Therapeutic Challenge Research Articles

Surgical treatment of invasive pulmonary fungal infections in immunocompromised pediatric patients: Aspergillus spp. and other emerging fungi.

Invasive Pulmonary Fungal Infections (IPFIs) represent a diagnostic and therapeutic challenge. The exact role of surgery is not well defined. This study analyzes our experience with surgical treatment of IPFI in immunocompromised pediatric patients and, secondarily, compares IPFI caused by Aspergillus spp. with other fungal infections. This is a retrospective review (2000-2019) of patients with IPFI surgically treated at our pediatric institution. Statistical analysis was used to compare data between Aspergillus spp. and non-Aspergillus IPFI. Twenty-five patients (64% female) underwent 29 lung resections. Median age at surgery was 7.19years (1.63-19.14). The most frequent underlying condition (64%) was acute leukemia. Surgical indications included persistence or worsening of symptoms and pathological image findings (52%) or asymptomatic suspicious lesions in patients scheduled for intensive cytotoxic treatments or hematopoietic stem cell transplantation (48%). All patients underwent atypical lung resections, except one lobectomy. Aspergillus spp. was the most frequently isolated pathogen (68%). Follow-up was 4.07years (0.07-18.07). Surgery-related mortality was 0%, but 4 patients died in the 100days following surgery (2 due to disseminated fungal infection); the remaining 21 did not show signs of IPFI recurrence. Non-specific consolidations on CT scan were more frequent in non-Aspergillus IPFI (p < 0.05). Surgical treatment of IPFI should be considered as a part of the treatment in selected pediatric immunocompromised patients, and it may have both diagnostic and therapeutic advantages over non-surgical management. When there is clinical suspicion of IPFI but CT scan shows unspecific alterations, the possibility of a non-Aspergillus IPFI should be considered.

8227 Complex Case of Myxedema Coma Complicated by Cardiac Arrest in a Geriatric Patient with Multiple Comorbidities

Abstract Disclosure: M. Parvez: None. L. Makahleh: None. S. Nagpal: None. A. Kavarthapu: None. V. Vedantam: None. Introduction: This case report details a rare instance of cardiac arrest in a patient with myxedema coma, a severe form of hypothyroidism. It highlights the diagnostic and therapeutic challenges in managing such complex endocrine emergencies. Case Presentation: A 70-year-old female with a history of hypothyroidism, type 2 diabetes, atrial fibrillation, pacemaker implantation, and COPD presented with a 3 day history of progressive lethargy and weakness. EMS found her with critically low blood glucose level of 20. History and Examination revealed non-compliance with thyroid medication and myxedematous features including moon-like facies, periorbital edema, generalized edema, elevated JVP, and cold extremities with sluggish capillary refill. In the ER, she was hypotensive, labs showed a significantly elevated TSH level of 30.55 (0.45-4.5), free T3 level of 1.2 (2.3-4.2), free T4 level of 1.12 (0.93-1.70), high lactate, metabolic acidosis, renal impairment, and liver enzyme elevation. These findings, coupled with the clinical presentation, led to the diagnosis of myxedema coma. The patient's critical state was further complicated by distributive shock, shock liver and oliguric AKI. Management included sodium bicarbonate infusion for severe acidosis, IV hydrocortisone, IV levothyroxine, and broad-spectrum antibiotics. Amiodarone was discontinued due to its potential contribution to acute liver injury and hypothyroidism. Despite interventions, she developed acute respiratory failure, requiring intubation and norepinephrine for low mean arterial pressure. Her renal function improved with pressor support, and her lactic acidosis resolved. She recovered quickly and was subsequently extubated. After stabilization, she was switched to oral levothyroxine and discharged. Shortly after discharge, she returned again with generalized weakness, confusion, and dysuria. ER evaluation revealed lethargy, hypotension, hypoglycemia, severe metabolic acidosis, and a UTI. She tested positive for Influenza. While in the ER, she had cardiac arrest, presenting with agonal breathing and PEA. CPR was initiated, achieving ROSC after two rounds and one dose of epinephrine. She was treated again with IV levothyroxine, and IV antibiotics. She recovered well and was discharged to rehab facility with re-education on compliance. Conclusion: This case exemplifies the complexity and challenges in managing a geriatric patient with multiple comorbidities, particularly in the context of myxedema coma. The intricate interplay of endocrine, cardiovascular, respiratory, and infectious complications necessitated a multifaceted and dynamic therapeutic approach. This case underscores the importance of compliance, vigilant monitoring, prompt recognition of complicating factors, and the need for a coordinated multidisciplinary approach in managing similar cases. Presentation: 6/2/2024

