Dysplasia Group Research Articles

Biallelic variants in CCN2 underlie an autosomal recessive kyphomelic dysplasia.

Kyphomelic dysplasia is a rare heterogenous group of skeletal dysplasia, characterized by bowing of the limbs, severely affecting femora with distinct facial features. Despite its first description nearly four decades ago, the precise molecular basis of this condition remained elusive until the recent discovery of de novo variants in the KIF5B-related kyphomelic dysplasia. We ascertained two unrelated consanguineous families with kyphomelic dysplasia. They had six affected offsprings and we performed a detailed clinical evaluation, skeletal survey, and exome sequencing in three probands. All the probands had short stature, cleft palate, and micro-retrognathia. Radiographs revealed kyphomelic femora, bowing of long bones, radial head dislocations and mild platyspondyly. We noted two novel homozygous variants in CCN2 as possible candidates that segregated with the phenotype in the families: a missense variant c.443G>A; p.(Cys148Tyr) in exon 3 and a frameshift variant, c.779_786del; p.(Pro260LeufsTer7) in exon 5. CCN2 is crucial for proliferation and differentiation of chondrocytes. Earlier studies have shown that Ccn2-deficient mice exhibit twisted limbs, short and kinked sterna, broad vertebrae, domed cranial vault, shorter mandibles, and cleft palate. We studied the impact of CCN2 knockout in zebrafish models via CRISPR-Cas9 gene editing. F0 knockouts of ccn2a in zebrafish showed altered body curvature, impaired cartilage formation in craniofacial region and either bent or missing tails. Our observations in humans and zebrafish combined with previously described skeletal phenotype of Ccn2 knock out mice, confirm that biallelic loss of function variants in CCN2 result in an autosomal recessive kyphomelic dysplasia.

Rates of tracheostomy in patients with complex skeletal dysplasia: A 32-year institutional experience

ObjectiveRespiratory failure secondary to multilevel airway compromise may present complex airway challenges in patients with specific skeletal dysplasia diagnoses. This study sought to identify and characterize subgroups of skeletal dysplasia diagnoses that more frequently undergo operative airway evaluations and tracheostomy placement. MethodsRetrospective electronic medical record review of pediatric patients with an ICD-10 associated skeletal dysplasia diagnosis and CPT-specified airway intervention at a tertiary pediatric hospital from 1990 to 2022. Patients without a defined skeletal dysplasia diagnosis, subjects with craniosynostosis syndromes, and those with limited clinical data were excluded. Collected variables included demographics, age at diagnosis, comorbidities, operative procedures, and airway interventions. Descriptive statistical analysis was utilized to evaluate data distribution. ResultsFrom the initial population of 313 patients, 41 subjects were confirmed to have clinical features and/or genetic testing consistent with a skeletal dysplasia diagnosis. A tracheostomy was placed in 19/41 subjects and these patients’ records were further analyzed. Skeletal dysplasia groups with more frequent tracheostomy placement included Filamins and related disorders, Sulfation disorders, and Chondrodysplasia punctata. In the patients with a tracheostomy, skeletal dysplasia was diagnosed at a median age of 0.3 years (IQR 4.8 years), and tracheostomy was initiated at a median age of 1.8 years (IQR 2.2 years). Only four of these patients were successfully decannulated, and two subjects are deceased. ConclusionOver 32 years, nearly half of the skeletal dysplasia patients who underwent airway interventions eventually had a tracheostomy placed. Respiratory insufficiency and complex airway management challenges are common manifestations of skeletal dysplasia.

Identification of a novel BAAT frameshift mutation in a female child diagnosed with skeletal dysplasia: A case report.

Skeletal dysplasias are a complex series of rare genetic disorders that cause irregular development of bones, joints, and cartilages in children. A total of 770 disorders associated with 41 groups of skeletal dysplasia have been documented, demonstrating a wide range of clinical manifestations and varying levels of severity. In addition to conventional methods, whole genome sequencing has emerged as a useful approach to pinpointing the underlying etiology of skeletal dysplasias. A 13-month-old female was admitted to the hospital due to the symptoms of jaundice and failure to thrive. The child was subjected to blood tests and a radiographic assessment. The blood chemistries revealed elevated levels of total bilirubin (178 µmol/L), bile acids (198 µmol/L), and low levels of serum calcium (1.69 mmol/L) and phosphate (0.8 mmol/L), along with irregular skeletal development in the forearms and legs, considering rickets and cholestasis. Whole exome sequencing data of the proband revealed a homozygous mutation of c.388dupA in the BAAT (bile acid-CoA: amino acid N-acyltransferase) gene sequence. This mutation caused a frameshift in the amino acid of the BAAT protein, resulting in the pR130Kfs*12 variant. This mutation has been identified as the underlying cause of skeletal dysplasia in the proband. A novel frameshift mutation in the BAAT gene of a Vietnamese female child diagnosed with skeletal dysplasia has been studied by whole exome sequencing analysis. This research reported a case of skeletal dysplasia caused by a frameshift mutation in the BAAT gene. The results of this study contribute to our understanding of the diverse factors that influence irregular skeletal development in children and provide genetic data to support clinical practice.

