Explore the vast range of titles available.

Background: Sperm morphology is an important qualitative parameter in semen analysis. Aim: To assess qualitative defects in the semen with normal sperm counts. Setting and Design: This was a prospective and descriptive study done in a tertiary care center. Materials and Methods: Seventy-five semen samples with normal sperm counts were evaluated. Qualitative defects of sperms on Papanicolaou-stained slides were assessed. The defects were noted as follows: head (tapering head, large head, small head, round head, bifid head), middle piece (bent neck, broad middle piece, excess residual cytoplasm), and tail (coiled tail). Results: All cases showed the qualitative defects in spite of the normal counts. The defects found in head - pointed/tapering head (1%-20%), round head (1%-7%), large head (1%-3%) and others (0%-2%); in middle piece - bent neck (1%-8%), excess cytoplasm (1%-3%) or broad middle piece (1%-12%); and in tail - coiled tail (1%-5%). Conclusions: Qualitative defects are often seen even in cases with normal sperm counts.

Context: Core-needle biopsy (CNB) is a minimally invasive screening and diagnostic tool which provides intact tissue fragments for histopathological examination. Aims: This study was conducted to review the current practices of handling and reporting CNBs performed for core-needle biopsies from four organ systems which are frequently encountered in our institution. These include breast, prostate, soft tissues, and lymph nodes. Settings and Design: This was a retrospective study conducted at a tertiary care hospital. Materials and Methods: CNB reports of breast, prostate, soft tissue, and lymph nodes were accessed and categorized based on the site of biopsy, number, and average length of the cores. The CNB reports were categorized into diagnostic or nondiagnostic. In case of diagnosis of malignancy, reports were recorded as structured or nonstructured reports. Statistical Analysis Used: Fisher's exact test and Chi-square tests were applied to check the significance of the results obtained on comparing the number of cores and size of cores with the outcome of report. Results: Out of 16,300 surgical pathology specimens received, 400 were CNBs comprising breast (n = 211), prostate (n = 108), soft tissue (n = 50), and lymph node (n = 31). Majority of the CNBs had 2-5 cores and the size of the core was ≥0.5 cm, which accounted for most of the reports which were diagnostic. There was a lack of clinical and radiological detail in many of the cases. Out of the malignant cases diagnosed, structured reports were given in 30% of breast, 79.3% of prostate, 41.7% soft tissue, and 60% of lymph node needle biopsies. Conclusions: The audit helped to identify areas of improvement in CNB services.

Background New-onset diabetes after transplantation (NODAT) is a serious complication after a solid organ transplant. NODAT occurs in 2% to 53% of all solid organ transplant recipients.1 Tacrolimus is an immunosuppressive agent associated with diabetogenic potential which predominantly is a result of suppression of insulin secretion from pancreatic beta cells. Diabetic ketoacidosis as the first presentation of new onset tacrolimus induced diabetes is rare. We report a case of diabetic ketoacidosis (DKA) in a patient without prior history of diabetes mellitus and receiving tacrolimus as part of immunosuppressive regime post-renal transplant. Clinical Case A 62-year-old female with past medical history of autosomal polycystic kidney disease status-post deceased donor renal transplant and hypertension presented with weakness and fatigue. She had undergone transplant 8 months prior to this presentation and her immunosuppressive regime consisted of mycophenolate mofetil and tacrolimus. The patient was encephalopathic on arrival with normal vitals. Laboratory evaluation was significant for blood glucose of 673, bicarbonate of <10, anion gap of 24, Beta-hydroxybutyrate >8 and a pH of 7.19 on arterial blood gas analysis thus confirming diagnosis of diabetic ketoacidosis (DKA). Tacrolimus level was elevated at 35.7. Intravenous fluids and insulin were initiated with resolution of symptoms and DKA. She was transitioned to a basal-bolus insulin regimen. Further labs revealed Hemoglobin A1C of 11.6% (no previous value), negative insulin antibodies and glutamic acid decarboxylase antibody, and a low C-peptide level at 0.47 (when blood glucose was 150mg/dl). Her tacrolimus dose was adjusted, and she was discharged on a basal-bolus insulin regimen. On follow up, the patient had lower insulin requirements with improvement in C-peptide level to 1.8, thus, indicating beta cell dysfunction in setting of supratherapeutic tacrolimus levels. Conclusion Tacrolimus remains the preferred immunosuppressive agent after kidney transplantation given lower incidence of acute rejections and better tolerance. However, due to its toxic effects on pancreatic beta cells it is imperative blood sugar levels should be routinely monitored in patients on tacrolimus. Appropriate monitoring can lead to timely diagnosis and successful outcomes. Further studies are required to investigate risks factors associated with tacrolimus induced DKA. References 1. Pham PT, Pham PM, Pham SV, Pham PT, Pham P. New onset diabetes after transplantation (NODAT): an overview. Diabetes Metab Syndr Obes. 2011;4: 175-186, https://doi.org/10.2147/DMSO.S19027 Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

