bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost-effectiveness of NALIRIFOX compared to other first-line treatments for metastatic pancreatic cancer.
Authors: Tan Chia Jie , Liu Haopeng , Farrokhi Pegah , Garrido-Laguna Ignacio , Stenehjem David D.
Published: January 2025

733

Background:
NALIRIFOX was recently approved for first-line treatment of metastatic pancreatic cancer, where combination chemotherapy remains the main treatment modality. We conducted a cost-effectiveness analysis of NALIRIFOX compared to both FOLFIRINOX and gemcitabine/protein-bound paclitaxel (GP).
Methods:
A partitioned survival model with three health states (progression-free, post-progression and death) was constructed to model the disease course. Using published data from NAPOLI-3, parametric survival curves were generated for NALIRIFOX, from which survival curves for FOLFIRINOX and GP were extrapolated using pooled efficacy data reported by a network meta-analysis of clinical trials. Model inputs were retrieved from the literature or other publicly available resources. Specifically, drug acquisition costs were from average wholesale prices in the Red Book while administration, disease monitoring and supportive care costs were from the CMS Physician Fee Schedule. Utility values to estimate quality-adjusted life years (QALY) were from the CALGB80303 trial. Adverse effects that were considered included anemia, neutropenia, febrile neutropenia, thrombocytopenia, diarrhea, peripheral neuropathy, nausea and vomiting, and fatigue. Adverse effect rates were based on data pooled from clinical trials while costs and disutility were obtained from a secondary analysis of claims data and a clinician survey, respectively. The time horizon was 5 years and utilized a third-party payer perspective. Both costs ($USD 2024) and outcomes were discounted at 3% annually. A probabilistic sensitivity analysis was conducted by varying model parameters based on 95% confidence intervals if known or 10% in both directions otherwise.
Results:
The overall cost associated with NALIRIFOX was $129,314, followed by GP ($104,593) and FOLFIRINOX ($41,528). Among the 3 regimens, NALIRIFOX incurred the highest treatment-related cost ($105,533) but the lowest adverse effects management cost ($16,541). On average, patients on NALIRIFOX gained a total of 1.14 life years (LY) or after adjusting for utility, 0.86 QALY. FOLFIRINOX led to 1.09 LY or 0.82 QALY while GP resulted in 0.99 LY or 0.75 QALY. Due to its higher cost and lower survival benefit, GP was dominated by FOLFIRINOX. Compared to FOLFIRINOX, the incremental cost-effectiveness ratio (ICER) of NALIRIFOX was $1,952,062/QALY. In our sensitivity analysis, the probability of NALIRIFOX being cost-effective was 0% at all conventional ICER thresholds up to $200,000/QALY.
Conclusions:
Due to the high drug acquisition cost, the ICER of NALIRIFOX far exceeds currently acceptable thresholds for economic value and NALIRIFOX is considered not cost-effective. This is despite that in our model among first line treatments for metastatic pancreatic cancer, NALIRIFOX was associated with reduced costs for managing adverse effects.
A systematic review and meta-analysis on evaluating the efficacy and safety of netupitant/palonosetron compared to aprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients undergoing emetogenic chemotherapy.
Authors: Maryam Bibi , Shahzil Muhammad , Mukhopadhyay Debduti , Irfan Mariyah Zainab , Muhammad Anza , Khan Faiza , Ashraf Aqsa
Published: January 2025

823

Background:
NEPA stands as the exclusive oral fixed combination antiemetic agent, comprising the highly selective NK1 receptor antagonist (RA) netupitant (300 mg) and the clinically distinct 5-HT3 RA, palonosetron (0.5 mg). Administered in a single dose, NEPA concurrently modulates two critical antiemetic pathways, offering a more convenient and straightforward alternative for sustained protection against chemotherapy-induced nausea andvomiting (CINV). Numerous studies have assessed NEPA's efficacy relative to other Neurokinin (NK) 1 receptor antagonists (RAs), notably aprepitant (APR), widely utilized for CINV. Our study critically examines the efficacy and safety of NEPA versus APR for preventing CINV in patients receiving emetogenic chemotherapy, drawing insights from recent studies.
Methods:
Studies comparing NEPA versus APR for the prevention of CINV in patients receiving emetogenic chemotherapy until August 2024 were systematically searched on Medline, Embase, and Cochrane Library. Notably, no systematic review or meta-analysis of pooled data from existing studies is currently present in the literature.
Results:
Following screening, four studies were deemed eligible for inclusion in the meta-analysis, encompassing a total of 2079 patients. The NEPA group comprised 1047 individuals, while the APR group comprised 1032 subjects. The primary outcome included the comparison of subjects experiencing no nausea in overall phases. Secondary outcomes involved subjects with no emesis and no nausea in the acute and delayed phases. A significant reduction in the risk of overall nausea in the NEPA group was observed compared to the APR group after Moderately Emetogenic Therapy (MEC) or Highly Emetogenic Therapy (HEC) [Risk Ratio (RR) of 1.07, 95% Confidence Interval (CI) = 1.01-1.13, P = 0.01). A trend of reduced emesis during both acute [RR = 1.08, 95% CI = 0.95-1.22, P = 0.24] and delayed periods [RR = 1.03, 95% CI = 0.99-1.07, P = 0.15] was observed in the NEPA group, but the results were not statistically significant. Significant nausea in the acute and delayed post-chemotherapy periods exhibited a similar trend (RR = 1.02, 95% CI = 0.98-1.06, P = 0.43) and (RR = 1.04, 95% CI = 0.98-1.10, P = 0.23) respectively, with non-significant statistical outcomes.
Conclusions:
Our analysis suggests that the use of NEPA results in better control of nausea in overall phases compared to Aprepitant for the prevention of CINV in patients receiving emetogenic chemotherapy. However, NEPA demonstrates comparable efficacy to aprepitant in achieving control of nausea and emesis when the symptoms are stratified in acute and delayed phases. Nevertheless, further studies are warranted for a comprehensive comparison between NEPA and Aprepitant for the prevention of CINV.
Long-term outcomes of total neoadjuvant treatment (TNT) for locally advanced rectal cancer: Maria Sklodowska Curie National Cancer Research Institute (MSCNCRI) cohort from Polish-II study.
Authors: Winiarek Mariola , Marcisz-Grzanka Katarzyna , Wyrwicz Lucjan
Published: January 2025