Overall and cause-specific mortality among patients diagnosed with gastric precancerous lesions in Sweden between 1979 and 2014: an observational cohort study

BackgroundThe Correa’s cascade, encompassing chronic non-atrophic gastritis, atrophic gastritis, intestinal metaplasia, and dysplasia, represents the well-recognized pathway for the development of non-cardia gastric cancer. Population-based studies on all-cause and cause-specific mortalities among patients with gastric lesions in Correa’s cascade are scarce.MethodsWe compiled a cohort of 340 744 eligible patients who had undergone endoscopy with biopsy for non-malignant indications during the period 1979–2011, which was followed up until 2014. Standardized mortality ratios (SMRs) with 95% confidence intervals (CIs) provided estimation of the relative risk, using the general Swedish population as reference. Cox regression model was used to estimate hazard ratios (HRs) of death for internal comparison.ResultsA total of 306 117 patients were included in the final analysis, accumulating 3,049,009 person-years of follow-up. In total 106,625 deaths were observed during the study period. Compared to the general population, excess risks of overall mortality were noted in all subgroups, with SMRs ranging from 1.11 (95% CI 1.08–1.14) for the normal mucosa group to 1.54 (95% CI 1.46–1.62) for the dysplasia group. For cause-specific mortalities, mortality from gastric cancer gradually increased along Correa’s cascade, with excess risk rising from 105% for patients with chronic gastritis to more than 600% for the dysplasia group. These results were confirmed in the comparison with the normal mucosa group. For non-cancer conditions, increased death risks were noted for various diseases compared to the general population, especially among patients with more severe gastric precancerous lesions. But the results were confirmed only for “infectious diseases and parasitic diseases”, “respiratory system diseases”, and “digestive system disease”, when using the normal mucosa group as reference.ConclusionsIncreased mortality from gastric cancer suggests that early recognition and intervention of gastric precancerous lesions probably benefit the patients. Excess mortality due to non-cancer conditions should be interpreted with caution, and future studies are warranted.

Surgical treatment compared with “wait and see” in patients affected by oral leukoplakia to prevent oral cancer: Preliminary data from a multicenter randomized controlled trial

AbstractObjectiveOral leukoplakia (OL) is one of the most common and investigated oral potentially malignant disorders (OPMD). Preventing OSCC occurrence should be the primary outcome in the clinical management of OL. Surgical removal of OL is performed by most clinicians, although its effectiveness in reducing OSCC onset has still not been established by randomized controlled trials (RCT). Wait and see approach is characterized by frequent clinical examinations and periodical biopsies of OL, avoiding unnecessary surgical procedures.This is the first multicenter RCT in literature aiming at comparing the effectiveness of surgical removal and the “wait and see” approach in preventing OSCC onset in patients affected by dysplastic and non‐dysplastic OL.MethodsTwo Italian referral care centres for oral diseases were involved in this multicenter two‐arm RCT comparing the surgical removal of OL (group A) and the “wait and see” approach (group B), with the aim of reducing oral cancer onset.ResultsThis report shows preliminary data on the first 161 patients, with a mean follow‐up of 19.14 ± 11.25 months. Eight cases of OSCC occurred (6 out 8 involving the tongue): one case in group A and seven cases in group B. Moreover, OL recurred in 13 (20%) cases after surgical excision.ConclusionsWithin the limitations of this preliminary report, these initial data underline the increased risk of OSCC onset in the case of OL of the tongue in the presence of epithelial dysplasia in group B (“wait and see”) compared to group A (surgery). This RCT is currently ongoing at the same clinical departments, with the aim of enrolling 310 patients and collecting data at 5‐year follow‐up, in order to achieve conclusive results, in an evidence‐based medicine approach.

Outcomes after completing growth-friendly surgical treatment for early-onset scoliosis in patients with skeletal dysplasia.

The aim of this study was to compare outcomes after growth-friendly treatment for early-onset scoliosis (EOS) between patients with skeletal dysplasias versus those with other syndromes. We retrospectively identified 20 patients with skeletal dysplasias and 292 with other syndromes (control group) who had completed surgical growth-friendly EOS treatment between 1 January 2000 and 31 December 2018. We compared radiological parameters, complications, and health-related quality of life (HRQoL) at mean follow-up of 8.6 years (SD 3.3) in the dysplasia group and 6.6 years (SD 2.6) in the control group. Mean major curve correction per patient did not differ significantly between the dysplasia group (43%) and the control group (28%; p = 0.087). Mean annual spinal height increase was less in the dysplasia group (9.3 mm (SD 5.1) than in the control group (16 mm (SD 9.2); p < 0.001). Mean annual spinal growth adjusted to patient preoperative standing height during the distraction period was 11% in the dysplasia group and 14% in the control group (p = 0.070). The complication rate was 1.6 times higher (95% confidence interval (CI) 1.3 to 2.0) in the dysplasia group. The following complications were more frequent in the dysplasia group: neurological injury (rate ratio (RR) 5.1 (95% CI 2.3 to 11)), deep surgical site infection (RR 2.2 (95% CI 1.2 to 4.1)), implant-related complications (RR 2.0 (95% CI 1.5 to 2.7)), and unplanned revision (RR 1.8 (95% CI 1.3 to 2.5)). Final fusion did not provide additional spinal height compared with watchful waiting (p = 0.054). There were no significant differences in HRQoL scores between the groups. After growth-friendly EOS treatment, patients with skeletal dysplasias experienced a higher incidence of complications compared to those with other syndromes. Surgical growth-friendly treatment for skeletal dysplasia-associated EOS should be reserved for patients with severe, progressive deformities that are refractory to nonoperative treatment.