The few studies on repeat aspiration focussed on accuracy of diagnosis following repeat. Numbers and documented reasons for repeat remain unaddressed. To study factors associated with requests for repeat fine needle aspiration cytology (FNAC). Metropolitan hospital, clinical audit. Audit of 5104 FNAC in 10 months. Univariate, and multivariate binary logistic regression. Seven hundred and six patients (13.8%) were advised repeat aspirates. Three hundred and twelve of these were actually repeated (44.1%). Carryover of actually repeated aspirates to subsequent months averaged 10.8 (34.2%). Maximum numbers of repeat requests were from thyroid 76/415 (18.3%), followed by lymph node 310/1856 (16.7%), and from breast 86/716 (12.0%). Outcome of actually repeated aspirates were: Diagnostic 181/312 (58.0%), and non-diagnostic 131/312 (41.9%). Reasons for repeat were inadequate aspirates 370/706 (52.4%), non-diagnostic descriptive reports 309/706 (43.7%); in 27/706 (3.8%), no reason was mentioned. Inadequate aspirates, non-diagnostic descriptive reports, and FNAC/FNAB from thyroid, lymph nodes, and breast contribute to repeats. We suggest steps to reduce the number of repeat aspirates to eliminate extra work.

Human chorionic gonadotropin (hCG)-induced hyperthyroidism has been previously reported as a rare paraneoplastic syndrome in non-seminomatous germ cell tumours and usually presents with mild symptoms or subclinical thyrotoxicosis. We present a case of a young adult man who consulted with abdominal pain, nausea and emesis. On admission, he was found to be tachycardic, febrile, anxious and with icteric sclera and tenderness to palpation in the right upper abdomen. A right scrotal mass was also noted. Initial studies revealed transaminitis, hyperbilirubinaemia, suppressed thyroid-stimulating hormone and elevated free T4. Scrotal biopsy confirmed diagnosis of testicular choriocarcinoma with an elevated hCG level of 6074 mIU/mL, which was corrected to 6 760 713 mIU/mL when reassessed with dilution. The clinical scenario reflected hCG-induced thyrotoxicosis concerning for thyroid storm. Euthyroid state was restored after initiation of chemotherapy and a short course of methimazole. Unfortunately, the patient passed away due to progression of his malignant disease. This case suggests that when choriocarcinoma is suspected, the use of iodinated contrast agents should be limited to avoid precipitation of thyroid storm or worsening of hCG-induced hyperthyroidism. Moreover, if the clinical picture does not support a primary aetiology of hyperthyroidism and hCG is not concordantly elevated, reassessment of hCG by dilution should be considered as hCG assays are subject to prozone effect.

Background: The beta subunit of human Chorionic Gonadotropin (hCG) and TSH are very similar and hCG is known to weakly bind the TSH receptor. hCG induced hyperthyroidism has been previously reported as a rare paraneoplastic syndrome in non-seminomatous germ-cell tumors and usually presents with subclinical thyrotoxicosis. We present a noteworthy case of thyroid storm in a patient with hCG producing testicular Choriocarcinoma. Clinical case: A 19-year-old Hispanic man presented to an outside emergency department (ED) with one day of abdominal pain, nausea, recurrent emesis and subjective fever. He had presented to the same ED 9 days prior with similar symptoms which prompted contrasted CT Abdomen/Pelvis demonstrating hepatic masses and a large right testicular mass, suspicious for primary testicular malignancy. On return evaluation, he was noted to have tachycardia with HR 165, mild scleral icterus, tenderness to palpation of right upper quadrant, abdominal pain and a right scrotal mass (5x5 cm). CBC revealed; WBC 12.0 k/uL (n: 4-10.8), AST: 428 u/L (n: 3-34); ALT: 176 u/L (n: 15-41); total bilirubin: 6.3 mg/dL (n: 0.2-1.3), TSH <0.005 uIU/mL (n: 0.4-4.0) and FT4 5.02 ng/dL (n: 0.7-1.4). Clinical scenario was consistent with thyrotoxicosis concerning for thyroid storm (Burch-Wartofsky Point Scale: 50) requiring intensive care for which he was transferred to our institution. Thyroid US revealed increased thyroid vascularity without nodularity. Laboratory workup revealed negative TG Ab, Anti-TPO Ab, TRAb, and TSIG. Conversely, TBG was elevated at 31.2 mcg/ml (n: 13-30). Initial hCG level was obtained as 6,074. After re-testing with dilution was specifically requested, initial hCG was corrected to 6,760,713. Oncologic workup confirmed diagnosis of hCG producing testicular choriocarcinoma with liver and lung metastases. On admission, he was started on oral methimazole and propranolol as well as intravenous steroids which led to marked symptomatic improvement and normalization of FT4 to 1.37 allowing for discontinuation of antithyroid medication on 7th day of hospitalization. He completed 1 cycle of cisplatin/etoposide and experienced marked reduction of his hCG level to 951,460 which correlated with improvement of his TFTs and resolution of his hyperthyroid symptoms. Conclusion: A low threshold of suspicion should be maintained for the possibility of hyperthyroidism in patients with suspected testicular choriocarcinoma, particularly in the context of recent iodinated contrast imaging. If the clinical picture does not support a primary etiology of hyperthyroidism and hCG is not concordantly elevated, re-assessment of hCG by dilution should be considered as hCG assay is also subject to prozone (hook) effect. Hyperthyroidism should be actively managed and closely monitored as response to treatment can be rapid.