84

Background:
The data on long-term outcomes of TNT for locally advanced rectal cancer are still limited. The Polish-II study randomized 515 cT4/fixed cT3 rectal cancer to pre-operative chemoradiation (CRT) with 5fu/oxaliplatin or 5x5 Gy radiotherapy with consolidating chemotherapy (TNT). Despite the early separation of survival curves with benefit for TNT, the outcomes at the longer observation were similar reaching 49% in both arms surviving at 8 years. Here, we present the long-term oncological and functional outcomes of patients recruited to the study in MSCNCRI along with the quality of life in survivors at >10 years of observation.
Methods:
Of 180 patients treated in the study in MSCNCRI 88 and 92 pts were randomized to TNT and CRT arms, respectively. The long-term follow-up was performed according to the standard protocol, FACT-C and EORTC QLQ-C30 scales were used to assess the functional outcomes.
Results:
Median survival in the TNT group and CRT was 115 and 61 months (p=0.191). At the cut-off in March 2023, 53.4% and 61.1% of pts died in the TNT and CRT group (p = 0.375). In the TNT group, 73.9% of deaths were attributed to cancer corresponding to 81.8% in CRT (p = 0.725). Late relapses diagnosed over 5 years from the end of the active treatment were identified in 5 of 94 patients in the follow-up (1 local recurrence in the TNT group, 4 patients with lung metastasis – 3 in TNT with one having also CNS relapse - and 1 in CRT). All late relapses in the TNT group could be salvaged with local therapies. Regarding long-term quality of life, no differences were observed in FACT-C and EORTC QLQ C30 in patients treated with either arm: QLQ C30 – TNT: 50.68 ± 12.74 in the range 34.00- 79.00; CRT: 48.61 ± 11.39 in the range 34.00-70.00 (p = 0.507); FACT-C - TNT: 113.00 in the range 42.00-136.00; CRT: 118.00 in the range 74.00-136.00; p=0.252). No difference in physical, family, and emotional status was observed. At the ultimate observation, stoma was present in 40.5% and 40.6% of TNT and CRT groups, respectively (p>0.999).
Conclusions:
In this randomized cohort, after more than 10 years of observation TNT led to numerically longer OS than CRT, although this was not statistically significant. The functional outcomes of the long-term survivors are similar in both cohorts. Late relapses are rare but could be salvaged in most cases. This study further supports the use of TNT in patients with locally advanced rectal cancer.
Clinical trial information: NCT00833131
.
A phase 2, multicenter, open-label study of AlloStim combined with anti-PD-L1immunotherapy as 4L therapy in patients with MSS/pMMR metastatic colorectal cancer.
Authors: Har-Noy Michael , Lausoontornsiri Wirote
Published: January 2025

TPS318

Background:
Microsatellite stable (MSS)/mismatch repair proficient (pMMR) metastatic colorectal cancer (mCRC) are immunologically 'cold' tumors that do not respond to immunotherapy. Cold tumors represent a formidable hurdle for checkpoint blockade immunotherapy approaches. Therefore, there is a need for novel strategies that could reprogram mCRC cold tumors to become inflamed hot tumors in a manner that might potentially convert low tumor mutational burden (TMB) tumors into checkpoint blockade responsive tumors. AlloStim is an experimental allogeneic, non-genetically manipulated, Th1-like activated living cell immunotherapy derived from healthy unrelated blood donors. The mechanism of action is designed to convert immunologically cold tumors into inflamed hot tumors. A case study of a single 3L MSS/pMMR mCRC patient primed with AlloStim followed by combination anti-PD-1/anti-CTLA4 checkpoint blockade resulted in a rare objective tumor response (Hirschfeld, et al, Translational Medicine Communications (2024) 9:15). The AlloStim priming results in an abundance of infiltrating interferon-gamma producing Th1 cells. Interferon-gamma has been shown to increase expression of PD-L1 in the TME. Therefore, it is hypothesized that the combination of AlloStim with an anti-PD-L1 checkpoint inhibitor might optimally evoke anti-tumor immune responses in this immunotherapy-refractory MSS/pMMR mCRC population.
Methods:
The study is a phase 2, multicenter, single-arm clinical trial of MSS/pMMR mCRC subjects in 4L that have been previously treated with an oxaliplatin-containing and irinotecan-containing chemotherapy regimen, anti-EGFR (RAS wt and left-sided), anti-VEGF and have progressed on 3L TAS-102 +/- bevacizumab or regorafenib or fruquinitinib. The study is evaluating weekly AlloStim priming from day 0 to day 49 followed by combination of AlloStim IV infusion (q2w) followed a week later by anti-PD-L1 (avelumab 800mg/q2w) from days 63 to day 98. Objective tumor response and disease control rate are the primary end-points. Overall survival is the secondary end-point. Clinically stable patients at day 112 can continue in an expansion phase with another round of combination AlloStim and avelumab from day 119 to day 154. CT scans are conducted at baseline, day 56 after AlloStim priming, day 112 after combination of alternating q2w infusions of AlloStim and avelumab and day 168 in all patients. CT scans will be analyzed by independent central readers using RECIST 1.1. Up to 50 patients will be enrolled with an interim analysis performed to assess efficacy after 20 patients become evaluable. The study is open and has not yet enrolled any patients at time of submission.
Clinical trial information: NCT06557278
.
Phase II single-arm, single-center clinical trial of all-trans-retinoic acid, bevacizumab, and atezolizumab in refractory microsatellite stable colorectal cancer.
Authors: Kazmi Syed Mohammad Ali , Al Mutar Salwan , Kainthla Radhika , Jones Amy Little , Abunafeesa Hussna , Hsieh David , Brown Timothy J. , Verma Nilesh
Published: January 2025