Short-term and long-term outcomes of transduodenal ampullectomy for patients with early ampullary cancer.

e16244 Background: Transduodenal ampullectomy (TDA) has been attempted in early ampullary cancer. However, the indication and extent of TDA with curative intent remain controversial. Here, we address the perioperative and long-term outcomes of patients with early ampullary cancer who underwent TDA. Methods: Ten early ampullary cancer patients who underwent TDA and 11 early ampullary cancer patients who underwent subtotal stomach-preserving pancreatoduodenectomy (SSPPD) at this institute were respectively enrolled. Among this cohort, we analyzed the perioperative outcomes and long-term outcomes. Results: In terms of the perioperative outcomes between the TDA and SSPPD groups, the TDA group exhibited a shorter operating time (244 minutes vs. 390 minutes, p = 0.003), less intraoperative blood loss (67.5 grams vs. 774 grams, p = 0.006) and shorter length of postoperative hospital stay (15 days vs. 33 days). With respect to the postoperative nutrition status, the TDA group exhibited less postoperative weight loss (0.67% vs. 8.95%, p = 0.021), a better CONUT score (1.0 vs. 2.1, p = 0.011) and a better PNI score (42.9 vs. 40.9, p = 0.018). The 5-year survival rate in the adenoma with high-grade dysplasia (HGD) and T1a (M) groups was 100%, while the median survival time in the T1a (OD) group was 20.7 months (p = 0.0028). Conclusions: TDA is assumed to be a feasible and effective surgical procedure for the treatment of selected patients with early ampullary cancer, including patients with adenoma with HGD or T1a (M) ampullary cancer.

Increased Active Inflammation in the Colon is Not a Reliable Predictor of an Elevated Risk of Dysplasia in Patients With Primary Sclerosing Cholangitis and Ulcerative Colitis.

Although the increased risk of colorectal neoplasia in patients with both primary sclerosing cholangitis (PSC) and ulcerative colitis (UC; termed PSC-UC) is well documented, the mechanism through which concomitant PSC increases the risk of colorectal neoplasia remains unclear. Given that the risk of colorectal neoplasia in UC is positively correlated with increased histologic inflammation, this study sought to investigate whether increased histologic inflammation could be used to stratify the risk of dysplasia development in patients with PSC-UC. Twenty patients with PSC-UC and dysplasia were compared with 30 control patients with PSC-UC who had no history of neoplasia. For each patient, all surveillance biopsies were scored using a 4-point scoring system: (1) no epithelial neutrophils = 0, (2) cryptitis only = 1, (3) cryptitis plus crypt abscess in <50% of crypts = 2, and (4) crypt abscess in ≥50% of crypts, erosion, neutrophilic exudate, and/or ulceration = 3. A score was designated for each biopsy, and both mean and maximum inflammation scores were calculated from all biopsies taken during each colonoscopy. The inflammation burden score was calculated for each surveillance interval by multiplying the average maximum score between each pair of surveillance episodes by the length of the surveillance interval in years. The average scores derived from all colonoscopies for each patient were used to determine the patient's overall mean, maximum, and inflammation burden scores. In both the dysplasia and control groups, the 3 summative inflammation scores were calculated independently for the entire colon, right colon, and left colon. The dysplasia group consisted of 14 (70%) men and 6 (30%) women, with a mean age of 27 years at UC diagnosis and a long history of pancolitis (mean duration: 17y). A total of 49 dysplastic lesions were detected in the dysplasia group, and 8 (40%) of the 20 patients had multifocal dysplasia. The majority of dysplastic lesions belonged to nonconventional subtypes (n = 28; 57%) and were located in the right colon (n = 37; 76%). Irrespective of the colon segment, there was no significant difference in the 3 summative inflammation scores between the dysplasia and control groups ( P > 0.05). However, in each group, the 3 summative inflammation scores were significantly higher in the right colon than in the left colon ( P < 0.05). In conclusion, patients with PSC-UC exhibit increased histologic inflammation in the right colon compared with the left colon, regardless of the presence of dysplasia. Although this may provide an explanation for the predominance of right-sided colorectal neoplasia in patients with PSC-UC, increased histologic inflammation does not reliably predict an elevated risk of dysplasia in patients with PSC-UC. These findings reinforce the current recommendation for annual endoscopic surveillance for all patients with PSC-UC, irrespective of the extent and severity of inflammation.

