Inconclusive Report Research Articles

Left paratesticular mass mimicking polyorchidism: A case report

We report a rare case of primary scrotal lipoma in a 20-year-old patient which clinically mimics a left triorchidism. The patients presented with the left testicular swelling and the ultrasonography of the scrotum revealed an inhomogeneous hyperechoic mass with an inconclusive report. The left scrotal hemi exploration was planned, and intraoperatively, it was found to be a paratesticular mass with an equivalent size corresponding to the left testicle, separate from the left testicle. The histopathology confirms the lipomatous swelling. The post-operative period remains uneventful and the patient has been on follow-up for the past 1 year with no relapse.

OSTEOLYSIS OF THE MANDIBLE AND PERIODONTITIS ASSOCIATED WITH RHEUMATOID ARTHRITIS AND METHOTREXATE

The citrullination process is exaggerated in rheumatoid arthritis, leading to abnormal accumulation of citrulline. Antibodies are released, triggering an autoimmune inflammatory process. Methotrexate, an antimetabolite and antifolate drug, used in arthritis, leads to myelosuppression favoring the appearance of opportunistic infections. Methotrexate therapy has side effects, which include oral manifestations. This report aimed to describe a case of periodontal disease with osteolysis of the mandible associated with rheumatoid arthritis and methotrexate therapy. A 38-year-old female presented a history of tooth mobility. Radiographic examination showed horizontal bone loss exceeding the middle third of the roots, in addition to bone rarefaction throughout the body of the mandible. Fine needle aspiration and an excisional biopsy with curettage of one of the lesions were performed, which yielded an inconclusive report. In the imaging follow-up, bone neoformation was observed in the biopsy region. The citrullination process is exaggerated in rheumatoid arthritis, leading to abnormal accumulation of citrulline. Antibodies are released, triggering an autoimmune inflammatory process. Methotrexate, an antimetabolite and antifolate drug, used in arthritis, leads to myelosuppression favoring the appearance of opportunistic infections. Methotrexate therapy has side effects, which include oral manifestations. This report aimed to describe a case of periodontal disease with osteolysis of the mandible associated with rheumatoid arthritis and methotrexate therapy. A 38-year-old female presented a history of tooth mobility. Radiographic examination showed horizontal bone loss exceeding the middle third of the roots, in addition to bone rarefaction throughout the body of the mandible. Fine needle aspiration and an excisional biopsy with curettage of one of the lesions were performed, which yielded an inconclusive report. In the imaging follow-up, bone neoformation was observed in the biopsy region.

Assessing variants of uncertain significance implicated in hearing loss using a comprehensive deafness proteome

Hearing loss is the leading sensory deficit, affecting ~ 5% of the population. It exhibits remarkable heterogeneity across 223 genes with 6328 pathogenic missense variants, making deafness-specific expertise a prerequisite for ascribing phenotypic consequences to genetic variants. Deafness-implicated variants are curated in the Deafness Variation Database (DVD) after classification by a genetic hearing loss expert panel and thorough informatics pipeline. However, seventy percent of the 128,167 missense variants in the DVD are “variants of uncertain significance” (VUS) due to insufficient evidence for classification. Here, we use the deep learning protein prediction algorithm, AlphaFold2, to curate structures for all DVD genes. We refine these structures with global optimization and the AMOEBA force field and use DDGun3D to predict folding free energy differences (∆∆GFold) for all DVD missense variants. We find that 5772 VUSs have a large, destabilizing ∆∆GFold that is consistent with pathogenic variants. When also filtered for CADD scores (> 25.7), we determine 3456 VUSs are likely pathogenic at a probability of 99.0%. Of the 224 genes in the DVD, 166 genes (74%) exhibit one or more missense variants predicted to cause a pathogenic change in protein folding stability. The VUSs prioritized here affect 119 patients (~ 3% of cases) sequenced by the OtoSCOPE targeted panel. Approximately half of these patients previously received an inconclusive report, and reclassification of these VUSs as pathogenic provides a new genetic diagnosis for six patients.