TPS324

Background:
A critical clinical challenge in microsatellite stable (MSS) metastatic colorectal (mCRC) patients is to identify strategies to overcome lack of response to immune checkpoint inhibitors. An immunosuppressive tumor microenvironment comprising myeloid-derived suppressor cells (MDSC), endothelial cells, regulatory T cells, tumor associated macrophages, and cancer associated fibroblasts promotes immune evasion and resistance to these agents. MDSCs are bone marrow derived myeloid cells that suppress T-cell function and promote tumor growth. Among all cancers, mCRC patients have one of the highest frequency of MDSC (CD11b+, CD33+, CD14+ HLA-DRneg) in blood (1). It was demonstrated that altering the MDSC% in the tumor microenvironment by ATRA and anti-VEGF therapy (bevacizumab) can enhance the effects of immune checkpoint inhibitors (2-4). The hypothesis of the current clinical trial is that the combination of ATRA, bevacizumab and atezolizumab will lead to a decrease in MDSC population in tumor microenvironment leading to a clinically meaningful improvement in response rates among refractory MSS mCRC patients.
Methods:
This is a single-arm, open-label, phase 2 clinical trial combining ATRA, bevacizumab, and atezolizumab in refractory MSS mCRC patients. It will enroll a total of 21 patients over 24 months at UT Southwestern Medical Center that are MSS by PCR or NGS testing or are proficient in immunohistochemical expression of all four mismatch repair enzymes (MLH1, MSH2, MSH6, PMS2). ATRA will be administered orally at 45 mg/m2/day in 2 divided doses on days 1-7 and repeated every 14 days; atezolizumab will be given intravenously on day 1 at 840 mg dose every 14 days, and bevacizumab will be administered intravenously on day 1 at 10 mg/kg dose every 14 days. The first six patients enrolled on this study will contribute to the safety lead-in phase of this study. The primary outcome is to assess the overall response rate by RECIST v1.1. Secondary outcomes include assessment of disease control rate and frequency of adverse events using CTCAE v5.0. Exploratory outcomes include assessment of PFS and OS and collecting blood and tissue samples at defined timelines to study the changes in the MDSC population among responders and non-responders (NCT05999812). 1. Kobayashi, M. et. al., Clin Cancer Res, 2019. 2. Mirza, N., et al., Cancer Res, 2006. 3. Tobin, R.P., et al., Int Immunopharmacol, 2018. 4. Tobin, R.P., et. al., Clin Can Res, 2023.
Clinical trial information: NCT05999812
.
Elective Discontinuation of Larotrectinib in Pediatric Patients With TRK Fusion Sarcomas and Related Mesenchymal Tumors
Authors: Mascarenhas Leo , DuBois Steven G. , Albert Catherine M. , Bielack Stefan , Orbach Daniel , Federman Noah , Geoerger Birgit , Nagasubramanian Ramamoorthy , Zhang Yizhou , Chisholm Julia , Gallego Melcon Soledad , Goto Hiroaki , Morgenstern Daniel A. , Owens Cormac , Pappo Alberto S. , Perreault Sébastien , Schulte Johannes H. , Shukla Neerav , Zwaan Christian Michel , Neu Natascha , Bernard-Gauthier Vadim , De La Cuesta Esther , van Tilburg Cornelis M. , Laetsch Theodore W.
Published: January 2025

Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor with efficacy in children with TRK fusion tumors. We evaluated patient outcomes after elective discontinuation of larotrectinib in the absence of disease progression in a protocol-defined wait-and-see subset analysis of eligible patients where treatment resumption with larotrectinib was allowed if disease progressed. We also assessed the safety and efficacy of larotrectinib in all pediatric patients with sarcoma. This cohort included 91 patients (younger than 18 years) from two clinical trials: infantile fibrosarcoma (49), other soft tissue sarcomas or related mesenchymal tumors (41), and bone sarcoma (1). Treatment-related adverse events were of maximum grade 1 or 2 in 25% and 25% of patients, respectively. The overall response rate was 87% (95% CI, 78 to 93). In the wait-and-see analysis, 47 patients discontinued larotrectinib. Median time from discontinuation to disease progression was not reached. Sixteen patients had tumor progression during the wait-and-see period. All 16 patients resumed larotrectinib, and 15 (94%) achieved disease control, with 11 objective responses. Larotrectinib continues to demonstrate durable responses with favorable safety in children with TRK fusion sarcomas. Treatment discontinuation is feasible in select patients with objective response and clinical benefit noted in those who have disease progression after elective treatment discontinuation.
Clinical Activity of Mitogen-Activated Protein Kinase Inhibitors in Patients With MAP2K1 (MEK1)-Mutated Metastatic Cancers
Authors: Dankner Matthew , Rousselle Emmanuelle , Petrecca Sarah , Fabi François , Nowakowski Alexander , Lazaratos Anna-Maria , Rajadurai Charles Vincent , Stein Andrew J.B. , Bian David , Tai Peter , Belaiche Alicia , Li Meredith , Quaiattini Andrea , Normanno Nicola , Arcila Maria , Elkrief Arielle , Johnson Douglas B. , Ladanyi Marc , Rose April A.N.
Published: January 2025

PURPOSE

MAP2K1/MEK1 mutations are potentially actionable drivers in cancer. MAP2K1 mutations have been functionally classified into three groups according to their dependency on upstream RAS/RAF signaling. However, the clinical efficacy of mitogen-activated protein kinase (MAPK) pathway inhibitors (MAPKi) for MAP2K1-mutant tumors is not well defined. We sought to characterize the genomic and clinical landscape of MAP2K1 mutant tumors to evaluate the relationship between MAP2K1 mutation class and clinical activity of MAPKi.