7883 Atypical Presentation of Macroprolactinoma: Discordantly Low Serum Prolactin and Therapeutic Challenges

Abstract Disclosure: S. Hossain: None. M.S. Hossain: None. B. Gautam: None. S.C. Kumar: None. H. Liao: None. D.S. Rosenthal: None. Introduction: Pituitary tumors are categorized as microadenomas (&amp;lt;1 cm) and macroadenomas (&amp;gt;1 cm) with prolactinomas being one of the most common causes. The mean prevalence of prolactinomas is 10 per 100,000 in men and 30 per 100,000 in women. Serum prolactin levels corresponds to the size of the prolactinoma and any discrepancy should be treated with caution as that may indicate co-existence of pluripotent cells. We present a patient who presented with visual field defect and headaches, found to have a pituitary macroadenoma with discordantly low serum prolactin level compared to the size of adenoma, prompting a change in the treatment course. Case Presentation: A 42 year old male with no past medical history was seen as an endocrinology consult requested by neurosurgery for frequent headaches and visual problems for 1 year. Vital signs were normal, with negative orthostatic drop of blood pressure. He had prominent bitemporal hemianopsia confirmed by formal visual field testing by Ophthalmology. No galactorrhea or features suggestive of acromegaly or hyperthyroidism. He complained of erectile dysfunction but appeared to have normal male secondary sexual characteristics. MRI of brain showed a suprasellar mass measuring 3.8 x 2.6 x 2.2 cm with mass effect on the optic chiasm, hypothalamus with extension and infiltration into the right cavernous sinus. Lab results showed elevated prolactin of 1343.5 ng/ml confirmed by serial dilution, low serum testosterone level of 134 ng/dl and inappropriately normal FSH and LH. Complete blood counts, comprehensive metabolic panel, TFT, ACTH, cortisol and IGF-1 were normal. Patient was started on bromocriptine and he noticed improvement in his field of vision and acuity within one week of starting therapy. He continued to show sustained improvement in vision and resolution of his headaches at the one-month mark. MRI 2 months from starting bromocriptine showed modest reduction in size of the tumor to 2.1 x 2.3 x 2.4 cm with continued mass effect on the optic chiasm. Prolactin level decreased to 69.3 ng/ml. Therefore, although there was some improvement in visual fields, surgical resection was recommended to alleviate the mass effect on the optic chiasm. Conclusion: Our case highlights the significance of identifying discrepancies between the size of a prolactinoma and serum prolactin levels. Expected prolactin level from a prolactinoma similar in size to our case would be &amp;gt;3000 ng/ml when ours was 1343.5ng/ml. Despite undergoing treatment and lowering of prolactin levels our patient's pituitary adenoma did not significantly reduce in size after two months of treatment with bromocriptine and the mass continued to exert pressure on the optic chiasm. This suggests possible presence of pluripotent cells in addition to prolactin-producing cells within the tumor. The recommended course of action was surgical resection of the mass. Presentation: 6/1/2024

7752 Navigating Hypercalcemia in Pregnancy: A Case Report

Abstract Disclosure: J. Gabbay: None. S. Steinmetz-Wood: None. Introduction: Primary hyperparathyroidism (PHPT) in pregnancy is rare but presents many diagnostic and therapeutic challenges. Prompt diagnosis and treatment are important due to associated maternal and fetal risks, however evaluation of urine calcium to differentiate from Familial Hypocalciuric Hypercalcemia (FHH) becomes less reliable due to physiologic changes in pregnancy, sestamibi scans. CT scans require radiation, parathyroidectomy introduces surgical risk, and medical alternatives like bisphosphonates can interfere with fetal skeletal development. Clinical Case: A 24-year-old woman who presented to the emergency room for progressive nausea and abdominal pain was found to be pregnant with elevated serum calculated calcium to 11.4 mg/dL (2.84 mmol/L). She had a history of renal stones, longstanding hypercalcemia of unknown etiology and a remote family history of parathyroid “issues”. Follow up laboratory work showed a PTH of 75.8 pg/ml (8.04 pmol/L) with an elevated 24-hour urine calcium and a low 25OH vitamin D. Given her history of kidney stones and overt symptoms it was our clinical judgement that this was not a case of FHH. She was started on IV fluids twice weekly. After an unrevealing neck ultrasound, an MRI neck showed a 7 mm lesion along the posterior aspect of the left thyroid suggestive of a parathyroid adenoma. Sestamibi scan was avoided due to the risks of radiation to the developing fetus. Given the presumptive diagnosis of parathyroid adenoma, the lack of response to aggressive hydration, and the maternal and fetal risks of hypercalcemia during pregnancy, parathyroidectomy was pursued in her second trimester. Intra-operative inspection and biopsy showed the lesion to be only a lymph node. She underwent 4-gland exploration and the left inferior parathyroid gland, which appeared abnormal and enlarged, was removed. The intra-operative PTH dropped only from 98 to 80 (10.4 to 8.5 pmol/L). She otherwise had an unremarkable hospital course and at discharge her calcium was normal with an undetectable PTH, which can be an expected finding in pregnancy. On follow up she was feeling well with sustained normocalcemia and low PTH levels. Given the age at which her hyperparathyroidism started, she was referred to genetics for further evaluation. Clinical Lessons/Conclusion: There were significant biochemical and radiological limitations in the management of this case. Normally an inappropriately normal PTH with elevated serum calcium and normal urine calcium/creatinine clearance ratio confirms the diagnosis of PHPT, however in pregnancy it should be noted that FHH could also present with normal or elevated urine calcium due to absorptive hypercalciuria in pregnancy. Additional clinical history and reasoning was needed for management as well as a skilled surgeon, where preoperative localization was limited and was not ultimately helpful. Presentation: 6/2/2024