Excerpt from the 2022 American Association for the Study of Liver Diseases clinical practice guideline: management of primary sclerosing cholangitis and cholangiocarcinoma

What are the new contents of the guideline since 2010?A.Patients with primary and non-primary sclerosing cholangitis (PSC) are included in these guidelines for the diagnosis and management of cholangiocarcinoma.B.Define "related stricture" as any biliary or hepatic duct stricture accompanied by the signs or symptoms of obstructive cholestasis and/or bacterial cholangitis.C.Patients who have had an inconclusive report from MRI and cholangiopancreatography should be reexamined by high-quality MRI/cholangiopancreatography for diagnostic purposes. Endoscopic retrograde cholangiopancreatography should be avoided for the diagnosis of PSC.D. Patients with PSC and unknown inflammatory bowel disease (IBD) should undergo diagnostic colonoscopic histological sampling, with follow-up examination every five years until IBD is detected.E. PSC patients with IBD should begin colon cancer monitoring at 15 years of age.F. Individual incidence rates should be interpreted with caution when using the new clinical risk tool for PSC for risk stratification.G. All patients with PSC should be considered for clinical trials; however, if ursodeoxycholic acid (13-23 mg/kg/day) is well tolerated and after 12 months of treatment, alkaline phosphatase (γ- Glutamyltransferase in children) and/or symptoms are significantly improved, it can be considered to continue to be used.H. Endoscopic retrograde cholangiopancreatography with cholangiocytology brushing and fluorescence in situ hybridization analysis should be performed on all patients suspected of having hilar or distal cholangiocarcinoma.I.Patients with PSC and recurrent cholangitis are now included in the new unified network organ sharing policy for the end-stage liver disease model standard.J. Liver transplantation is recommended after neoadjuvant therapy for patients with unresectable hilar cholangiocarcinoma with diameter < 3 cm or combined with PSC and no intrahepatic (extrahepatic) metastases.

Preventing Uterine Cervix Cancer: The Clinical Meaning of Atypical Glandular Cells.

To determine the prevalence of the atypical glandular cells (AGCs) cytology and to analyze its clinical significance in different age ranges. Retrospective observational study using computerized data from the Brazilian National Cancer Institute, including women screened between January 2002 and December 2008. The women included were those with an AGC result who were properly followed-up with colposcopy and a second cytology. A total of 132,147 cytopathological exams were performed during the study period. Five-hundred and thirty-three (0.4%) women with AGC cytology were identified and, of these, 69.41% (370/533) were properly referred for colposcopy and a new cytology. Most of the women (79.2%) with a 1st or 2nd AGC cytology were between the ages of 25 and 54 years. The 2nd cytology demonstrated 67.6% (250/370) of normality, 24.5% (91/370) of squamous atypia, and 6.2% (23/370) of AGC, 0.8% (3/370) adenocarcinoma in situ and 0.8% (3/370) adenocarcinoma invasor. On biopsy of the women with a second AGC cytology, 43.4% (10/23) had normal histology, 43.4% (10/23) had squamous lesions, 8.7% (2/23) had invasive adenocarcinoma, and 1.2% (1/23) had an inconclusive report. All of the women with high-grade squamous intraepithelial lesion (HSIL) or invasive adenocarcinoma (respectively 5 and 2 patients), after a 2nd AGC cytology were 25 years old or older. The prevalence of the AGC cytology was low in the studied population. Most of the AGC cytology cases occurred in adult women between the ages of 25 and 54. Although most of the patients had normal histology after follow-up, several of them presented with squamous intraepithelial lesions or invasive adenocarcinoma.

LIPOID PROTEINOSIS: A RARE DISEASE IN PEDIATRIC DENTISTRY

This report describes the diagnostic process of lipoid proteinosis, a rare disorder with more than 300 reported cases, in a female child. The patient presented initially as a 7-year-old with multiple, whitish submucosal nodules of a fibrous consistency in the lower lip, but with an inconclusive pathology report. When she was 9 years old, she presented with exacerbation of the original clinical findings, which then involved the upper lip, buccal mucosa, and tongue. Dermatologic lesions were noted on the child’s limbs and face, and the patient had developed a hoarse voice. Histopathologic examination of the buccal mucosa revealed dense connective tissue with hyaline foci, which were positive with periodic acid-Schiff staining and resistant to diastase digestion. MRI revealed calcium deposits in her amygdala, and nasopharyngolaryngoscopy revealed lesions in her vocal cords. The patient is currently stable and under multidisciplinary follow-up, but no treatment has been recommended.

NASAL TYPE T/NATURAL KILLER LYMPHOMA - CASE REPORT

A 55-year-old white female patient was referred to our oral medicine department for evaluation of a palate lesion. Past medical history included of a diagnosis of nasal type natural killer (NK)/T-cell lymphoma being treated. At the extraoral physical examination there was an increase volume in the upper third of the face involving the whole nose. In the mouth, an exophytic lesion was found, which was hard to palpation and painless with areas of ulceration in the hard palate with approximately 60 days since onset. Incisional biopsy was performed with an inconclusive histopathologic report. Immunohistochemical analysis showed positivity for CD3 and CD56 plus Ki67 positivity in 90% of the cells leading to the diagnosis of nasal T-cell lymphoma/NK type. At the time of diagnosis, chemotherapy was started using cyclophosphamide, doxorubicin (hydroxydaunorubicin), vincristine (Oncovin), prednisone protocols that promoted a significant decrease in tumor volume. The patient is currently being followed up with no signs or symptoms of recurrence.