METHODS

We interrogated American Association for Cancer Research (AACR) GENIE (v13) to analyze solid tumors with MAP2K1 mutations. We performed a systematic review and meta-analysis of published reports of patients with MAP2K1-mutant cancers treated with MAPKi according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The primary end point was progression-free survival (PFS), and secondary end points were overall treatment response rate (ORR), duration of response (DOR), and overall survival.

RESULTS

In the AACR GENIE data set, class 2 MAP2K1 mutations (63%) were more prevalent than class 1 (24%) and class 3 (13%) mutations (
P
< .0001). Co-occurring MAPK pathway-activating mutations were more likely to occur in class 1 versus class 2 or 3 MAP2K1-mutant tumors (
P
< .0001). Our systematic meta-analysis of the literature identified 46 patients with MAP2K1-mutant tumors who received MAPKi. In these patients, ORR was 28% and median PFS was 3.9 months. ORR did not differ according to MAP2K1 mutation class or cancer type. However, patients with class 2 mutations experienced longer PFS (5.0 months) and DOR (23.8 months) compared with patients with class 1, 3, or unclassified MAP2K1 mutations (PFS 3.5 months,
P
= .04; DOR 4.2 months,
P
= .02).

CONCLUSION

Patients with class 2 MAP2K1 mutations represent a novel subgroup that may derive benefit from MAPKi. Prospective clinical studies with novel MAPKi regimens are warranted in these patients.
Long lived quasinormal modes of regular and extreme black holes
Authors: Skvortsova Milena
Published: January 2025

Recently, black hole models in a nonlinear modification of the Maxwell electrodynamics were suggested, possessing simultaneously properties of an extreme charge and regularity \cite{Bronnikov:2024izh}. We study quasinormal modes of a massive scalar field around such black holes and show that they are characterized by a comparatively small damping rate, indicating the possible existence of arbitrarily long-lived quasinormal modes, called {\it quasi-resonances}.
O-07 RAPIDLY PROGRESSIVE LATE-ONSET X-LINKED ADRENOLEUKODYSTROPHY WITH A NOVEL MUTATION
Authors: Sodan Hulya Nur , Kaya Refika Yorulmaz , Hatipoglu Mustafa , Batur Caglayan Hale Zeynep , Ezgu Fatih Suheyl , Okur Ilyas , Inci Asli , Yegin Zeynep Arzu , Cerit Ethem Turgay , Altinova Alev Eroglu , Toruner Fusun , Karakoc Ayhan , Akturk Mujde , Yalcin Mehmet Muhittin
Published: January 2025

Introduction

X-linked adrenoleukodystrophy (X-ALD; OMIM:300100) is a progressive neurodegenerative disorder resulting from a congenital defect in the ABCD1 gene, which encodes the adrenoleukodystrophy protein (ALDP). Deficiency of ALDP leads to impaired peroxisomal β-oxidation of very long chain fatty acids (VLCFAs), causing their accumulation in the nervous system, testes, and adrenal cortex.

Clinical Case

A 20-year-old male patient was referred to the neurology clinic with a progressive speech disorder, impaired coordination while eating, incoherent speech, prolonged periods of dissociation, and cognitive disability for 6 months. Also clumsiness, unintentional falls, and involuntary arm movements were observed. In fact, when a more detailed history was obtained from the family, they mentioned that the patient had shown signs of clumsiness over the past three years. The patient was born healthy with no underlying health conditions, had an average academic record, and no history of illicit drug use. His neurologic examination did not reveal motor deficits, and the patient was attentive and oriented to person, place, time and situation. However, spasticity was observed in both lower extremities, and it was noted that the patient exhibited difficulty in following commands and doing some movements. His brain MRI revealed bilateral frontoparietal white matter patterns consistent with X-ALD. After that he was referred to our clinic. Adrenal insufficiency was detected, and he was started on hydrocortisone therapy. Elevated very long-chain fatty acid levels were also found. Genetic testing revealed a novel mutation (NM_000033.4 c.778dup p.(Ala260GlyfsTer41) in the ABCD1 gene, which was also detected in the patient’s female sibling. Subsequently, he developed gait disturbances, paraparesis, and sphincter dysfunction. The patient exhibited rapid progression and is currently bedridden, being fed through a percutaneous enteral gastrostomy (PEG) in a three months. According to the evaluation of the patient, it was determined that he was not suitable for gene therapy or stem cell transplant due to the high Loes score (19), rapid progression, and his age.

Conclusion

X-ALD is a rare disease with significant morbidity and a high mortality rate. Typically, affected boys present between four and eight years of age. Our case involves late-onset and rapid progression with a novel mutation.
P-04 A PATIENT WITH A GIANT ADRENAL MASS DETECTED DURING PREGNANCY
Authors: Belten Zeynep Elüstü , Ciftci Sema , Mert Meral , Çakır Ilkay , Kimyon Özge Şahin , Mısıroğlu Fuat , Piskinpasa Hamide
Published: January 2025

Introduction

Although the frequency of adrenal incidentalomas is increasing, they are rarely detected due to lack of imaging during pregnancy. Here, we present a case of adrenal incidentaloma diagnosed during pregnancy.