Isocitrate dehydrogenase 1 (IDH1) mutations occur in approximately 13% of patients with intrahepatic cholangiocarcinoma, a relatively uncommon cancer with a poor clinical outcome. The aim of this international phase 3 study was to assess the efficacy and safety of ivosidenib (AG-120)—a small-molecule targeted inhibitor of mutated IDH1—in patients with previously treated IDH1-mutant cholangiocarcinoma. This multicentre, randomised, double-blind, placebo-controlled, phase 3 study included patients from 49 hospitals in six countries aged at least 18 years with histologically confirmed, advanced, IDH1-mutant cholangiocarcinoma who had progressed on previous therapy, and had up to two previous treatment regimens for advanced disease, an Eastern Cooperative Oncology Group performance status score of 0 or 1, and a measurable lesion as defined by Response Evaluation Criteria in Solid Tumors version 1.1. Patients were randomly assigned (2:1) with a block size of 6 and stratified by number of previous systemic treatment regimens for advanced disease to oral ivosidenib 500 mg or matched placebo once daily in continuous 28-day cycles, by means of an interactive web-based response system. Placebo to ivosidenib crossover was permitted on radiological progression per investigator assessment. The primary endpoint was progression-free survival by independent central review. The intention-to-treat population was used for the primary efficacy analyses. Safety was assessed in all patients who had received at least one dose of ivosidenib or placebo. Enrolment is complete; this study is registered with ClinicalTrials.gov, NCT02989857. Between Feb 20, 2017, and Jan 31, 2019, 230 patients were assessed for eligibility, and as of the Jan 31, 2019 data cutoff date, 185 patients were randomly assigned to ivosidenib (n=124) or placebo (n=61). Median follow-up for progression-free survival was 6·9 months (IQR 2·8–10·9). Progression-free survival was significantly improved with ivosidenib compared with placebo (median 2·7 months [95% CI 1·6–4·2] vs 1·4 months [1·4–1·6]; hazard ratio 0·37; 95% CI 0·25–0·54; one-sided p<0·0001). The most common grade 3 or worse adverse event in both treatment groups was ascites (four [7%] of 59 patients receiving placebo and nine [7%] of 121 patients receiving ivosidenib). Serious adverse events were reported in 36 (30%) of 121 patients receiving ivosidenib and 13 (22%) of 59 patients receiving placebo. There were no treatment-related deaths. Progression-free survival was significantly improved with ivosidenib compared with placebo, and ivosidenib was well tolerated. This study shows the clinical benefit of targeting IDH1 mutations in advanced, IDH1-mutant cholangiocarcinoma. Agios Pharmaceuticals.

Cholangiocarcinoma is an aggressive malignancy with poor overall survival. Approximately 15% of intrahepatic cholangiocarcinomas contain alterations. Infigratinib is an oral FGFR 1-3 kinase inhibitor. Favorable results from a Phase II trial of infigratinib in advanced/metastatic -altered cholangiocarcinomas has led to its further investigation in the front-line setting. In this article we describe the design, objectives and rationale for PROOF 301, a Phase III multicenter, open label, randomized trial of infigratinib in comparison to standard of care gemcitabine and cisplatin in advanced/metastatic cholangiocarcinoma with translocations. The results of this study have the potential to define a new role for a chemotherapy-free, targeted therapy option in the front-line setting for these patients. Clinical Trial Registration: NCT03773302 (ClincalTrials.gov).