Forensic evaluation of SE33 marker in Indian population using Global Filer, Fusion 6 c and Panglobal autosomal STR multiplex

Capillary electrophoresis based forensic DNA typing using PCR with multiplex STR kit is gold standard now. But even one mismatch in the studied markers results in an inconclusive report. This deficiency is suggested to be taken care of by using alternative markers and/or by increasing the number of STR markers. Three new generation multiplex autosomal STR systems namely GlobalFiler™ PCR Amplification Kit (Thermo Fisher Scientific Foster City, CA, USA), PowerPlex Fusion 6C (Promega, Madison, WI, USA), PanGlobal Human DNA Identification Kit (Health Gene Technologies Co., Ltd) incorporating new 20 CODIS and the SE33 marker were used on 819 samples to observe the forensic performance of SE33 marker. The study presents first forensic evaluation of SE33 marker included in new generation multiplex systems being used for forensic DNA typing. A total of 52 alleles were observed on the SE33 marker in the studied population. Forensic parameters including allele frequency, Power of discrimination, Polymorphism information content, Power of exclusion, Paternity index, Observed and Expected Heterozygosity, Matching Probability, Shannon's Information and Index and Fixation Index are reported for the studied marker.

When next-generation sequencing-based preimplantation genetic testing for aneuploidy (PGT-A) yields an inconclusive report: diagnostic results and clinical outcomes after re biopsy.

To describe diagnostic results following re-biopsy of blastocysts with inconclusive results on preimplantation genetic screening for aneuploidy (PGT-A) and to evaluate the reproductive potential of re-biopsied blastocysts. This retrospective cohort study included all trophectoderm biopsies submitted for PGT-A by a large in vitro fertilization center to a single genetics laboratory from June 2016 to October 2018. PGT-A was performed using next-generation sequencing (NGS). No-result blastocysts that underwent re-biopsy were subsequently classified as euploid, aneuploid, mosaic/segmental, or no-result. Ongoing pregnancy and clinical loss rates were assessed following transfer of re-biopsied blastocysts. Logistic regressions were conducted to account for age and blastocyst morphology. Of the trophectoderm biopsies submitted for PGT-A, 635/25,199 (2.5%) were categorized as no-result. Those that underwent re-biopsy (n = 250) had a 95.2% diagnostic rate with 140 (56.0%) receiving euploid diagnoses. Thirty-six re-biopsied blastocysts deemed euploid were subsequently transferred, resulting in 18 (50.0%) ongoing pregnancies and 5 (13.9%) clinical losses. After adjusting for age and blastocyst morphology, there remained a lower ongoing pregnancy rate and a trend towards higher clinical loss rate following transfer of a re-biopsied blastocyst. When compared to blastocysts that underwent the same number of vitrification-warming cycles but only one biopsy, there were no differences in outcomes. Failure to obtain an analytical result does not change the probability that a given blastocyst is euploid. Pregnancy outcomes following transfer of re-biopsied blastocysts are favorable, but further data must be accrued for an adequately powered comparison with outcomes after transfer of blastocysts biopsied once.

SE33 locus as a reliable genetic marker for forensic DNA analysis systems

Background/aim: Genetic variation, an authentic tool of individual discrimination, is being used for forensic investigations worldwide. A missing result for even one out of 13-17 markers leads to an inconclusive report. Additional reliable markers are required to compensate such deficiencies. The SE33 locus has high genetic variability in different populations and is being used in forensic investigation systems in some countries. The purpose of the study was to assess the viability of use of the SE33 locus as a supportive marker for forensic DNA profiling. Materials and methods: Amplification of the SE33 locus was performed using the PowerPlex ES Monoplex System SE33 (Promega). After genotyping 204 Pakistani individuals, different genetic and forensic parameters for the SE33 locus were studied. Results: Genotyping of the SE33 locus revealed a total of 43 alleles including 3 novel alleles. Significant values of different forensic and genetic parameters including power of discrimination, power of exclusion, and polymorphism information content were observed. Conclusions: Addition of the SE33 locus in forensic DNA profiling may help to produce conclusive reports where results are inconclusive due to degraded evidence samples. The SE33 locus can confidently be used for Pakistani and neighboring populations having common ancestors from Iran to Central Asia, the Middle East, India and Turkey.