Clinical Case

A 32-year-old female patient was diagnosed with a mass in the liver during obstetric ultrasonography performed in the 4th month of pregnancy and was referred to gastroenterology clinic for further examination, but any additional intervention could not be made because of patient’s refusion. She underwent an emergent caesarean section at 36th weeks of pregnancy. A mass approximately 15 cm in size, thought to be of adrenal origin, was detected in the retroperitoneal area posterior to the liver at the surgery. Abdominal MRI revealed a 188*121*113 mm non-adenomatous lesion, at right adrenal gland, containing cystic necrotic areas, and not suppressed in fat-suppressed series (figure 1A). At initial assesment by endocrinology, the patient denied any paroxysmal or persistent hypertension, weakness, weight gain and hirsutism. Physical examination was found normal, no signs of Cushing’s syndrome was observed. Laboratory testing including 24-hour urine catecholamines, basal cortisol, dehydroepiandrosterone sulfate (DHEA-S), adrenocorticotropic hormone (ACTH) were in reference ranges. The cortisol levels were supressed following the low-dose dexamethasone test. Adrenal carcinoma was suspected based to radiological features of the lesion. FDG uptake of the mass with a SUVmax: 16.9 was reported at PET-scan (figure 1B). Laparotomy for right adrenal gland was planned, but the patient disapproved once again. She underwent to adrenalectomy 18 months later after the mass was detected. Surprisingly, the pathology resulted as adrenocortical adenoma. Ki67 labeling index was found to be 3-4%, immunohistochemical staining of tissue specimens showed that synaptophysin and chromogranin A negative ( - ), but CD56 positive (++). The patient was lost for approximately 1 year and then aplied to our clinic with another unplanned pregnancy. She is doing well at the 32nd week of her second pregnancy.

Conclusion

Large and non-adenomatous masses detected during pregnancy are likely to be malignant and these masses are usually known with poor-prognosis. Rarely, as seen in our patient, huge adrenal masses may exhibit a benign behavior compatible with an uncomplicated long process despite suspicious radiological imaging features.Figure 1A:Abdominal MRI revealed a 188*121*113 mm non-adenomatous lesion, at right adrenal gland containing cystic necrotic areas. B:Increased uptake of FDG in the right adrenal region (SUVmax: 16.9)
P-11 A CASE OF TUBERCULOSIS ADRENAL INSUFFICIENCY
Authors: Lateef Mustafa Mohamed Abdu , Khudhair Mahmood Shakir
Published: January 2025

Introduction

Adrenal tuberculosis is rare form of extrapulmonary tuberculosis, and may cause to primary adrenal insufficiency. This report presents a case of middle age male diagnosed with adrenal tuberculosis.

Tuberculosis is a major health concern worldwide. The extrapulmonary manifestations account for 5% to 15% of all cases, although adrenal tuberculosis is uncommon, it can lead to primary adrenal insufficiency and has diagnostic challenges due to its nonspecific presentation. Pulmonary Tuberculosis is still common in Iraq, although no case reports exit up to our knowledge of adrenal Tuberculosis.

Clinical Case

40-year-old man, sanitation worker, presents with 3 months history of significant weight loss and fever with night sweating. He complains of nausea, occasional vomiting, fatigue, unintentional weight loss of approximately 12 kg, decreased appetite, abdominal pain and joint pain. He also reports skin hyperpigmentation particularly in the hand creases, mouth and mucous membranes of the lips. There are no respiratory symptoms such as shortness of breath or cough. The past medical history is unremarkable. There is positive family history of pulmonary tuberculosis (grandmother). He does not smoke or drink alcohol.

Physical examination reveals ill-looking malnourished patient, with BP of 100/60 with postural hypotension, PR of 80 bpm and RR of 24/min. There is diffuse hyperpigmentation particularly noted in palmer creases and oral cavity. The other system examinations are normal.

Laboratory investigations revealed mild normochromic normocytic anemia (Hb 11.4), and mild lymphocytosis, Na 126 mEq/l, k 4.1 mEq/l, FBS 87 mg/dl, high ESR, mild elevation of TSB 1.8 mg/dl normal renal function, morning cortisol of 0.75 Mcg/dl and morning ACTH of 1808 pg/ml.

Imaging studies show a normal chest X-ray. Abdominal CT reveals bilateral adrenal enlargement in size with lobulated irregular contours and heterogeneous density exhibiting foci of calcification and central cystic/necrotic non-enhancing centers, with predominantly peripheral enhancement seen on the contrast scan. The mean density of the solid parts of the glands is around 30-40 HU on the native scan, the right adrenal measures 2.7x1.7x2.7 cm, the left adrenal measures 5.6x3.2x2.5 cm. IGRA test is positive. Adrenal biopsy was not performed because the presentation was highly suggestive of adrenal tuberculosis.The diagnosis was primary adrenal insufficiency due to adrenal tuberculosis Anti TB drugs were initiated on standard regimen of INH, Rifampicin, Pyrazinamide, and Ethambutol. Hydrocortisone replacement was initiated. The patient required higher dose of hydrocortisone (20 mg in the morning, 10 mg at 6 pm) which could be due to CYP 3A4 induction by rifampicin Fludrocortisone 0.1mg daily was also started. The patient’s symptoms improve dramatically after initiation of treatments, with gradual increase in body weight.Figure 1:Hyperpigmentation of the patient hands
P-30 ROLE OF PLASMAPHERESIS IN TREATING A RARE CASE OF EXOGENOUS INSULIN ANTIBODY SYNDROME (EIAS) IN A YOUNG PATIENT WITH TYPE 1 DIABETES MELLITUS IN BABYLON GOVERNORATE: A CASE REPORT
Authors: Alsaffar Yassamin Riyadh , Algburi Saif Mohammed
Published: January 2025