Associations between Clinicopathological Characteristics and Intraoperative Opioid Requirements during Endoscopic Submucosal Dissection with Monitored Anesthesia Care: A Retrospective Study.

Background and study aims: Endoscopic submucosal dissection is used to treat early gastric neoplasms. Compared with other endoscopic procedures, it requires higher doses of opioids, leading to adverse events during monitored anesthesia care. We investigated the correlations between clinicopathological characteristics and intraprocedural opioid requirements in patients who underwent endoscopic submucosal dissection under monitored anesthesia care. Patients and methods: The medical records of patients who underwent endoscopic submucosal dissection under monitored anesthesia care were retrospectively reviewed. The dependent variable was the total dose of fentanyl administered during the dissection, while independent variables were patient demographics, the American Society of Anesthesiologists physical status classification, preoperative vital sign data, and the pathological characteristics of the neoplasm. Correlations between variables were examined using multiple regression analysis. Results: The study included 743 patients. The median total fentanyl dose was 100 mcg. Younger age (coefficient -1.37; 95% confidence interval [CI] -1.78 to -0.95), male sex (16.12; 95% CI 6.99-25.24), baseline diastolic blood pressure (0.44; 95% CI 0.04-0.85), neoplasm length (1.63; 95% CI 0.90-2.36), and fibrosis (28.59; 95% CI 17.77-39.42) were positively correlated with the total fentanyl dose. Total fentanyl dose was higher in the differentiated (16.37; 95% CI 6.40-26.35) and undifferentiated cancers group (32.53; 95% CI 16.95-48.11) than in the dysplasia group; no significant differences were observed among the others. The mid-anterior wall (22.69; 95% CI 1.25-44.13), mid-posterior wall (29.65; 95% CI 14.39-44.91), mid-greater curvature (28.77; 95% CI 8.56-48.98), and upper groups (30.06; 95% CI 5.01-55.12) had higher total fentanyl doses than the lower group, whereas doses did not significantly differ for the mid-lesser curvature group. Conclusions: We identified variables that influenced opioid requirements during monitored anesthesia care for endoscopic submucosal dissection. These may help predict the needed opioid doses and identify factors affecting intraprocedural opioid requirements.

Shallow trochlear groove and narrow medial trochlear width at the proximal trochlea in patients with trochlear dysplasia: Athree-dimensional computed tomography analysis.

Although the Dejour classification is the primary classification system for evaluating trochlear dysplasia, concerns have been raised about its reliability owing to its qualitative criteria and challenges associated with obtaining accurate radiographs. This study aimed to quantify trochlear dysplasia using three-dimensional (3D) computed tomography (CT) reconstruction with novel parameters related to the transepicondylar axis (TEA). Sixty patients were enrolled, including 20 with trochlear dysplasia and 40 healthy controls. The 3D CT model was generated using the Materialise Interactive Medical Image Control System software. The following six parameters were measured in eight consecutive planes at 15° intervals (planes 0-105): the distance from the TEA to the most cortical point of the lateral condyle ('LP-TEA', where LP stands for lateral peak), medial condyle ('MP-TEA', MP for medial peak)and deepest point of the trochlea ('TG-TEA', TG for trochlear groove). The distances from the medial epicondyle (MEC) to the corresponding TEA points were measured ('LP-MEC', 'MP-MEC'and 'TG-MEC'). In the dysplasia group, TG-TEA (planes 0, 15and 30) and MP-MEC (planes 0, 15and 30) were significantly greater than those in the control group (all p < 0.05 for planes of TG-TEA and MP-MEC). For type A dysplasia, LP-MEC (plane 0) was greater than that in the control group. For type B dysplasia, the MP-MEC (planes 0 and 15) and TG-TEA (planes 0 and 15) were greater than those of the control group. For type D dysplasia, MP-MEC (planes 0, 15and 30) and TG-TEA (planes 0 and 15) were elevated. The 3D CT reconstruction analysis established a reproducible method for quantifying osseous trochlear morphology. Patients with trochlear dysplasia had a shallow TG and narrow medial trochlear width at tracking angles of 0°-30°. This finding corroborates the clinical manifestations of recurrent patellar instability that occur during early flexion. Level III.

The role of the cartilaginous to osseous acetabular angle ratio in children with developmental dysplasia of the hip.