Explaining Fetal Death--What Are the Contributions of Fetal Autopsy and Placenta Examination?

The aim of our study was to categorize fetal deaths by different diagnostic groups and see to what extent an autopsy of a presumably normal fetus contributes to the final diagnosis and how many unexplained fetal deaths remain unexplained after examination of the placenta. We reviewed autopsy reports of 351 fetuses with a gestational age of 12 or more weeks at the Department of Pathology and Medical Genetics at St Olavs Hospital during the years 2001 through 2010. In our records, 38.5% (135 of 351) of the deaths were due to noninfectious placenta causes, 31.6% (111 of 351) were caused by infections, and 29.9% (105 of 351) of the fetal deaths remained unexplained after autopsy. We also found that an inconclusive report was more common early in pregnancy. The incidence of fetal loss due to circulatory disturbances in the placenta increased toward term. Infections were evenly distributed in intrauterine fetal deaths, although in spontaneous abortions, they were more frequent during the second trimester. For both explained and unexplained deaths, we observed a bimodal distribution, with peaks in the early second trimester and late third trimester toward term.

English

AIMS AND OBJECTIVES: Mass in the Right Iliac Fossa (RIF) is clinically difficult to differentiate, ultrasonography a quick non-invasive investigation has bridged the gap between clinical examination and direct visualization. The study was done to know the efficacy of ultrasonography in pre operative evaluation of RIF mass. MATERIALS AND METHODS: The data for this prospective study was obtained from 300 patients admitted/ attending OPD with a clinical diagnosis of RIF mass. Ultrasonography was done and a provisional diagnosis was obtained. The final diagnosis was obtained with histopathological examination(HPE) or by other standard methods. The sonological diagnosis was compared with final diagnosis. RESULTS: Out of 300 patients studied 236 were operable. Ultrasonography was able to diagnose 228 out of the 236 (Sensitivity of 96.7%) as operable cases and the remaining eight were inconclusive report. Ultrasonography was able to rule out all non operable cases with 100% specificity. The final diagnosis correlated with sonological diagnosis in 284 cases with sensitivity of 94.6% while clinical diagnosis correlated with final diagnosis in 232 cases with sensitivity of 77.3%.The most common conditions being appendicular mass followed by appendicular abscess and ileocaecal TB. DISCUSSION: Thus ultrasonography in experienced hands is an invaluable tool for preoperative evaluation of RIF mass. It has favorable sensitivity and specificity in differentiating RIF mass and 100% sensitivity and specificity in detecting cases which needs emergency intervention. In countries like India where other radiological investigation modalities are present only in higher center, ultrasonography becomes an invaluable tool in diagnosis and evaluation of RIF mass for practitioners in semi-urban and rural settings.

Incidence and Significance of Inconclusive Results in Ultrasound for Appendicitis in Children and Teenagers

Purpose Frustratingly, sonography to assess for appendicitis in children often leads to an inconclusive report (eg, “suspicious for appendicitis”) or nonvisualization of the appendix. To aid in planning who to image and how to interpret the results, we investigated whether these 2 results were more frequent in teenagers than preteens and the prevalence of appendicitis associated with each result. Methods We retrospectively reviewed sonographic and surgical findings in patients <18 years ( n = 189) referred with clinical suspicion of appendicitis over a 12-month period. Children (≤12.0 years old; n = 86) and teens (>12.0 years old; n = 103) were compared. Results Prevalence of appendicitis was 34% in each group, similar to other centres; 0% for those with negative ultrasound reports (0/35), 10% for nonvisualized appendix (8/84), 68% for inconclusive report (15/22), and 85% for positive ultrasound (41/48). Teens were significantly more likely to have an inconclusive ultrasound. Inconclusive reports were because of borderline findings (eg, appendix size near 6 mm; 9/22), body habitus, bowel gas, or unusual findings due in retrospect to perforation. The rate of nonvisualization of the appendix did not vary significantly with age (42% vs 47%). Conclusion An inconclusive result of ultrasound for appendicitis was significantly more frequent in teens than in preteens and carried a high (68%) likelihood of appendicitis. Conversely, a nonvisualized appendix was equally frequent in teens and preteens, and had a low likelihood of appendicitis (only 10% positive). These findings encourage the use of ultrasound in preteens in particular and can assist interpretation of these common results.