8063 Cystic Parathyroid Adenoma: A Rare Cause Of Severe Hypercalcemia

Abstract Disclosure: M. Owrangi: None. F. Hasan: None. Introduction: Parathyroid adenomas are the most common cause of primary hyperparathyroidism, but within this category, a rare subtype exists - cystic parathyroid adenomas (CPAs). Comprising only 0.5-1% of all parathyroid lesions, CPAs present unique diagnostic and therapeutic challenges. We report a case of a female patient presenting with severe hypercalcemia caused by a CPA. Case presentation: A 44-year-old African American female with a history of nephrolithiasis presented with abdominal pain and signs of dehydration. Labs were remarkable for serum calcium 13.2 mg/dL, albumin 4.0 g/dL, phosphorus 1.8 mg/dL, iPTH 617.7 pg/mL, 25-OH vit D 12.1 ng/mL, creatinine 0.85 mg/dL. She was initially resuscitated aggressively with IV fluids resulting in an improvement in serum calcium level to 10.3 mg/dL. Thyroid US showed a cystic nodule deep to the left thyroid lobe. Sestamibi parathyroid scan was consistent with a left superior parathyroid adenoma. She underwent 2 gland parathyroidectomy 3 months after the initial presentation. Intraoperatively serum PTH decreased by 91% after resection of the 2 parathyroid adenomas. Pathology confirmed the presence of 2 parathyroid adenomas, the larger one measuring 2.8 cm and weighing 3.8 g. Discussion: We describe a case of a middle-aged female presenting with severe hypercalcemia due to CPA. Her initial presentation was concerning for parathyroid carcinoma given the severity of hypercalcemia. However, the radiologic findings, coupled with surgical pathology, indicated that she had CPA. CPAs can be either functional, causing primary hyperparathyroidism (PHPT) with elevated serum calcium levels, or non-functional, remaining asymptomatic. Clinical features of PHPT associated with CPAs are similar to those with solid adenomas and include fatigue, GI symptoms, nephrolithiasis, bone pain, and neuropsychiatric manifestations. However, CPAs may exhibit certain distinct presentations: i) higher pre-operative serum calcium levels; and ii) increased risk of symptomatic hypercalcemia. Despite their rarity, CPAs deserve special attention due to their unique presentation, challenging diagnosis, and potential for severe hypercalcemia. Surgical parathyroidectomy is the definitive treatment for functional CPAs. Accurate localization and complete excision of the adenoma are crucial to avoid recurrence. Most CPAs occur in the fourth and fifth decade of life and are more common in women (female to male ratio of 2.5:1). 65-85% of cases are located in the neck and the majority arise from the inferior parathyroid glands and are left-sided, and may very rarely be intrathyroidal. Presentation: 6/2/2024

The role of 1q abnormalities in multiple myeloma: Genomic insights, clinical implications, and therapeutic challenges

Chromosome 1q copy number variations, collectively termed +1q, are 1 of the most common cytogenetic abnormalities in multiple myeloma. 1q abnormalities are associated with overexpression of a high-risk gene signature promoting cell proliferation, apoptosis resistance, genomic instability, and treatment resistance, and acquisition or expansion of +1q subclones mediate disease development and relapse. While there remains significant controversy as to whether the presence of +1q is itself an independent driver of poor prognosis or is simply a marker of other high-risk features, +1q has recently been incorporated into multiple prognostic scoring models as a new high-risk cytogenetic abnormality. In this review, we present possible underlying genetic mechanisms of high-risk disease in +1q myeloma, implications for subclonal development, its role in modifying the tumor microenvironment, current evidence for clinical significance in newly-diagnosed and relapsed patients, and current controversies in +1q classification and prognostication.