This study aims to demonstrate the use of the cartilaginous to osseous acetabular angle ratio (AAR) in surgical decision-making for hip dysplasia. Data were collected from patients who underwent an MRI of the hip after conservative treatment for developmental dysplasia of the hip between August 2019 and 2022. The data included demographic information as well as an anteroposterior pelvic radiograph. The osseous acetabular index (OAI) was measured using x-ray, while the cartilaginous acetabular index (CAI) and the cartilaginous acetabulum head index (CAHI) were measured using MRI. The square of the CAI to OAI, AAR, was calculated. The patients in the residual hip dysplasia (RHD) group were categorized as having an OAI above 20°. During the postoperative follow-up, we evaluated the patients in this group who underwent Bernese triple pelvic osteotomy. Data on surgical patients with an observation period that exceeded 1 year were collected and analyzed. The distribution of the AAR among the different groups was analyzed. A receiver operating characteristic (ROC) predictive model was constructed using the AAR of the patients in the normal and surgical groups to evaluate the need for surgery. It was found that there was a significant difference in the OAI, CAI, CAHI, and AAR between the RHD group (OAI 26.15 ± 3.90°, CAI 11.71 ± 4.70°, CAHI 79.75 ± 6.27%, and AAR 5.88 ± 4.24) and the control group patients (OAI 16.77 ± 5.39°, CAI 6.16 ± 3.13°, CAHI 85.05 ± 4.91%, and AAR 2.71 ± 2.08) (p < 0.001). A total of 93.5% of the control group patients had an AAR ≤5, while only 6.5% had an AAR >5. The results of postoperative imaging follow-up were "excellent" in 52 patients and "good" in 3, while the functional follow-up results were excellent in 53 and good in 2. In 15 patients, the observation period exceeded 1 year. The mean observation period was 633.1 ± 259.6 days and the preoperative CAHI was 71.7 ± 4.8%. Of the patients with an AAR >5, a substantial 94.8% (55/58) of them were reported to have undergone surgery, while all patients with an AAR less than or equal to 5 did not undergo surgery (91/91). Based on the ROC, a cutoff value of 5.09 was identified for the need for surgery in children with RHD. A surgical decision for residual hip dysplasia can be based on the AAR. An AAR >5 may be a potential indicator for surgical intervention in patients with RHD.

Differential diagnosis of gastric low- and high grade dysplasia using C6orf15 protein

ObjectiveTo investigate the expression of C6orf15 protein in gastric endoscopic biopsy specimens and its usage as an ancillary diagnostic biomarker in determining the grade of gastric dysplasia. MethodsWe selected 102 patients with gastric endoscopic biopsy specimens from Jinling Hospital. These were divided into four groups: 22 cases of gastric mucosal benign lesions, 28 with low-grade dysplasia (LGD, intestinal-type: 21 cases，foveolar-type: 7cases), 28 with high-grade dysplasia (HGD, intestinal-type: 20 cases，foveolar-type: 8 cases), and 24 cases of gastric adenocarcinoma. We examined the expressions of C6orf15, P53, and Ki67 in 102 gastric endoscopic biopsy specimens, including 47 cases with accompanying endoscopic submucosal dissection (ESD) specimens, using immunohistochemistry. ResultsIn gastric HGD and gastric adenocarcinoma, the c6orf15 protein exhibits diffuse and strong cytoplasmic expression in tumor cells. Conversely, in gastric LGD and benign gastric mucosal lesions, the c6orf15 protein shows negative or faint yellow cytoplasmic staining. The expression rate of C6orf15 in high-grade gastric dysplasia (HGD, 93 %) and gastric adenocarcinoma (100 %) was significantly higher than in the gastric mucosal benign lesion group (0 %) and the low-grade dysplasia (LGD, 7 %) group (P < 0.001). ConclusionThe detection of C6orf15 protein expression could serve as a valuable adjunctive diagnostic tool for distinguishing between gastric HGD, LGD, and benign lesions. The combined assessment of C6orf15, P53, and Ki67 expressions may be beneficial in determining the grade of gastric dysplasia and evaluating the risk of progression in gastric mucosal lesions in clinical practice.

Longer Colonoscopy Withdrawal Time Is Associated With the Detection of Visible Dysplasia in Patients With Inflammatory Bowel Disease.

Colonoscopy withdrawal time (CWT) of at least 6-9 minutes is the minimum time needed for adequate adenoma detection in the general population. The ideal CWT in patients with inflammatory bowel disease (IBD) has not been determined. We aimed to identify the optimal CWT associated with the detection of visible dysplasia in patients with IBD. This is a retrospective study from 1/1/2017 to 9/1/2022 of adult patients with IBD in endoscopic healing undergoing surveillance via high-definition white light colonoscopy. The primary outcome was the association of CWT with visible dysplasia detection. A total of 259 patients (mean age 56 ± 14.8 years; 51.3% female, 68% with ulcerative colitis; 8.9% with primary sclerosing cholangitis) underwent 330 colonoscopies. Patients with visible dysplasia were more likely to be older (P < .001) and have a personal history of visible dysplasia (P < .001) and invisible dysplasia (P = .023). The mean CWT was significantly longer in the visible dysplasia group at 26 minutes (interquartile range [IQR] 20-38.5) vs. 21 minutes (IQR 15-28) in procedures without visible dysplasia (P < .001). On multivariable analysis, increased age (P < .001), increased CWT (P = .001), and personal history of visible dysplasia (P = .013) were independently associated with the detection of visible dysplasia. A CWT of ≥15 minutes (odds ratio [OR] 2.71; 95% confidence interval [CI], 1.11-6.6; P = .02] and not ≥9 minutes (OR 2.57; 95% CI, 0.33-20.2; P = .35) is significantly associated with detection of visible dysplasia. For patients with IBD undergoing surveillance via high-definition white light colonoscopy, the mean CWT was independently associated with the detection of visible dysplasia.

