhanced by chrysin from scaffolds could be due to downregulation of co-repressors of the osteoblast differentiation transcription factor Runx2 in these cells. Thus, chrysin release from scaffolds has potential effects on proliferation and differentiation of mMSCs; hence, it has potential application in bone tissue engineering.

Systemic Inflammatory Cytokines Predict the Infectious Complications but Not Prolonged Postoperative Ileus after Colorectal Surgery.

AIM: Postoperative ileus (POI) is common after surgery. Animal studies indicate that the POI mechanism involves an inflammatory response, which is also activated during postoperative complications. This study aimed to determine whether inflammatory biomarkers might facilitate an early detection of prolonged POI (PPOI) or infectious complications. METHODS: Forty-seven adult patients who underwent oncological colorectal surgery were included. They filled out a perioperative diary to report their gastrointestinal symptoms. Blood samples were collected preoperatively, and on postoperative day (POD) 1 and 3. Levels of leucocytes, C-reactive protein (CRP), interleukin (IL)-6, TNF-α, and IL-1ß were analyzed. RESULTS: Patients with PPOI had significantly longer stay in hospital than patients without (13.6 ± 10.5 versus 7.4 ± 3.2 days, p < 0.001); they also had higher levels of IL-6 ratios, leucocytes, and CRP levels, but did not reach significance. Higher levels of postoperative IL-6 and CRP levels (p < 0.05, resp.) were found in patients with infectious complications. The receiver operating characteristic (ROC) analysis found better diagnostic values of IL-6 ratio on both POD 1 and 3 than that of CRP (POD 1: ROC 0.825, p < 0.001). CONCLUSION: Blood levels of inflammatory cytokines cannot predict PPOI after colorectal surgery. Instead, postoperative IL-6 changes may predict the infectious complications with a better diagnostic value than the current leukocytes or CRP tests.

Non-operative treatment as a strategy for patients with parastomal hernia: a multicentre, retrospective cohort study.

AIM: Parastomal hernia is the most common complication following stoma construction. Surgical treatment is usually chosen over non-operative treatment, but a clear rationale for the choice of management is often lacking. This study aims to investigate the reasons for non-operative treatment, cross-over rates and postoperative complications. METHOD: A multicentre, retrospective cohort study was conducted. Patients diagnosed with a parastomal hernia between January 2007 and December 2012 were included. Data on baseline characteristics, primary surgery and hernias were collected. For non-operative treatment, reasons for this treatment and cross-over rates were evaluated. For all patients undergoing surgery (surgical treatment and cross-overs), complication and recurrence rates were analysed. RESULTS: Of the 80 patients included, 42 (53%) were in the surgical treatment group and 38 (48%) in the non-operative treatment group. Median follow-up was 46 months (interquartile range 24-72). The reasons for non-operative treatment were absence of symptoms in 12 patients (32%), comorbidities in nine (24%) and patient preference in three (7.9%). In 14 patients (37%) reasons were not documented. Eight patients (21%) crossed over from non-operative treatment to surgical treatment, of whom one needed emergency surgery. In 23 patients (55%), parastomal hernia recurred after the original surgical treatment, of whom 21 (91%) underwent additional repair. CONCLUSION: Parastomal hernia repair is associated with high recurrence and additional repair rates. Non-operative treatment has a relatively low cross-over and emergency surgery rate. Given these data, non-operative treatment might be a better choice for patients without complaints or with comorbidities.

Basic echocardiography for undergraduate students: a comparison of different peer-teaching approaches.

BACKGROUND: The aim of this study was to assess the impact of different teaching interventions in a peer-teaching environment on basic echocardiography skills and to examine the influence of gender on learning outcomes. METHODS: We randomly assigned 79 s year medical students (55 women, 24 men) to one of four groups: peer teaching (PT), peer teaching using Peyton's four-step approach (PPT), team based learning (TBL) and video-based learning (VBL). All groups received theoretical and practical hands-on training according to the different approaches. Using a pre-post-design we assessed differences in theoretical knowledge [multiple choice (MC) exam], practical skills (Objective Structured Practical Examination, OSPE) and evaluation results with respect to gender. RESULTS: There was a significant gain in theoretical knowledge for all students. There were no relevant differences between the four groups regarding the MC exam and OSPE results. The majority of students achieved good or very good results. Acceptance of the peer-teaching concept was moderate and all students preferred medical experts to peer tutors even though the overall rating of the instructors was fairly good. Students in the Video group would have preferred a different training method. There was no significant effect of gender on evaluation results. CONCLUSIONS: Using different peer-teaching concepts proved to be effective in teaching basic echocardiography. Gender does not seem to have an impact on effectiveness of the instructional approach. Qualitative analysis revealed limited acceptance of peer teaching and especially of video-based instruction.

It's time to change perspective! New diagnostic tools for lateral elbow pain.

PURPOSE: The presence of intra-articular findings that may complement the extra-articular pathology in lateral epicondilytis has been suggested, and a role for minor instability of the elbow as part of the causative process of this disease has been postulated. This study was designed to describe two new clinical tests, aimed at detecting intra-articular pathology in patients affected by recalcitrant lateral epicondylitis and investigate their diagnostic performance. METHODS: Ten patients suffering of atraumatic lateral elbow pain unresponsive to conservative treatment were considered in this study. Two clinical tests were developed and administrated prior to arthroscopy: Supination and Antero-Lateral pain Test (SALT); Posterior Elbow Pain by Palpation-Extension of the Radiocapitellar joint (PEPPER). Sensitivity, specificity, predictive values and accuracy of SALT and PEPPER as diagnostic tests for seven intra-articular findings were calculated. RESULTS: In 90% of the patients, at least one test was positive. All patients with signs of lateral ligamentous patholaxity or intra-articular abnormal findings had a positive response to at least one of the two tests. SALT proved to have a high sensitivity but a low specificity and is accurate in detecting the presence of intra-articular abnormal findings, especially synovitis. PEPPER test was sensible, specific and accurate in the detection of radial head chondropathy. CONCLUSIONS: Two new diagnostic tests (SALT and PEPPER) were specifically designed to evoke pain from intra-articular structures. These tests could be a valid support in the diagnostic algorithm of recalcitrant lateral elbow pain. Positive findings may be indicative of a minor instability of the lateral elbow condition. LEVEL OF EVIDENCE: Diagnostic study, development of diagnostic criteria on basis of consecutive patients, level II.