Pharmacological targeting of P300/CBP reveals EWS::FLI1-mediated senescence evasion in Ewing sarcoma

Ewing sarcoma (ES) poses a significant therapeutic challenge due to the difficulty in targeting its main oncodriver, EWS::FLI1. We show that pharmacological targeting of the EWS::FLI1 transcriptional complex via inhibition of P300/CBP drives a global transcriptional outcome similar to direct knockdown of EWS::FLI1, and furthermore yields prognostic risk factors for ES patient outcome. We find that EWS::FLI1 upregulates LMNB1 via repetitive GGAA motif recognition and acetylation codes in ES cells and EWS::FLI1-permissive mesenchymal stem cells, which when reversed by P300 inhibition leads to senescence of ES cells. P300-inhibited senescent ES cells can then be eliminated by senolytics targeting the PI3K signaling pathway. The vulnerability of ES cells to this combination therapy suggests an appealing synergistic strategy for future therapeutic exploration.

8282 A Diagnostically Challenging Case of Ectopic ACTH Secreting Pancreatic Neuroendocrine Tumor Presenting with Cushing’s Syndrome

Abstract Disclosure: O.A. Aluko: None. S. Patel: None. S.V. Silparshetty: None. T. Gallagher: None. Introduction: Ectopic ACTH mediated Cushing’s syndrome is an uncommon but treatable condition that poses time constrained diagnostic and therapeutic challenge due to severe morbidity as illustrated by our case below. Clinical case:A 65-year-old male was admitted with profound generalized weakness. He became restricted to wheelchair from being able to hike a trail at Yosemite national park 8 weeks prior. Recent history included hospitalization with uncontrolled diabetes and hypertension, new vertebral compression fractures, AKI, hypokalemia, proximal myopathy, anasarca, upper GI bleed and acute upper extremity DVT. Initial testing there revealed hypercortisolemia, elevated ACTH and a normal pituitary MRI. Further workup at our center revealed elevated 24hr urinary cortisol 2598 (n = 5 - 64 μg/24hr), random cortisol 55 (n= 4.2 -22.4 μg/dL) with elevated ACTH 194 (n= 7.2 - 63.3 pg/mL) consistent with ACTH dependent hypercortisolism. IPSS deferred due to AKI, underlying comorbidities and severe cervical stenosis with myelopathy. ACTH and cortisol remained elevated with an 8mg dexamethasone suppression test suggesting ectopic source ACTH. CT with contrast of chest, abdomen and pelvis showed 5mm right lower lobe lung nodule and bilateral adrenal nodularity. Bronchoscopic FNAC was negative for NET.Ketoconazole 400 mg twice daily was started pending localization of culprit lesion with improvement in 24 hr urinary cortisol to 554μg/24 hr however this was stopped within 4 weeks due to acute transaminasemia. Repeat imaging with Gallium-68 dotatate PET CT showed a 1.8 X 2.4 X 1.7 cm pancreatic mass. He underwent distal pancreatectomy with splenectomy. Pathology confirmed a 2.2cm well differentiated neuroendocrine tumor limited to the pancreas with immunohistochemistry strongly for ACTH and weakly for Gastrin. Postoperatively, patient was given hydrocortisone replacement. ACTH was 14.3 pg/mL and cortisol 6.2μg/dL a few weeks later. His diabetes, hypertension, hypokalemia, transaminasemia and proximal myopathy improved. Discussion:Ectopic ACTH mediated Cushing’s syndrome is responsible for about 5 - 20% of all Cushing’s syndrome cases. Pancreatic neuroendocrine tumor secreting Ectopic ACTH is rarer but can be aggressive. Clinical presentation can be confounding due to secretion of &amp;gt;1 neurohormone i.e ACTH and Gastrin in our patient. Gallium-DOTATATE PET/CT tracer has a very high sensitivity and specificity. Early use of this imaging may prevent comorbidity and mortality as surgical resection of ectopic ACTH secreting neuroendocrine tumor is first line therapy. Other diagnostic principles to consider are that severely elevated ACTH levels correlate only with a pituitary macroadenoma, IPSS is invasive and has relative contraindication in sick patients and Desmopressin stimulation test is not widely available. Presentation: 6/1/2024

