Imatinib- and Nilotinib-Induced Lichenoid Eruption in Chronic Myeloid Leukemia: A Rare Case Report.

Imatinib and nilotinib are inhibitors of tyrosine kinases (TKIs) generated from the bcr-abl fusion protein, c-Kit, and platelet-derived growth factor receptors. Cutaneous adverse effects (AEs) of TKI are the most frequent non-hematological sequelae. In our case, the common molecular target raises the possibility that cross-intolerance, in which similar AEs occur with both agents, can arise. We hereby report a rare case report on cross-intolerance of cutaneous AEs of imatinib and nilotinib in chronic myeloid leukemia.

Intrastromal Corneal Ring Segment Implantation Followed by Simultaneous Topography-Guided Photorefractive Keratectomy and Corneal Cross-Linking for Contact Lens-Intolerant Keratoconus.

PURPOSE: This study aimed to evaluate the efficacy and safety of Keraring implantation followed by simultaneous topography-guided photorefractive keratectomy (TGPRK) and corneal cross-linking (CXL) in the management of keratoconus. METHODS: This is a single-center, private practice, retrospective review. Patients with keratoconus who were intolerant to contact lens wear underwent implantation of the Keraring, followed by TGPRK with CXL from 2 to 36 months after implantation. Main outcome measures were uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), refraction (cylinder and spherical equivalent), keratometry (steep, maximum, and central), and central corneal thickness (CCT). Patients were followed up for 3 to 60 months postoperatively. RESULTS: Fifty-seven eyes from 45 patients were included. The mean time between Keraring and TGPRK/CXL was 6.0 ± 6.0 months. Patients were followed up for a mean of 28.6 ± 20.1 months after Keraring insertion. At 12-month follow-up, there was a statistically significant improvement in mean UDVA (0.94 ± 0.49-0.35 ± 0.23, P < 0.01), CDVA (0.39 ± 0.26-0.17 ± 0.15, P < 0.01), cylinder (-4.97 ± 2.68 to -1.74 ± 1.25, P < 0.01), steep keratometry (51.25 ± 3.37-45.03 ± 2.27, P < 0.01), central keratometry (52.59 ± 4.98-46.99 ± 3.53, P < 0.01), and maximum keratometry (58.78 ± 4.22-50.76 ± 3.42, P < 0.01). These results were sustained at 48-month follow-up. CCT decreased at 12 months after TGPRK (461.84 ± 27.46-418.94 ± 45.62, P < 0.01) and remained stable at 60 months. Postoperatively, 2 eyes (3.51%) had corneal haze, resulting in decrease in CDVA; 1 was treated successfully with repeat PRK; and 1 patient (1.75%) had wound melt due to partial Keraring extrusion, which settled with repositioning. CONCLUSIONS: Keraring implantation followed by simultaneous TGPRK and CXL appears to be effective in the long term in improving UDVA, CDVA, cylinder, CCT, and keratometry in patients with keratoconus who are intolerant to contact lenses.

Comparison of standard versus accelerated corneal collagen cross-linking for keratoconus: 5-year outcomes from the Save Sight Keratoconus Registry.

OBJECTIVE: To compare long-term effectiveness of Standard (UV intensity: 3 mW/cm2, duration: 30 min) vs Accelerated (UV intensity: 9 mW/cm2, duration: 10 min) corneal cross-linking (CXL) for stabilising keratoconus. METHODS: Data for this observational study were captured through a web-based registry system from the routine clinical practice (15 sites across Australia, New Zealand and Italy). The outcomes were compared using mixed-effects regression models. A total of 100 eyes (75 patients) who had standard CXL and 76 eyes (66 patients) who had accelerated CXL, with a follow-up visit at five-year post-CXL were included. RESULTS: Both CXL protocols were effective and safe in stabilising keratoconus and improving outcomes. The adjusted mean changes (95% CI) in outcomes were better in standard CXL than in accelerated CXL [visual acuity gain, 10.2 (7.9-12.5) vs 4.9 (1.6-8.2) logMAR letters; pinhole visual acuity 5.7 (3.5-7.8) vs 0.2 (-2.2 to 2.5) logMAR letters; Kmax -1.8 (-4.3 to 0.6) vs 1.2 (-1.5 to 3.9)D; K2 -0.9 (-2.2 to 0.3) vs 0.1 (-1.3 to 1.6)D; MCT -3.0 (-13.7 to 7.7) vs -11.8 (-23.9 to 0.4) µm (p values for visual acuity, pinhole visual acuity, Kmax: <0.05; for K2 and MCT: >0.05)]. The frequency of adverse events at the 5-year follow-up visit was low in both groups [standard, 5 (5%; haze 3; scarring 1, epithelial defect 1) and accelerated 3 (3.9%; haze 2, scarring 1)]. CONCLUSIONS: Both standard and accelerated CXL were safe and effective procedures for stabilising keratoconus in the long term. The standard CXL resulted in greater improvements in visual acuity and keratometry.