Clinical Case 

A 17-year old female patient who was diagnosed with type 1 diabetes mellitus (DM) seven years ago, and she had continuously very high blood glucose readings with recurrent admissions to the emergency unit due to attacks of DKA. In addition to a planned diet, she was on more than 250 units of insulin per day (while her weight was 75 kilograms). She was initially on human insulin in the form of twice NPH insulin injections, and pre-meal regular insulin injections, in addition to repeated regular insulin correction doses without any reduction of her blood glucose. Then she was shifted to insulin analogues (to eliminate the possibility of insulin immunogenicity which have been encountered with the use of human insulin), in form of basal insulin Glargine OD, plus pre-meal rapid acting insulin Glulisine without any noticeable response. Continuous switching of her injection sites, with an in-hospital observed insulin injections (to avoid noncompliance), even the use of intravenous route did not help to achieve a glycemic control. Later on, metformin 1000 mg XR BID was added to her daily treatment without any benefit. A screen of anti-insulin antibodies was done and found to be elevated (which should be negative after all these years after her initial diabetes diagnosis). A presumptive diagnosis of EIAS (Exogenous Insulin Antibody Syndrome) was put. A small dose of steroids was administered with close observation (to avoid exacerbation ketosis) without any improvement. Then Cellcept (Mycophenolate mofetil), an immune modulator was added at a dose of 500 mg BID and increased 48 hrs. later to 1000 mg BID and resulted in a minimal reduction of her blood glucose levels. Finally the decision of plasmapheresis was made and an informed consent was obtained from the family after explaining the condition. A good response was recorded after the 1st session, with a minimal decrease of her total daily insulin doses. Later on, an additional excellent response was received during the next 2 sessions with a rapid decline of her glucose readings and her total daily insulin doses. She had recurrent attacks of hypoglycemia during her third and last plasmapheresis session. Her total daily dose of insulin was successfully reduced by more than 50%, and her general condition was improved noticeably without any recorded adverse reactions, as shown in the blood glucose logbook photos attached below.Figure 1:Glucose logbook after the 3rd and last session of Plasmapheresis  Table 1:Response parameters to three sessions plasampheresis therapy
P-51 A RARE CASE IN WHICH ACROMEGALY IS PROVEN CLINICALLY AND BIOCHEMICALLY DESPITE NEGATIVE GH IMMUNOHISTOCHEMICAL STAINING
Authors: Özışık Hatice , Ünal Kocabaş Gökçen , Ulaş Ezgi , Ertan Yesim , Biçeroğlu Hüseyin , Yürekli Banu Sarer , Yarman Sema
Published: January 2025

Introduction

The diagnosis of acromegaly is confirmed by high IGF-1 and GH levels. When a GH-secreting pitNET is resected, immunocytochemistry with GH staining typically supports the diagnosis. It is very rare for these tumors to stain negatively for GH in the presence of clinical and biochemical acromegaly. We are presenting a case of growth hormone (GH)-secreting PitNET with negative immunostaining for GH.

Clinical Case

50-year-old male with history of headache and visual disturbances was found to have a pituitary macroadenoma. Years before the presentation, he noticed his shoe size had increased. Physical exam was notable for enlarged nose, thick lips, mandibular prognathism, and enlarged hands and feet. Blood pressure was 140/90 mmHg. Pre-operative laboratory results were remarkable for elevated GH 5.6 ng/ml (0.03-2.47) and IGF-1 816 ng/ml (80.6-207) levels. OGTT suppressed GH nadir 3.95 ng/ml. Pituitary MRI revealed an invasive macroadenoma measuring 37x31x40 mm (Figure 1). The patient underwent transsphenoidal surgery. Although GH and IGF-1 levels decreased after surgery, they did not return to the normal range. Visual field loss improved. Surprisingly, in the histopathological examination, no immunohistochemical staining was detected with GH and other anterior pituitary hormones, and Ki-67 was found to be 2%. Due to disease activity (IGF-1:278 ng/ml; 1.3XULN), medical treatment was started first with dopamine agonist and then continued with somatostatin receptor agonist (IGF-1:322 (1.6xULN). The remaining tumor tissue remained stable under treatment.

Conclusion

Silent somatotrophinomas detected by immunohistochemical staining have been reported in the literature. Conversely, endocrinologists should keep in mind that there may be rare cases in which immunohistochemical GH staining is negative but clinical and hormonal acromegaly is evidenced.Figure 1Magnetic resonance imaging (MRI) revealed a pituitary macroadenoma 37x31x40 mm in size, with Knosp grade 4 on the right and grade 1 on the left
P-52 ASYMPTOMATIC MIXED PITUITARY MACROADENOMA IN A YOUNG MALE PATIENT
Authors: Omma Tülay , Imge Aydoğan Berna , Emmez Hakan , Cesur Mustafa
Published: January 2025

Introduction

Central hyperthyroidism due to a thyrotropin (TSH)-secreting pituitary adenoma is a rare cause of hyperthyroidism, representing 0.5-1.0% of all pituitary adenomas. The etiopathogenesis of TSH-secreting-adenomas is unknown and no definite role for various oncogenes has been proven. Plurihormonal pituitary adenomas reveal greater tumor recurrence and local invasion than do mono-secreting pituitary adenomas and therefore they need to be followed more closely.

Clinical Case

We present the case of a 19-year-old male who was admitted to the endocrinology clinic, was asymptomatic, and had abnormal thyroid tests during routine examinations. Laboratory tests revealed TSH 1.33 (normal RI), freeT4 2.5 (high), freeT3 6.78 (high), and the patient had tachycardia (pulse 120/min) on physical examination, but had no complaints. Thyroid antibody tests were negative, and ultrasonography revealed normal thyroid gland size and homogeneous parenchyma. Alpha subunit test was requested with suspicion of TSHoma and genetic test was requested considering thyroid hormone receptor resistance. In the pituitary panel tests, the patient's GH and IGF1 tests were found to be high for his age and gender, The lowest GH value in the GH-OGTT test was 3.95 ng/mL. LH was high but testosterone was within the normal reference range. The patient was found to have mandibular prognathism and his secondary sex characteristics were normal. Pituitary MRI revealed a nodular appearance on the left side of the pituitary gland, measuring 13x9 mm, hypointense on T1A, hyperintense on T2A, and showing contrast medium uptake. The infundibulum deviates to the right, and there is no pressure on the optic chiasm. Visual field test was normal. AlphaSubunit pituitary tumor marker value was found to be high at 1.9ng/mL (RIs ≤0.5). The genetic test for resistance to thyroid hormone, also came back normal. The patient underwent endoscopic transsphenoidal pituitary adenomectomy due to pituitary macroadenoma by an experienced neurosurgeon. No postoperative complications developed. In cytopathological evaluation, histochemical studies performed with silver stain showed that the reticulin roof was lost. In immunohistochemical studies, SF-1, PIT-1, LH (diffuse), GH (densely granular), TSH (rare) and LMWK (perinuclear cytoplasmic weighted) were positive. T-PIT and Prolactin were negative. Ki-67 proliferation index was 5%. Postoperative pituitary tests were normal and no deficiency was observed and no treatment was required. At the postoperative 3rd month follow-up, the lowest GH value in the GH-OGTT test was 0.16 ng/mL, and no residual mass was observed in the pituitary MRI. The patient, who had no postoperative complaints, is being followed up by the endocrinology clinic.