(282) Penile Crural Dysplasia is a New Identified Factor for Erectile Dysfunction

Abstract Introduction Given the penile fibro-vascular assembly was just thoroughly interpreted recently and inspired by impotent patients' questions during daily practice, so does the penile venous stripping (PVS), which is deemed controversial thus far. Despite primary impotence (PI) being ascribed to psychogenic origin, in the large repository of PVS treating PI, some 5 % remain refractory in the last decade, an analysis deemed required. Objective We sought to report penile crural dysplasia or hypoplasia that prevents sustainability compared to most PVS males thus far. Methods A retrospective analysis was conducted internationally on 45 consecutive young men with PI from 2013 to 2023. They were allocated into the crural dysplasia group (CDG, n=8), defined as a 50% diameter difference between the largest penile crus and corresponding corpus cavernosum or a 25% diameter difference of bilateral penile crura, and no crural-dysplasia group (NCG, n=37). On an ambulatory basis under acupuncture-aided local anesthesia, neither electrocautery nor a suction apparatus is used, with a circumferential or semi-circumcision followed by a pubic longitudinal approach, the PVS entailed the erection-related vein, including stripping a deep dorsal vein, two cavernosal veins after each emissary's vein was firmly ligated closest to the outer tunic layer with a 6–0 nylon suture. In contrast, the four para-arterial veins were only segmentally ligated. The overlying fascia layers and skin were approximated with a 6–0 nylon and 5–0 chromic suture for the skin, as did the semi-circumcision wound if it existed. The abridged 5-item version of the International Index of Erectile Function (IIEF-5) score system and the erection hardness scale (EHS) were used to assess erection restoration; preoperative data were based on masturbation; additionally, a radio-opacity index was used for comparison of the femoral cortex and that of penile crus preoperative and postoperative, respectively. Follow-up was primarily made via either INTERNET or telephone yearly. After this May, we introduced an autologous venous patch to augment the crural hypoplasia with a promising outcome on two new patients. Statistically, IBM SPSS 21.0 was used. Results The follow-up time was from 0.1 to 10.0 years, averaging 5.7 ± 1.1 years in the CDG and NCG groups, respectively. The blood loss is negligible. There is no difference between the operation time (4.9−0.8 hours vs. 4.8 ± 0.7 hours, p&amp;gt; 0.88) for the CG and EG group, respectively. In both groups, there is a significant of IIEF-5 scores, EHS (5.7±2.0 vs. 15.9±2.1, 1.8±0.8 vs. 2.5±0.6; 5.8 ±2.1 vs. 22.4±1.1, 1.8±0.9 vs. 3.6±0.3; both P&amp;lt;0.001) between the CDG and NCG. The preoperative radio-opacity of penile crura was unexceptionally enhanced postoperatively. In the NCG, 89.1% (33/37) are gratified; in contrast, 37.5% are satisfied in the CDG five years postoperatively, although surgery benefit is unexceptional reported. A close follow-up is going on with the two new males. Conclusions Penile crural hypoplasia is an unidentified contributor to primary impotence, although a larger sample size and longer-term follow-up are warranted. Disclosure No.

Clinical features and genetic analysis of a case series of skeletal ciliopathies in a prenatal setting

BackgroundShort-rib polydactyly syndrome (SRPS) refers to a group of lethal skeletal dysplasias that can be difficult to differentiate between subtypes or from other non-lethal skeletal dysplasias such as Ellis-van Creveld syndrome and Jeune syndrome in a prenatal setting. We report the ultrasound and genetic findings of four unrelated fetuses with skeletal dysplasias.MethodsSystemic prenatal ultrasound examination was performed in the second or third trimester. Genetic tests including GTG-banding, single nucleotide polymorphism (SNP) array and exome sequencing were performed with amniocytes or aborted fetal tissues.ResultsThe major and common ultrasound anomalies for the four unrelated fetuses included short long bones of the limbs and narrow thorax. No chromosomal abnormalities and pathogenic copy number variations were detected. Exome sequencing revealed three novel variants in the DYNC2H1 gene, namely NM_001080463.2:c.6809G > A p.(Arg2270Gln), NM_001080463.2:3133C > T p.(Gln1045Ter), and NM_001080463.2:c.337C > T p.(Arg113Trp); one novel variant in the IFT172 gene, NM_015662.3:4540-5 T > A; and one novel variant in the WDR19 gene, NM_025132.4:c.2596G > C p.(Gly866Arg). The genotypes of DYNC2H1, IFT172 and WDR19 and the phenotypes of the fetuses give hints for the diagnosis of short-rib thoracic dysplasia (SRTD) with or without polydactyly 3, 10, and 5, respectively.ConclusionOur findings expand the mutation spectrum of DYNC2H1, IFT172 and WDR19 associated with skeletal ciliopathies, and provide useful information for prenatal diagnosis and genetic counseling on rare skeletal disorders.