6702 Management And Complications Of Metastatic Adrenocortical Carcinoma Presenting With Severe Cushing Syndrome

Abstract Disclosure: S. Rodrigues: None. A.K. Sumal: None. Background: Metastatic adrenocortical carcinoma (ACC) presenting with Cushing syndrome (CS) is a complicated, aggressive disease that commonly requires multiple adrenal steroidogenesis inhibitors and chemotherapy to achieve hormonal and tumor control. Clinical Case: A 66-year-old man with a history of prostate cancer and hypertension presented with right flank and back pain, worsening type 2 diabetes, profound proximal muscle weakness, and 3+ lower extremity edema to his thighs. CT and PET-CT revealed a 10.9 cm right adrenal mass with pericaval lymphadenopathy and metastatic disease at the L2 vertebral body. Laboratory testing demonstrated evidence of hypercortisolism with elevated 24-hour urinary cortisol excretion (449 mcg/24h; n&amp;lt;45 mcg/24h), and abnormal 1 mg dexamethasone suppression test (cortisol 15 mcg/dL; n&amp;lt; 1.8 mcg/dL) with suppressed ACTH (&amp;lt;6 pg/mL; n=7-63 pg/mL). Surgical resection of the primary tumor was aborted intraoperatively given the discovery of new peritoneal metastases, which were confirmed by biopsy to be metastatic ACC. He was started on mitotane and osilodrostat to manage his severe CS. He was also started on dexamethasone, both to prevent adrenal insufficiency and to avoid influencing serum cortisol measurements used to assess disease control. However, given his significant peripheral edema and weakness, he was functionally unable to receive chemotherapy. Despite rapid uptitration of mitotane and osilodrostat over three weeks, his CS remained uncontrolled, and he was ultimately hospitalized for lower extremity paralysis and septic shock due to pyelonephritis. Repeat imaging revealed severe spinal canal stenosis from an L2 pathologic fracture, as well as worsening hepatic, osseous, peritoneal, and retroperitoneal metastases. After recovery from his septic shock, he was started on chemotherapy with carboplatin and etoposide while hospitalized, but his mitotane was intermittently held due to elevated transaminases. His hospital course was complicated by hypotension requiring pressor support, atrial fibrillation, hemoperitoneum, worsening anasarca, and acute kidney injury requiring continuous renal replacement therapy. Given his worsening condition that precluded him from further chemotherapy or palliative radiation, he elected to pursue comfort care measures and expired shortly thereafter. Conclusion: This case highlights the therapeutic challenges of metastatic ACC presenting with life-threatening CS. Simultaneous use of multiple adrenal steroidogenesis inhibitors is often required for control of hypercortisolism, and chemotherapy is equally necessary to manage tumor burden. However, as in this case, disease-related complications can limit treatment management and result in rapid deterioration. Thus, early diagnosis and prompt treatment of metastatic ACC presenting with CS is critical to prevent morbidity and mortality. Presentation: 6/3/2024

7295 Giant Pituitary Adenoma with Rapid Symptomatic Progression and Postoperative Mortality

Abstract Disclosure: R.D. Kennedy: None. M. Nicholson: None. Introduction: Giant pituitary adenomas, defined as pituitary adenomas measuring greater than 4 cm, present a therapeutic challenge because of their size, clinical features, and increased potential for complications following surgical intervention. Early detection and intervention to prevent growth and progression is paramount. We present a case of a patient with a giant 6.3 cm pituitary adenoma who had significant neurologic compromise, requiring surgical intervention, with resultant postoperative complications and death. Case:Patient is a 41 year old male with known history of pituitary adenoma who presented on 11/1/2023, from outside hospital, to the Neuroendocrine clinic with complaints of excessive truncal obesity, impotence, fatigue, and apathy. Vital signs were within normal limits. Physical exam revealed clouding of consciousness, grossly intact cranial nerve function, truncal obesity, and diminished power, tone, and bulk of the extremities. Formal visual field testing revealed bitemporal hemianopsia. A head CT scan revealed a 6.3 cm sellar mass with expansion of the sella, invasion of soft tissue into the sphenoid sinus, and extension of soft tissue cranially to the level of the third ventricle eccentric to the left. There was no evidence of apoplexy. Lab results revealed Prolactin of 924 ng/mL. The patient had been taking Bromocriptine, 2.5 mg daily, for at least three weeks. Less than three weeks after his initial evaluation, he returned to the hospital with complaint of acute ataxia. Pituitary MRI revealed 6.3 cm sellar mass with evidence of acute and subacute blood products, stretching of the optic chiasm from mass effect, extension into the bilateral cavernous sinuses, superior left MCA displacement, posterior left PCA displacement, 5 mm midline shift, uncal herniation and descending transtentorial herniation. The patient underwent endoscopic transsphenoidal resection with subsequent craniotomy for debulking. Postoperatively, he developed new right sided hemiplegia with aphasia with subsequent MRI finding of watershed infarct at the left MCA/PCA lateral posterior border zone territories with increasing mass effect over a 30 day hospital stay. He developed progressive global edema with worsening uncal and tonsillar herniations. Brain death was pronounced on 11/30/23. Discussion:This case highlights the importance of early intervention in patients with giant pituitary adenomas. Our patient had been experiencing right sided weakness for at least one year prior to his admission to our facility. In this case, earlier treatment with a dopamine agonist may have decreased the size of the adenoma or prevented rapid growth. This may have precluded the need for surgical intervention on an adenoma of this size, which carries increased risk for postoperative complications. Presentation: 6/2/2024