The heparin-binding hemagglutinin protein of Mycobacterium tuberculosis is a nucleoid-associated protein.

Nucleoid-associated proteins (NAPs) regulate multiple cellular processes such as gene expression, virulence, and dormancy throughout bacterial species. NAPs help in the survival and adaptation of Mycobacterium tuberculosis (Mtb) within the host. Fourteen NAPs have been identified in Escherichia coli; however, only seven NAPs are documented in Mtb. Given its complex lifestyle, it is reasonable to assume that Mtb would encode for more NAPs. Using bioinformatics tools and biochemical experiments, we have identified the heparin-binding hemagglutinin (HbhA) protein of Mtb as a novel sequence-independent DNA-binding protein which has previously been characterized as an adhesion molecule required for extrapulmonary dissemination. Deleting the carboxy-terminal domain of HbhA resulted in a complete loss of its DNA-binding activity. Atomic force microscopy showed HbhA-mediated architectural modulations in the DNA, which may play a regulatory role in transcription and genome organization. Our results showed that HbhA colocalizes with the nucleoid region of Mtb. Transcriptomics analyses of a hbhA KO strain revealed that it regulates the expression of ∼36% of total and ∼29% of essential genes. Deletion of hbhA resulted in the upregulation of ∼73% of all differentially expressed genes, belonging to multiple pathways suggesting it to be a global repressor. The results show that HbhA is a nonessential NAP regulating gene expression globally and acting as a plausible transcriptional repressor.

Neuroimaging Spectrum in COVID-19 Infection: A Single-Center Experience.

Background and Purpose The ongoing coronavirus disease 2019 (COVID-19) pandemic is a multisystemic disease and involvement of the nervous system is well established. The neurological and neuroimaging features of the disease have been extensively evaluated. Our study aimed to elucidate the neuroradiological findings in COVID-19 infected patients admitted to our institute during the first and second waves of the pandemic in India. Methods This was a single-center retrospective study of all COVID-19 positive patients who underwent neuroimaging between March 2020 and May 2021. The presenting neurological complaints, the imaging findings in computed tomography (CT) imaging, and/or magnetic resonance imaging (MRI) were recorded. They recorded the findings in the subheadings of ischemic stroke, hemorrhagic stroke, parainfectious demyelination, acute encephalitis syndrome, and changes of global hypoxic changes. Patients with age-related, chronic, and incidental findings were excluded. Results The study comprised of 180 COVID-19 positive patients who underwent neuroimaging. CT scan was performed for 169 patients, MRI for 28, and a combination of both CT and MRI was performed for 17 patients. Seventy percent of patients were males, and median age was 61.5 years (interquartile range: 48.25-70.75). Out of the 180 patients, 66 patients had nonspecific findings that could not be attributed to COVID-19 infection. In the remaining 114 patients, 77 (42.7%) had ischemic findings, while 22 (12.2%) had hemorrhagic stroke. Hypoxic ischemic changes were noted in five patients. The rest of the patients had a spectrum of changes including, cerebellitis (3), tumefactive demyelination (1), COVID-19-associated encephalitis (1), hemorrhagic acute demyelinating encephalomyelitis (1), transverse myelitis (1), cytotoxic lesions of corpus callosum (1), Guillain-Barre syndrome (1), and COVID-19-associated microhemorrhages (1). Conclusion Neurological manifestations of COVID-19 infection are not uncommon, and our understanding of this topic is expanding. A complex interplay of neurotropism and direct central nervous system invasion, immune activation and cytokine storm, vasculitis, and parainfectious processes are implicated in the pathophysiology. While the most common imaging finding was ischemic stroke, followed by hemorrhagic stroke, a diverse range of parainfectious findings was also noted in our study.