Abstract C091: Newly identified Fannyhessea species contributions in HPV infection, cervical dysplasia, and cancer in two Arizonan cohorts

Abstract The vaginal microbiome can impact gynecologic health and disease. It is still unclear the extent to which the microbiome plays in the progression and development of gynecologic cancers. Fannyhessea vaginae is a key vaginal bacterium linked to bacterial vaginosis, HPV acquisition, and cervical cancer. F. vaginae was recently proposed for reclassification as three species: F.vaginae, Fannyhessea massiliense, and Fannyhessea species type 2. We hypothesize that these Fannyhessea species vary in terms of their host-microbe interactions which contribute to cancer progression/severity. We investigated the prevalence of Fannyhessea species in two of our Arizona-based HPV and cervical cancer cohorts recruited in Phoenix or Flagstaff area. The Phoenix (Phx) cohort included: women diagnosed with invasive cervical cancer (ICC=9), high-grade squamous intraepithelial lesion (HSIL=27), and low-grade squamous intraepithelial lesion (LSIL=11), as well as controls who were either HPV-positive=20 or HPV-negative without dysplasia=31. While the Flagstaff cohort (Flg) consisted of 31 women that were HPV-positive=7 or HPV-negative=24. The 16S rDNA sequencing information was analyzed with DADA2 and QIIME2 to identify the microbial composition of the cervicovaginal profiles of these patients. Statistical analyses are ongoing, utilizing survey data on these species to decipher their clinical associations with factors such as HPV status and genotype. The cohorts had a prevalence of 59.2% of Atopobiaceae bacteria in Phx and 38.7% prevalence in Flg cohort. We observed F. vaginae (50% and 38.7%, respectively), Fannyhessea species type 2 (16.4% and 25.0%, respectively), F. massiliense (21.0% and 18.8%, respectively) in these cohorts. Interestingly, in both dysplasia groups of the Phx cohort these species had an increased abundance, but it did not reach significance. Other clinical and demographic factors in both cohorts, vaginal pH (p = 0.0005 and 0.47, respectively), Native American race (p=0.002) and Hispanic ethnicity (p= 0.013 and 0.63, respectively), indicated significant species-specific differences in the prevalence of Atopobiaceae. Additionally, genital inflammation scores were higher in profiles that contained Atopobiaceae species (p= 0.05) in Phoenix cohort. In addition, microbial co-occurrence analysis identified that Fannyhessea species highly co-occurred with one another. Sneathia amnii, Sneathia sanguinegens, and other BV-associated bacteria also co-occurred with Fannyhessea species, indicating an association between multiple Fannyhessea species and a potential link to cancer that requires further investigation. This research highlights potential associations of BV-associated bacteria and their role in HPV infection and cervical cancer and investigates the relationship of underexplored Fannyhessea species in historically understudied populations that have the highest disease burden. The overall data from our study provide foundational knowledge on putative oncogenic bacteria that could be exploited to modulate the microbiome and improve cancer outcomes. Citation Format: Nicole R. Jimenez, Paweł Łaniewski, Naomi R. Lee, J. Gregory Caporaso, Melissa M. Herbst-Kralovetz. Newly identified Fannyhessea species contributions in HPV infection, cervical dysplasia, and cancer in two Arizonan cohorts [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C091.

A Modified Approach to Measuring Femoro-Epiphyseal Acetabular Roof (FEAR) Index Has Better Intraobserver and Interobserver Reliability Compared With the Original FEAR Index