Jejunal Dieulafoy's lesion - An exceptionally rare and challenging culprit of gastrointestinal bleeding.

A 78-year-old male presented to the emergency department with melena. He was hemodynamically stable but displayed a hemoglobin level of 5.8g/dL necessitating blood transfusion. Initial esophagogastroduodenoscopy and colonoscopy failed to identify a bleeding source, prompting a capsule endoscopy that revealed an active bleeding site in the jejunum. A single-balloon enteroscopy identified an aberrant vessel in the mid-jejunum protruding through a 3mm mucosal defect, devoid of surrounding inflammation, consistent with a Dieulafoy's lesion, in which two through-the-scope clips were applied. Despite this, ongoing melena and decreasing hemoglobin levels in the subsequent days led to a second single-balloon enteroscopy, which confirmed continued bleeding. Definitive hemostasis was achieved through diluted adrenaline injection, four additional through-the-scope clips, and polidocanol sclerotherapy. Jejunal Dieulafoy's lesion is extremely rare and presents notable diagnostic and therapeutic challenges. Ávila et al. recently reported a case where, despite capsule endoscopy identifying the bleeding site, single-balloon enteroscopy failed to confirm the diagnosis, leading to the use of motorized enteroscopy with argon and metallic clip treatment. Similarly, our experience highlights the diagnostic value of capsule endoscopy and the crucial role of device-assisted enteroscopy in a multimodal therapeutic approach, which was essential for achieving successful hemostasis.

Prospects for gene therapy in polycystic kidney disease.

We aim to provide an updated perspective on the recent advancements in gene therapy for polycystic kidney disease (PKD), a genetic disorder with significant morbidity. Given the rapid evolution of gene therapy technologies and their potential for treating inherited diseases, this review explores the therapeutic prospects and challenges in applying these technologies to PKD. Significant progress has been made in understanding the genetic underpinnings of PKD, making it a prime candidate for gene therapy. Re-expression of the PKD genes, treatment with the C-terminal tail of polycystin 1 protein and antagomir therapy against miR-17 have shown promise in reducing cyst formation and preserving kidney function. The rapid development of gene-editing tools, antisense oligonucleotide-based strategies, programmable RNA, and advanced gene delivery systems has opened new possibilities for PKD treatment. However, challenges such as off-target effects, delivery efficiency, and long-term safety remain significant barriers to clinical application. Current research highlights the transformative potential of gene therapy for PKD. Ongoing studies are crucial to overcoming existing challenges and translating these findings into clinical practice. We highlight the need for multidisciplinary efforts to optimize gene-editing technologies and ensure their safety and efficacy in treating PKD.

The Modulation of Septic Shock: A Proteomic Approach.

Sepsis poses a significant challenge due its lethality, involving multiple organ dysfunction and impaired immune responses. Among several factors affecting sepsis, monocytes play a crucial role; however, their phenotype, proteomic profile, and function in septic shock remain unclear. Our aim was to fully characterize the subpopulations and proteomic profiles of monocytes seen in septic shock cases and discuss their possible impact on the disease. Peripheral blood monocyte subpopulations were phenotype based on CD14/CD16 expression by flow cytometry, and proteins were extracted from the monocytes of individuals with septic shock and healthy controls to identify changes in the global protein expression in these cells. Analysis using 2D-nanoUPLC-UDMSE identified 67 differentially expressed proteins in shock patients compared to controls, in which 44 were upregulated and 23 downregulated. These proteins are involved in monocyte reprogramming, immune dysfunction, severe hypotension, hypo-responsiveness to vasoconstrictors, vasodilation, endothelial dysfunction, vascular injury, and blood clotting, elucidating the disease severity and therapeutic challenges of septic shock. This study identified critical biological targets in monocytes that could serve as potential biomarkers for the diagnosis, prognosis, and treatment of septic shock, providing new insights into the pathophysiology of the disease.