Addisonian pigmentation associated with acute lymphoblastic leukemia: A rare paraneoplastic phenomenon.

Addisonian pigmentation usually presents with nonspecific symptoms and signs, which are often ignored or misdiagnosed as a sign of other more common diseases. We present a case of 12-year-old child in whom diffuse Addisonian hyperpigmentation of skin was associated with underlying acute lymphoblastic leukemia (B-type), a rare paraneoplastic phenomenon in hematological malignancies.

Heart Transplantation from COVID-19-Positive Donors: A Word of Caution.

BACKGROUND: During the COVID-19 pandemic, efforts to maintain solid-organ transplantation have continued, including the use of SARS-CoV-2-positive heart donors. METHODS: We present our institution's initial experience with SARS-CoV-2-positive heart donors. All donors met our institution's Transplant Center criteria, including a negative bronchoalveolar lavage polymerase chain reaction result. All but 1 patient received postexposure prophylaxis with anti-spike monoclonal antibody therapy, remdesivir, or both. RESULTS: A total of 6 patients received a heart transplant from a SARS-CoV-2-positive donor. One heart transplant was complicated by catastrophic secondary graft dysfunction requiring venoarterial extracorporeal membrane oxygenation and retransplant. The remaining 5 patients did well postoperatively and were discharged from the hospital. None of the patients had evidence of COVID-19 infection after surgery. CONCLUSION: Heart transplants from SARS-CoV-2 polymerase chain reaction-positive donors are feasible and safe with adequate screening and postexposure prophylaxis.

Normocalcemic Parathyroid Adenoma with Brown's Tumor Maxilla: A Rare Case.

Introduction: Primary hyperparathyroidism due to parathyroid adenoma commonly causes raised serum calcium and focal giant cell lytic lesions in bones known as Brown's tumors. It is more common in females in the post-menopausal age group. Case Report: We report a case of a 29-year-old female patient with Brown's tumor maxilla in a clinical setting of normocalcemic primary hyperparathyroidism. The patient presented to us with facial and palatal swelling for which FNAC was done. Cytology revealed hemosiderin-laden macrophages suspicious for Brown's tumor. On further imaging studies such as CT Neck, Tc99 Sestamibi scan, and other biochemical tests like parathyroid hormone assay and serum calcium level, the diagnosis of a hyperfunctioning parathyroid gland with normal calcium level was made. Parathyroidectomy was performed and parathyroid adenoma came out to be the primary pathology. On post-operative follow up there was regression of the swelling on the face and palate relieving the patient symptomatically. Conclusion: The diagnostic suspicion of primary hyperparathyroidism should be kept in mind whenever a young female presents with suspected Brown's tumor, even with normal serum calcium levels, for appropriate management. Ours was a highly uncommon case that was a diagnostic challenge and had a successful treatment outcome. Very few such cases have been reported in the literature to date to the best of our knowledge.

Polymicrobial Infections in the Immunocompromised Host: The COVID-19 Realm and Beyond.

Immunosuppression changes both susceptibility to and presentation of infection. Infection with one pathogen can also alter host response to a different, unrelated pathogen. These interactions have been seen across multiple infection domains where bacteria, viruses or fungi act synergistically with a deleterious impact on the host. This phenomenon has been well described with bacterial and fungal infections complicating influenza and is of particular interest in the context of the COVID-19 pandemic. Modulation of the immune system is a crucial part of successful solid organ and hematopoietic stem cell transplantation. Herein, we present three cases of polymicrobial infection in transplant recipients. These case examples highlight complex host-pathogen interactions and the resultant clinical syndromes.

Multiphase computed tomography angiography (mCTA) derived source images in acute ischemic stroke: Beyond collaterals. Can it obviate the need for computed tomography perfusion (CTP)?