PurposeTo propose a modified approach to measuring femoro-epiphyseal acetabular roof (FEAR) index while still abiding by its definition and biomechanical basis, and to compare the intra- and inter-observer reliabilities of the original and the modified FEAR index. To propose a classification for medial sourcil edges. MethodsWe retrospectively reviewed a consecutive series of patients treated with periacetabular osteotomy and/or hip arthroscopy at a single institute. Patients with unilateral or bilateral symptomatic borderline hip(s) were included. Hips with remarkable osteoarthritis, deformities, history of previous surgery, or without symptoms were excluded. A modified FEAR index was defined using a best-fit circle to determine the sourcil line and two ancillary lines connecting femoral head and sourcil edges to determine epiphyseal line. Lateral center-edge angle, Sharp’s angle, Tonnis angle on all hips, as well as FEAR index with original and modified approaches were measured. Intra- and inter-observer reliability were calculated as intraclass correlation coefficients (ICC) for FEAR index with both approaches and other alignments. A classification was proposed to categorize medial sourcil edges. ICC for the two approaches across different sourcil groups were also calculated. ResultsAfter reviewing 411 patients, 49 were finally included. Thirty-two patients (40 hips) were identified as having borderline dysplasia defined by an LCEA of 18 to 25 degrees. Intra-observer ICC for the modified method were good to excellent for borderline hips; poor to excellent for DDH; moderate to excellent for normal hips. As for inter-observer reliability, modified approach outperformed original approach with moderate to good inter-observer reliability (DDH group, ICC=0.650; borderline dysplasia group, ICC=0.813; normal hip group, ICC=0.709). The medial sourcil edge were classified to 3 groups upon its morphology. Type II (39.0%) and III (43.9%) sourcils were the dominant patterns. The sourcil classification had substantial intra-observer agreement (observer 4, kappa=0.68; observer 1, kappa=0.799) and moderate inter-observer agreement (kappa=0.465). Modified approach to FEAR index possessed greater inter-observer reliability in all medial sourcil edge patterns. ConclusionThe modified FEAR index has better intra- and inter-observer reliability compared with the original approach in all hip groups and sourcil groups. Type II and III sourcils accounts for the majority to which the modified approach is better. Level of EvidenceLevel II, Development of diagnostic criteria (consecutive patients with consistently applied reference standard and blinding)

Moyamoya disease/cerebral vasculopathy in osteopathia striata with cranial sclerosis: a rare but important complication.

Osteopathia striata with cranial sclerosis (OSCS) is a rare X-linked dominant sclerosing osteodysplasia, due to AMER1 pathogenic variants. Characteristic features include craniofacial sclerosis and long-bone metaphyseal striations. Moyamoya disease (a type of progressive cerebral vasculopathy) and other types of cerebral vascular disease are not currently clearly associated with OSCS (except for two separate case reports), and can often first present with stroke. Through informal networks with UK-based bone experts and the UK skeletal dysplasia group, three cases from the UK and Ireland were identified. Medical literature was also reviewed to identify the known cases of OSCS with the described complications. We report four females, in whom OSCS and cerebral vasculopathy co-exist, with varying clinical outcomes. There appears to be an emerging association between OSCS and cerebral vasculopathy, which pre-disposes patients to stroke. Given this, screening OSCS patients for cerebral vasculopathy may be of value, especially pre-surgery. Further research regarding optimal screening and management is needed. The mechanism of cerebral vasculopathy and its progression remain unclear.

Adalimumab Experience in the Management of Hidradenitis Suppurativa Burdened with Rapp-Hodgkin Syndrome

Background. Rapp-Hodgkin syndrome is a rare genetic disease from the ectodermal dysplasia group. It manifests with damage of ectodermal structures — layer of embrional tissue that provides the development of many organs and tissues in the body, such as: skin, sweat glands, hair, teeth, and nails. Disease symptoms may range from mild to severe and include dental abnormalities, fragile, thin or no hair, abnormal nails, hypohidrosis (due to the reduced number of sweat glands), cleft lips and palate. Hidradenitis suppurativa is a chronic inflammatory disease that predominantly affects apocrine glands areas. This nosology is characterized by painful nodes, abscesses, and fistulas, prone to relapses and leading to scarring.Clinical case description. The authors present a clinical case demonstrating the combination of Rapp-Hodgkin syndrome and severe hidradenitis suppurativa in 17-year-old male patient.Conclusion. The heterogeneous clinical findings of hidradenitis suppurativa and history of rare genetic disease result in patients' admissions to various medical specialists. Thus, it leads to delayed verification of the diagnosis and incorrect treatment methods. As a result, patients have persistent cosmetic skin defects, possible complications of irrational treatment, and decreased quality of life by the time of diagnosis.

Real-Time PCR Detection of Candida Species in Biopsy Samples from Non-Smokers with Oral Dysplasia and Oral Squamous Cell Cancer: A Retrospective Archive Study.

The impact of Candida sp. in the development of oral cancer remains uncertain and requires sensitive analytical approaches for clarification. Given the invasive capabilities of these microorganisms in penetrating and invading host tissues through hyphal invasion, this study sought to detect the presence of five Candida sp. in oral biopsy tissue samples from non-smoker patients. Samples were obtained from patients at varying stages of oral carcinogenesis, including dysplasia, carcinoma in situ, OSCC, and histologically benign lesions, and analyzed using Real-Time PCR. Oral tissue samples from 80 patients (46 males and 34 females) were included. Significantly higher C. albicans presence was detected in the mild/moderate dysplasia group compared to the healthy (p = 0.001), carcinoma in situ (p = 0.031) and OSCC groups (p = 0.000). Similarly, C. tropicalis carriage was higher in tissues with mild/moderate dysplasia compared to healthy (p = 0.004) and carcinoma in situ (p = 0.019). Our results showed a significant increase in the presence of C. albicans and C. tropicalis within the mild/moderate dysplasia group compared to other cohorts. Coexistence of these two microorganisms was observed, suggesting a potential transition from a commensal state to an opportunistic pathogen, which could be particularly linked to the onset of oral neoplasia.