Treatment-Resistant Melasma Response to Oral Tranexamic Acid

Melasma, a common acquired hyperpigmentation disorder primarily affecting facial skin, poses significant therapeutic challenges due to the limited efficacy and potential side effects of available treatments. Tranexamic Acid (TXA), traditionally used for its hemostatic properties by inhibiting plasminogen activation, has emerged as a promising addition to protocols for treatment-resistant melasma. This study aims to evaluate the efficacy and safety of TXA in combination with Hydroquinone (HQ) and Kojic Acid (KA) in patients with treatment-resistant melasma. We present here a case series of fourteen patients with recurrent melasma refractory to common treatments who achieved successful outcomes with the addition of TXA to their treatment regimen. These patients received 650 mg of TXA in combination with 16% HQ and 6% KA. All patients exhibited a symmetrical reduction in their hyperpigmented patches following treatment and no significant adverse effects were reported. These cases contribute valuable input to the growing body of evidence on the use of TXA for melasma and the combination of treatments and dosing, suggesting its potential as a therapeutic option for this condition. Further research is warranted to explore the mechanisms by which TXA exerts its beneficial effects in melasma and to determine the optimal treatment protocols for achieving effective clinical outcomes.

Unveiling therapeutic avenues targeting xCT in head and neck cancer.

Head and neck cancer (HNC) remains a major global health burden, prompting the need for innovative therapeutic strategies. This review examines the role of the cystine/glutamate antiporter (xCT) in HNC, specifically focusing on how xCT contributes to cancer progression through mechanisms such as redox imbalance, ferroptosis, and treatment resistance. The central questions addressed include how xCT dysregulation affects tumor biology and the potential for targeting xCT to enhance treatment outcomes. We explore recent developments in xCT-targeted current and emerging therapies, including xCT inhibitors and novel treatment modalities, and their role in addressing therapeutic challenges. This review aims to provide a comprehensive analysis of xCT as a therapeutic target and to outline future directions for research and clinical application.

Covered Stent Graft for Treatment of Carotid Blowout Syndrome in Patients With Head and Neck Cancer

Carotid blowout syndrome (CBS) is a rare life-threatening complication of head and neck cancer that requires either surgical or endovascular treatment such as a carotid occlusion procedure or stent-graft placement. CBS outcomes and complications of its management using endovascular stent-graft placement remain unclear due to limited published data. Given that this treatment approach is increasingly used, understanding its efficacy and associated risks is paramount. To evaluate the periprocedural and postprocedural complications and outcomes associated with stent-graft treatment for CBS in patients with head and neck cancer. This case series study conducted at the Institut Gustave Roussy (Villejuif, France) between January 2006 and December 2021 included all eligible patients with head and neck cancer who experienced CBS and were referred for endovascular treatment. Risk factors and periprocedural and postprocedural data were collected retrospectively from medical records. Data analyses were performed from July 2022 to July 2024. Endovascular stent-graft placement for the treatment of CBS in patients with head and neck cancer. Periprocedural and postprocedural complications of stent-graft placement. Secondary outcomes were technical success, defined as immediate control of hemorrhage; 30-day and overall survival rates; and risk factors for mortality and rebleeding. Risk factors considered were body mass index (BMI), CBS presentation, hemodynamic status, tumor stage, and radiation dose. In all, 67 CBS-related stent-graft procedures were performed in 62 patients (mean [SD] age, 55.4 [10.1] years; 10 [16.1%] females and 52 [83.9%] males), most with advanced-stage head and neck cancer, over 15 years. The most frequently observed clinical complications were rebleeding (16 patients [38.8%]) and stroke (9 patients [13.4%]). Immediate hemostasis was achieved in 100% of cases. The survival rate was 77.3% (51 participants) at 30 days postprocedure, with a median (IQR) overall survival time of 59 (32-141.5) days. Acute CBS presentation (risk ratio, 4.30; 95% CI, 1.11-28.23) and BMI (risk ratio, 0.88; 95% CI, 0.77-0.99) showed a statistically significant association with 30-day mortality in univariate analysis. The findings of the case-series study indicate that CBS can be safely managed with endovascular stent-graft placement that preserves carotid patency; however, it carries significant risks of ischemia and rebleeding. These findings suggest that stent grafts should be used only in specific clinical scenarios. Despite achieving a high rate of technical success in controlling hemorrhage, the overall and 30-day survival outcomes underscore the critical implications of CBS in patients with cancer and its associated therapeutic challenges.