BACKGROUND AND PURPOSE: To compare Multiphase CT Angiography derived source images (mCTA-SI) in acute ischemic stroke (AIS) with CT Perfusion (CTP) derived automated color maps of cerebral blood flow (CBF) and cerebral blood volume (CBV) and to assess the comparability of mCTA-SI with CTP in the prediction of final radiological and clinical outcome. METHODS: This prospective single-centre observational study comprised of patients with AIS of the anterior circulation, presenting within 24 h and undergoing neuroimaging under stroke protocol with follow-up. Non-contrast computed tomography (NCCT), mCTA, and CTP were acquired with follow-up NCCT at 24 h and modified Rankin score (mRS) at 3 months. mCTA-SI and CTP color maps were scored by the ASPECTS (Alberta Stroke program early CT score) method and compared amongst each other and with the outcome. ROC (Receiver operating characteristic) curves were plotted considering mRS 0-2 and FIV≤ 28 ml as favourable clinical and radiological outcomes respectively. RESULTS: The study included 55 patients. The 1st and 2nd phase of mCTA-SI correlated significantly with CBF maps (r = 0.845, p < 0.01, r = 0.842, p < 0.01 respectively). 3rd phase of mCTA-SI correlated significantly with CBV maps (r = 0.904, p < 0.01). A favourable functional and radiological outcome was best predicted by the 1st (AUC 0.8, 95%CI 0.671-0.896) and 2nd ( AUC 0.895, 95% CI 0.783-0.962) phase of mCTA-SI respectively. CONCLUSIONS: The 1st and 2nd phases of mCTA-SI produces results congruent to CBF color maps and the 3rd phase of mCTA-SI simulate CBV color maps. In addition to predicting radiological and functional outcomes, mCTA can predict the salvageable and non-salvageable tissue in AIS and is non-inferior to CTP.

Diagnostic yield of candidate genes in an Australian corneal dystrophy cohort.

Corneal dystrophies describe a clinically and genetically heterogeneous group of inherited disorders. The International Classification of Corneal Dystrophies (IC3D) lists 22 types of corneal dystrophy, 17 of which have been demonstrated to result from pathogenic variants in 19 identified genes. In this study, we investigated the diagnostic yield of genetic testing in a well-characterised cohort of 58 individuals from 44 families with different types of corneal dystrophy. Individuals diagnosed solely with Fuchs endothelial corneal dystrophy were excluded. Clinical details were obtained from the treating ophthalmologist. Participants and their family members were tested using a gene candidate and exome sequencing approach. We identified a likely molecular diagnosis in 70.5% families (31/44). The detection rate was significantly higher among probands with a family history of corneal dystrophy (15/16, 93.8%) than those without (16/28, 57.1%, p = .015), and among those who had undergone corneal graft surgery (9/9, 100.0%) compared to those who had not (22/35, 62.9%, p = .041). We identified eight novel variants in five genes and identified five families with syndromes associated with corneal dystrophies. Our findings highlight the genetic heterogeneity of corneal dystrophies and the clinical utility of genetic testing in reaching an accurate clinical diagnosis.

Omicron sub-variants: is the world going to witness another wave?

Omicron, the new 'Variant of Concern' of SARS-CoV-2, is rapidly evolving into new sub-variants or sub-lineages (BA.1, BA.2 etc.). These sub-variants have higher transmissibility, decreased vaccine effectiveness and increased risk of reinfection. As a result, many nations across the globe are reporting surge in infections which is a matter of concern. Understanding Omicron and its sub-variants is vital for development of public health policy and preventing disease transmission. The present paper throws a spotlight on the newly detected sub-variants of Omicron as reported in ongoing researches which are available only in pre-print form and also the importance of a booster dose of the vaccine. Information regarding recent research on a new nasal vaccine formulation, which may be effective against the new variants, is also highlighted in the paper.

In Vitro and In Vivo Activity of Amoxicillin-Clavulanate Combined with Ceftibuten or Cefpodoxime Against Extended-Spectrum ß-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae.