Conclusion

Mixed pituitary tumors are rare and can sometimes appear as silent tumors, but may be aggressive during follow-up, so better follow-up is necessary.Table 1:Pituitary panel biochemical results
P-53 PITUITARY STALK INTERRUPTION SYNDROME: A CASE REPORT
Authors: Rıza Baykal Gokhan , Keskin Müge , Yazgan Pınar , Aydın Cevdet , Topaloğlu Oya , Ersoy Reyhan , Çakır Bekir
Published: January 2025

Introduction

Pituitary stalk interruption syndrome (PSIS) is a congenital abnormality of the pituitary gland responsible for GH deficiency or global pituitary insufficiency and is usually characterized by the triad of a very thin or interrupted pituitary stalk, an ectopic (or absent) posterior pituitary (EPP), and hypoplasia or aplasia of the anterior pituitary visible on magnetic resonance imaging (MRI). The etiology of this syndrome is not fully understood, and many theories, like perinatal injuries or defective organogenesis due to genetic or environmental factors during pregnancy, are proposed. In family cases of PSIS, rare mutations of HESX1, LH4, OTX3, SOX3 and PROKR2 may be the cause. In the majority of cases, no genetic cause is found. The symptoms and signs of this syndrome typically become apparent in the neonatal period and childhood. Sometimes symptoms can be overlooked, and diagnosis can be delayed.

Clinical Case

A 22-year-old male presented in our clinic with hypothyroidism and growth hormone deficiency. He had previously received growth hormone (GH) treatment for 6 years until he was 15 years old. He was receiving levothyroxine therapy for hypothyroidism. Complete blood count, serum electrolytes, erythrocyte sedimentation rate, urinalysis, and thyroid function tests were normal. Hormonal analysis showed FSH: 11.9 U/L (N = 1.4-18.1 U/L), LH: 4.1 U/L (N = 1.5-9.3 U/L), prolactin: 9.1 μg/L (N = 5.4-15.4 μg/L), ACTH: 24.5 pg/mL (N = <46), fasting morning cortisol: 17.2 μg/dL (N = 5.2-22.4 μg/dL), total testosterone: 4.03 μg/L (N = 1.64-7.53 μg/L), free testosterone: 6.39 pg/mL (N = 5.4-40 pg/mL), IGF-1: 114 μg/dL (N = 161-384 μg/dL). Brain MRI revealed slightly hypoplastic sella turcica and adenohypophysis measuring 4.2 mm in height, thin infundibulum, and ectopic posterior pituitary located posterior to the infundibulum in the suprasellar cistern. The diagnosis of pituitary stalk interruption syndrome is mainly based on its clinical manifestations, laboratory tests, and imaging examinations.

Conclusion

PSIS is a rare congenital malformation that presents with significant growth and developmental challenges in children. The symptoms can be disregarded, and the diagnosis will therefore be delayed. Early diagnosis and treatment are crucial for improving growth outcomes and overall quality of life. It must be considered in the presence of combined or isolated hypopituitarism. MRI is the imaging modality of choice for the diagnosis of this condition. Regular monitoring and supportive care are essential components of effective management for these patients.
Can Family Policies Enhance Fertility? An Ex Ante Evaluation Through Factorial Survey Experiments
Authors: Guetto Raffaele , Alderotti Giammarco , Vignoli Daniele
Published: January 2025

This article explores the family policies–fertility nexus by assessing the potential impact of parental leaves, childcare services, and child benefits on fertility through a factorial survey experiment (FSE). We focus on Italy, where persistently low fertility rates are often linked to limited welfare support for families. We surveyed 4,022 respondents aged 20–44 and exposed them to various scenarios characterized by different family policy packages. We asked them to ascribe short-term fertility behavior to a fictitious couple under each scenario. Results show that each family-friendly policy envisioned positively impacts ascribed fertility. The availability of full-time, public childcare services seems more relevant than higher child benefits, whereas more generous and gender-equal parental leaves are perceived as less relevant. However, results suggest that only a consistent mix of financial benefits, parental leave schemes, and childcare provisions can boost fertility. In contrast, marginal changes in single policy levers are most likely ineffective. The FSE reveals that a couple's socioeconomic status is perceived as more important than family policies for fertility: ascribed fertility increases when both partners are employed and household income is high. We conclude by discussing the policy implications of our findings.
Stratified Impact of Therapies on Anaplastic Thyroid Cancer Outcomes in the Pre-Gene-Targeted Therapy Era
Authors: Zhang Kun , Wang Xinyi , Lei Jianyong , Su Anping , Wei Tao , Li Zhihui , Chen Ya-Wen
Published: January 2025

Background

Anaplastic thyroid cancer (ATC) is a highly lethal disease, often diagnosed with advanced locoregional and distant metastases, resulting in a median survival of just 3–5 months. This study determines the stratified effectiveness of baseline treatments in all combinations, enabling precise prognoses prediction and establishing benchmarks for advanced therapeutic options.