PDOC-01 THERAPEUTIC DIFFICULTY IN THE MANAGEMENT OF A RECURRENT CRANIOPHARYNGIOMA IN A CHILD: REVIEW OF THE LITERATURE AND CASE REPORT

Abstract BACKGROUND Craniopharyngiomas are rare, benign epithelial tumors of embryonic origin in children that develop along the craniopharyngeal duct from Rathke’s pouch. The optimal treatment algorithm remains challenging. We report a child case of recurrent craniopharyngioma with therapeutic challenges. CASE PRESENTATION 12-year-old patient, followed for a multi-operated type 2 craniopharyngioma (December 2017, November 2018, and April 2022), stroke on left sylvian stenosis with right hemiplegia in 2020 during proton therapy (52 Gray), thrombolysed with good recovery after rehabilitation, sequellar panhypopituitarism. He was seen in consultation for visual field deterioration. Clinical examination showed a conscious, coherent, obese patient with a deteriorating visual field. Ophthalmological examination showed visual acuity 10/10 with slight temporal visual field amputation on the left and monocular blindness on the right due to probable optic atrophy sequelae of the craniopharyngioma. Magnetic resonance imaging revealed progression of the residual multicystic lesion in the sellar and left temporal regions, entering the sylvian valley and severely compressing the optic pathways. The tumor was removed under general anesthetic in a supine position, with release of the optic nerve, the carotid artery, and its division, and the left 3rd cranial nerve. The postoperative course is straightforward. CONCLUSION Morbidity and the assessment of sequelae are now at the forefront of the management of craniopharyngiomas. The current therapeutic approach should be reconsidered, in terms of the indications for surgery and the surgical protocol. This patient’s case is a typical example of the therapeutic difficulties involved in the management of craniopharyngiomas.

Severe Fetal Akinesia At 19 Weeks: A Case Report

The term "fetal akinesia" is defined as a complete or partial absence of fetal movements. It can occur in isolation or be associated with other malformations, some of which can be lethal. The first observations of this syndrome were made by Péna and Shokeir in 1974 [1]. Since then, several cases have been reported, though the syndrome remains rare, with an estimated frequency between 1 in 3,000 and 1 in 15,000 births [2]. In some cases, the risk of recurrence can be as high as 25% [3]. In practice, the detection of fetal akinesia during an ultrasound examination is always a source of anxiety, accompanied by diagnostic, etiological, and therapeutic challenges.

"A Rare Encounter with Gastrointestinal Mucormycosis: Diagnostic and Therapeutic Challenges"

Mucormycosis is a very rare, life-threatening infection caused by fungi. Frequently observed in those patients having underlying immunosuppression, rarely found in immunocompetent patients. The infection can cause pulmonary, rhinocerebral, skin and soft tissue, central nervous system and gastrointestinal system. Nevertheless, gastrointestinal involvement is the rarest presentation. We present a rare case of invasive intestinal mucormycosis causing Gastrointestinal bleed in an adult female and review the literature, highlighting the rare clinical presentation, the need for high index of suspicion in the timely diagnosis and management of mucormycosis.

Multiple giant pancreatic pseudocysts, a rare complication of acute pancreatitis – A case report

A 34-year-old alcoholic male presented to our outpatient department with a complaint of persistent epigastric pain, radiating to the back with a swelling in the upper abdomen. He had 2 similar episodes in the past for which he was conservatively managed along the lines of acute pancreatitis. Now on physical examination, the patient had a massive lump in the upper abdomen reaching below the umbilicus. Examination findings were confirmed by computed tomography - abdomen (Plain and Contrast), two 13×10×09 cm and 9×8×7.8 cm, cystic lesions (Noncommunicating) were seen abutting the posterior wall of the stomach and into each other, suggestive of mature pseudocysts of the pancreas. The patient was admitted and after necessary investigations, surgical cystogastrostomy was done for the lower pseudocyst and cystocystostomy for the upper pseudocyst. The patient was discharged 5 days later with no complications. This case shows that multiple pseudocysts, a relatively rare complication of acute pancreatitis, are one of the differentials of acute abdomen. The treatment is a therapeutic challenge that depends on location, size, number as well as their relation to one another. Good drainage prevents resection procedures and further complications (exocrine and endocrine insufficiency).