Infections due to extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales are an increasingly common problem. For many of these infections, no oral treatment options are available. The activity of amoxicillin-clavulanate combined with ceftibuten or cefpodoxime was evaluated against a group of Escherichia coli and Klebsiella pneumoniae clinical isolates possessing a variety of CTX-M- and SHV-type ESBLs; some possessed blaTEM1 as well. In time-kill studies, the combination of subinhibitory concentrations of amoxicillin-clavulanate with ceftibuten was bactericidal and synergistic for all strains with an amoxicillin-clavulanate MIC ≤32 µg/mL, regardless of the type of ESBL and the cephalosporin minimal inhibitory concentration (MIC). The combination with cefpodoxime was also bactericidal and synergistic against all but one of these strains. These combinations were further tested against two strains of K. pneumoniae and one E. coli in a sepsis model using Galleria mellonella larvae. The combination of amoxicillin-clavulanate with ceftibuten demonstrated a synergistic survival benefit against all three strains. The combination with cefpodoxime also improved survival against the two K. pneumoniae strains, but not the E. coli strain. These findings support combining amoxicillin-clavulanate with ceftibuten, and possibly cefpodoxime, for the treatment of infections due to ESBL producers and suggest that having an amoxicillin-clavulanate MIC of 32 µg/mL or less may predict activity at clinically achievable concentrations. Clinical studies are warranted to further evaluate this therapeutic approach.

Relationship of TonB-dependent receptors with susceptibility to cefiderocol in clinical isolates of Pseudomonas aeruginosa.

OBJECTIVES: Cefiderocol maintains activity against most MDR Gram-negative pathogens including Pseudomonas aeruginosa. In laboratory-derived isolates, down-regulation of TonB-dependent siderophore receptors have been implicated in resistance to cefiderocol. METHODS: In this report, the expression of seven TonB-dependent siderophore receptors was examined in 10 clinical isolates with cefiderocol MICs ranging from ≤0.03-8 mg/L. In addition, genetic sequences of the siderophore receptors were analysed to identify potentially disruptive mutations. RESULTS: There was no clear association between expression of the receptors with cefiderocol susceptibility, including the receptors piuA/piuD and pirA previously implicated in cefiderocol uptake. In addition, there were no disabling mutations identified in the receptors. Acquired ß-lactamase activity also could not explain the range in cefiderocol susceptibility. CONCLUSIONS: The aetiology of reduced susceptibility to cefiderocol in clinical isolates of P. aeruginosa remains an enigma and worthy of further investigation.

A Combination of Synthetic Molecules Acts as Antifreeze for the Protection of Skin against Cold-Induced Injuries.

Seasonal and occupational exposure of the human body to extreme cold temperatures can result in cell death in the exposed area due to the formation of ice crystals. This leads to superficial or deep burn injury and compromised functionality. Currently available therapeutics can be ineffective in extreme cases, and thus, it is necessary to develop prophylactic strategies. In this study, we have devised a combination of known synthetic cryopreservative agents (termed SynAFP) and evaluated their potential antifreeze applications on skin. The prophylactic activity of SynAFP in vitro is indicated by improved cellular revival and cell viability, retention of the cytoskeleton, and normal cell cycle progression even after cold stress. A comprehensive whole-cell proteomic approach revealed that in the presence of SynAFP, cold-induced downregulation of proteins involved in cell-cell adhesion and upregulation of those related to mitochondrial stress were ameliorated. Pre-application of SynAFP in mice facing a frostbite challenge prevents their skin from incurring significant injury as confirmed through macroscopic and histological examination. Moreover, multiple applications of SynAFP on mouse skin at room temperature did not compromise skin integrity. SynAFP was also formulated in anAloe vera-based cream (referred to as fSynAFP), which offered similar protection under cold stress conditions. Thus, SynAFP can be considered as a potential candidate for formulating a topical intervention for protection from cold-induced injuries to skin.

Magnetic Resonance Imaging in Coronavirus Disease - 2019 Associated Rhino-Orbital-Cerebral Mucormycosis (CA-ROCM) - Imaging Analysis of 50 Consecutive Patients.