Auditing Autopsies: Lagos University Teaching Hospital Experience

A thirteen-month prospective study was carried out to compare clinical (antemortem diagnosis) with autopsies (post-mortem diagnosis) on patients managed at Lagos University Teaching Hospital (LUTH) between October 1999 and November, 2000. In the study period, a total of 1843 deaths were registered out of which 467 autopsy request were made (hospital and coroner's autopsies). Hospital autopsy request were 411 (88%) while coroner's request constituted 56 (12%) of the autopsies. Only 305 (65%) of the autopsies performed are excluded in the study because of inconclusive clinical report and diagnosis or autopsy not done on them. The result showed that the concordance rate between clinical and autopsy diagnosis was found to be 82.1%: and that 71.9% of deaths occurred within 48 hours of presentation and majority of this category of deaths are the least investigated. Forty five percent (45%) of all the group studied had no clinical investigation done. The low autopsy rate and the attitude of medical practitioners to autopsy do not encourage good medical practice and continue medical education. We need to rely more on autopsy audit to study disease processes and to enhance our diagnostic skill. Autopsy audit should be officially adopted as a means of quality control in hospitals. Nig. Medical Practitioner Vol. 44(5/6) 2003: 96-99

Queer Science: The Use and Abuse of Research on Homosexuality

The author of<i>Queer Science</i>, until recently a neuroscientist at the Salk Institute in San Diego, Calif, researched and in 1991 published in<i>Science</i>his admittedly inconclusive report. In a small postmortem study of the brains of 13 homosexual men with AIDS, he found the interstitial nucleus of the anterior hypothalamus (INAH) was smaller in some than the INAH of comparable heterosexual males. Although limiting factors were the small sample size, the diagnosis of AIDS, and medications used, the as yet unreplicated findings did stir up renewed interest and longstanding academic, social, personal, philosophical, moral, media, and legal questions about a possible anatomic cause of homosexual orientation (gender identity and feelings). The 295-page text has 50 additional pages of references and notes. It attempts to gather the research objectively, while the message comes through strongly: gays are born that way. The title's "Queer" may perhaps be trendy, cute, or tongue-in-cheek

Assisting suicide in Michigan.

Perhaps no American state has seen more legal activity on assisting suicide than Michigan, but despite legislation, a study Commission, several legal cases and a state Supreme Court ruling, the state seems much further from a humane resolution of the question than when the activities of Dr. Jack Kevorkian began in June of 1990. This note summarizes major legal events over a twelve-month period (ending May '95), which included jury acquittal of Dr. Kevorkian, the inconclusive report of the Michigan Commission on Death and Dying, the failure of the state legislature to enact legislation to replace the expired absolute but temporary prohibition, and the decision of the Michigan Supreme Court in Mich. v. Kevorkian declaring assisting suicide a common law felony and ruling that in certain circumstances a person assisting suicide can be prosecuted for murder. The Commission's model decriminalization proposal and the bills subsequently introduced in the legislature (all of which to varying degrees surrounded assisting suicide with restrictions and safeguards), as well as the decision of the Supreme Court, are discussed. Certain puzzling features of the latter, especially with regard to the kind of causation that can turn helping another commit suicide into murder are noted.

Biological aspects of antiandrogens

Flutamide (α,α,α-trifluoro-2-methyl-4'-nitro-m-propionotoluidide) at daily doses from 1–50 mg/kg reduced seminal vesicle and ventral prostate weights of intact male rats. A comparative study in castrated rats revealed that flutamide was equipotent to cyproterone acetate (CPA) as an antiandrogen. These potencies were substantiated by a newly developed assay measuring DNA synthesis rate (Sufrin and Coffey). No androgenic, estrogenic, anti-estrogenic, corticoid, progestational, anti-progestational, or antigonadotrophic activities were observed. Flutamide, given per os daily for either 6 weeks or 1 year to aged dogs with benign prostatic hyperplasia, reduced prostatic size in 6 weeks and the prostate remained reduced at 3, 6 and 12 months after the initiation of drug therapy. Flutamide, given im three times weekly for 4 weeks reduced the size of the baboon prostate (Müntzing et al.). In testosterone propionate-treated castrated rats CPA and flutamide inhibited 3H-testosterone uptake and retention by prostate and prostate nuclei. In a study in 18 patients with far-advanced carcinoma of the prostate, there were seven positive responders, 10 failures and one inconclusive report, following the daily administration of flutamide (Stoliar and Albert). In a similar study, 9 of 12 patients in stage D prostatic carcinoma responded favorably (Prout and Irwin).