Methods

The study extracted a cohort of pathologically confirmed ATC patients from the Surveillance, Epidemiology, and End Results program. Overall, 1879 patients from 2000 to 2018 were identified from the database. Kaplan–Meier survival curve estimation and Cox proportional hazard regression were applied.

Results

Overall, compared with no treatment, surgery raised 1-year overall survival (OS) from 0.6% to 30% and median survival from <1 month to 3 months in ATC patients. For stage IVa, surgery increased 1-year OS from 21.5% to 71.8% and median survival from 2 to 23.5 months, and in stage IVb, surgery increased 1-year OS from 9.4% to 41.3% and median survival from 2 to 7 months; however, in stage IVc, the benefits of surgery were not markedly different from non-surgical approaches. When combined with surgery, other effective non-surgical ATC treatments demonstrated a surgery-dominant synergistic effect, particularly for stages IVa and IVb ATC, but not for stage IVc ATC.

Conclusions

Our study provides insights into stratified baseline treatments for patients with ATC in all stages, emphasizing surgery’s vital role in a multimodal approach.
A Digital Twin Framework for Nuclear Power Equipment Maintenance: Design, Prototyping, and Preliminary Validation
Authors: Xu Qingfeng , Zhou Guanghui , Zhang Chao , Chang Fengtian , Huang Qian , Zhang Min , Zhi Yifan
Published: January 2025

Throughout the lifecycle of Nuclear Power Equipment (NPE), maintaining high-safety maintenance services is essential for optimal operation. Traditional time-based maintenance strategies are limited in NPE contexts due to stringent safety requirements and high costs of complex systems. Specifically, maintenance processes lack transparency, state monitoring relies heavily on manual inspections, and decisions depend passively on individual expertise. Digital Twin (DT) effectively breaks down "information silos," leverages data value, and enables proactive maintenance decision-making for NPE. However, DT application in the nuclear industry is still exploratory, with limited systematic and practical research, especially for critical equipment maintenance. This paper introduces a DT-based intelligent maintenance decision system featuring three key technologies: DT modeling, state monitoring with dynamic early warning, and systematic intelligent decision-making and verification. A DT-based prototype using a cooling water pump case study preliminarily validates the state monitoring model's accuracy. Results indicate that the proposed framework and methods are feasible and hold significant application potential.
Waveform characteristics in thoracic paravertebral space: a prospective observational study
Authors: Vijitpavan Amorn , Termpornlert Sivaporn , Subsoontorn Pattika , Vareesunthorn Lalinthip
Published: January 2025

Background With increased use of thoracic paravertebral block (TPVB) in thoracic surgery, many faced the challenge of locating the thoracic paravertebral space (TPVS) ultrasonographically. This observational study aimed to investigate the waveform characteristics and pressure value within the TPVS in anaesthetized patients with controlled ventilation. Methods 50 patients scheduled for elective lung surgery were enrolled. After conduction of anesthesia, all patients underwent TPVB at T4/5 and T6/7 using transverse, in-plane ultrasound guidance. A pressure transducer system with a desktop monitor was connected to the needle hub to measure pressure values and waveform characteristics in three locations: the paraspinal muscles, immediately behind the superior costotransverse ligament, and within the TPVS. Next, 15 mL of 0.33% bupivacaine was injected into each desired TPVS. After completion of the surgery, the extent of dermatomal blockade and the pain score was assessed in all patients. Results 98 typical regular respiratory waveforms with a mean pressure of ≤ 25 mmHg were detected in the TPVS of 50 patients. The sensitivity of the combined ultrasound and pressure waveform measurement technique to identify the TPVS was 95.45% (95% confidence interval, 84.527–99.445). Nontypical respiratory waveforms were present in two patients. Factors interfering with the TPVS waveform characteristics were previous thoracic surgery. Conclusion The TPVS had low pressure and showed a smooth, regular waveform pattern corresponding to respiration.
Impact of distress and anxiety due to COVID-19 on digital addictions in university students in the third wave period
Authors: Capa-Luque Walter , Mayorga-Falcón Luz Elizabeth , Barboza-Navarro Evelyn , Martínez-Portillo Armando , Pardavé-Livia Yovana , Hervias-Guerra Edmundo , Bazán-Ramírez Aldo , Bello-Vidal Catalina
Published: January 2025

Abstract Background Digital addictions are a major problem worldwide, which has increased considerably during the COVID-19 pandemic. In this scenario, two important impact factors to explain this problem are stress and anxiety because of COVID-19. The objective of this research was to determine the impact of distress and anxiety due to COVID-19 on digital addictions. Methods cross-sectional, explanatory study. A total of 802 students from public and private universities residing in the city of Lima and Callao (Peru), with a mean age of 21.68 (SD = 3.11), selected by convenience sampling, participated in the study. The MULTICAGE CAD-4 questionnaire, the distress scale, and the anxiety scale by COVID-19 were applied. Results two models examined with structural equation modeling showed good fit indices (CFI and TLI > .95, RMSEA and SRMR < .06). The first model shows that the latent variables distress and anxiety due to COVID-19 have direct effects on digital addictions as a general construct (R2 = 22%). The second model shows that the exogenous latent variables (stress and anxiety) have direct effects of different magnitudes on each digital technology, so the variance explained on smartphone addiction was higher (R2 = 25%) with respect to internet (R2 = 19%) and video game addiction (R2 = 6%). It was also found that for every male, there are two females with high levels of distress and anxiety. Regarding the problematic use of smartphones and internet, there is a prevalence of 40% regardless of sex; but as for the problematic use of video games, there is a marked difference between males (18.8%) and females (2.7%). Conclusion the distress and anxiety caused by COVID-19 have a direct impact in aggravating digital addictions.