BACKGROUND AND PURPOSE: Rhino-orbital-cerebral mucormycosis has emerged as a major opportunistic infection in patients with COVID-19. High clinical suspicion and prompt imaging are crucial for early diagnosis and management. Our study evaluates imaging characteristics of patients with COVID-19 associated Rhino-orbital-cerebral Mucormycosis (CA-ROCM) in a tertiary care hospital in India. MATERIALS AND METHODS: A retrospective analysis of clinical and imaging data of patients with CA-ROCM who presented between December 2020 to June 2021 was performed. All patients had microbiologically or histologically proven sino-nasal mucormycosis along with documented SARS-CoV-2 positive RT-PCR test and/or classical lung imaging features of COVID-19 infection. The extent of sinus involvement, bony erosions, extra-sinus soft tissue extension, orbital-intracranial invasion, perineural spread, and vascular complications were assessed. RESULTS: Fifty patients were included for the final analysis. Diabetes was the most common associated comorbidity. Seven patients presented with stage I disease, 18 patients with stage II, and 25 patients with stage III disease. The stage of disease showed a positive statistical correlation with HbA1c levels using Pearson's correlation. The common imaging features were "Black turbinate sign" and nonenhancing sino-nasal mucosa (82%), orbital involvement (76%), and diffusion restriction in the optic nerve (24%). Intracranial involvement was seen as perineural extension into the brain (42%), cerebritis (30%), and internal carotid artery involvement (16%). CONCLUSIONS: CA-ROCM is an acute invasive fungal sinusitis with an aggressive clinical course. Black-turbinate sign and peri-antral soft tissue infiltration are early features, whereas extra-nasal tissue infarction, optic nerve diffusion restriction, and vascular invasion are seen with advanced disease.

High prevalence of hepatic steatosis and hepatic fibrosis in patients with type 2 diabetes mellitus.

AIM: To determine the prevalence of hepatic steatosis and fibrosis in patients with T2DM from North India. RESEARCH DESIGN AND METHODS: In this cross-sectional study, Asian Indian patients with T2DM (n,250) underwent liver ultrasonography (USG), Fibroscan for assessment of hepatic steatosis (Controlled Attenuation Parameter, CAP) and hepatic fibrosis (Kilopascals, kPa) respectively. Pearson's correlation analysis & logistic regression analysis for significant predictors of hepatic steatosis and fibrosis were done. The cut-off value of liver span was calculated by ROC-AUC analysis. RESULTS: Grade 3 hepatic steatosis was seen in 213 T2DM patients (85.2%). It was higher in males than females and in those with high BMI values. Any degree of fibrosis and severe fibrosis were seen in 205 (62%) and 46 (18.4%) patients, respectively; these were higher in males, specifically in those with BMI >30 kg/m2, and diabetes of a duration more than 5 years. BMI and SGPT were the significant predictors of hepatic steatosis. An increase of 1 unit of BMI above 23 kg/m2 led to 19.6 times increased risk of hepatic steatosis in T2DM patients aged 50 years and above. SGOT and GGTP were significant predictors of any degree of hepatic fibrosis. On ROC-AUC analysis, liver span cut-off values of ≥16.4 cms and ≥16.8 cm in males and females respectively, were predictive of hepatic fibrosis. CONCLUSION: High prevalence of grade 3 hepatic steatosis and hepatic fibrosis needs increased vigilance and corrective lifestyle and pharmacological measures. Asian Indian patients with T2DM and BMI >30 kg/m2, with duration of diabetes above 5 years & an ultrasound derived liver span ≥16.4 cms, should be further evaluated for hepatic fibrosis.

Goserelin Ovarian Ablation Failure in Premenopausal Women With Breast Cancer.

Breast cancer is the most prevalent cancer known worldwide in women. It is a heterogeneous, phenotypically diverse disease composed of several biologic subtypes that have distinct behavior and response to therapy. Hormone receptor-positive (i.e., estrogen [ER] and/or progesterone [PR] receptor-positive) breast cancers comprise the most common types of breast cancer, accounting for 75% of all cases. This makes endocrine therapy the standardized treatment for patients with ER+/PR+ breast cancer. Drugs that block estrogen receptors or that lower estrogen levels are the mainstay of treatment. High-risk patients benefit from the addition of ovarian function suppression (OFS)/ablation to either an aromatase inhibitor (AI) or tamoxifen. This case report discusses a 36-year-old premenopausal female who presented with an abnormal right breast lump in the upper outer quadrant of the right breast. Due to high suspicion of malignancy, a biopsy was performed which showed features of both lobular and ductal carcinoma with ER and PR positivity, HER 2 was negative. The patient underwent mastectomy with axillary lymph node removal due to concern for multifocal disease. No clinically relevant genetic mutations were present. Oncotype DX breast recurrence score was 16 and no chemotherapy was offered. Due to large tumor size, young age OFS with goserelin 3.6mg/28 days and letrozole 2.5 mg once daily was recommended. After 16 months of treatment, the patient developed a failure of goserelin-induced ovarian suppression. This case report highlights the possibility of the development of hormonal resistance after long-term use of goserelin.