Case report: A severe case of zoledronate-associated diffuse orbital inflammation and uveitis in a patient with metastatic breast cancer.

Introduction: Zoledronate is a commonly prescribed medication to maintain bone health; however, a rare side effect includes ocular inflammation. We report a case of simultaneous anterior uveitis and orbital inflammation associated with zoledronate infusion in a patient with metastatic breast cancer. We also performed a literature search to provide an up-to-date summary of cases with zoledronate-associated ocular inflammation. Methods: This is a case report with literature review. Literature search (timeline 2010 to 2023) was performed using PubMed with the search team: (zoledronate) AND (uveitis OR scleritis OR orbital inflammation OR ocular inflammation). Results: A 48-year-old female presented with left eye pain, swelling, and decreased vision 2 days after receiving zoledronic acid infusion. An ophthalmic exam showed non-granulomatous anterior uveitis. CT orbits and ocular ultrasound showed signs of posterior scleritis and orbital inflammation. Ocular inflammation caused by an infection or metastatic cancer was ruled out. The patient was treated with both topical and systemic corticosteroids. Complete resolution of the inflammation occurred after 2.5 weeks. Conclusion: Orbital inflammation and uveitis are an uncommon side effect of zoledronate but needs to be promptly recognized and treated to prevent sight-threatening complications.

The efficacy of bisphosphonates for osteoporosis in young Cushing's disease patients with biochemical remission: a retrospective cohort study.

Background: Patients with Cushing's disease (CD) often experience slow recovery of bone mineral density (BMD), and the effectiveness of anti-osteoporosis drugs in young CD patients who have achieved biochemical remission after surgery is not well understood. Therefore, we aimed to explore whether bisphosphonates could help accelerate the recovery of osteoporosis in young CD patients with remission. Methods: We retrospectively enrolled 34 young patients with CD who achieved postoperative biochemical remission. All patients suffered from osteoporosis before surgery and were divided into postoperative bisphosphonate treatment group (16 cases) and without bisphosphonate treatment group (18 cases). Clinical data, BMD (Z Value), and bone turnover markers were collected at the time of diagnosis and one year after successful tumor resection. Results: The Z values in the lumbar spine showed slight improvement in both groups at follow-up compared to baseline, but this improvement was not statistically significant. There was no significant difference observed between the two groups at follow-up. One year after operation, bone formation markers (OC and P1NP) were significantly higher than those at baseline in both groups. However, OC and P1NP in the bisphosphonate treatment group were lower than those in control group at one year follow-up. In without bisphosphonate treatment group, ß-CTX from follow-up visit was higher than that at baseline, while no significant difference was observed in the bisphosphonate treatment group before and after surgery. Conclusion: Young patients with Cushing's disease combined with osteoporosis might not benefit from bisphosphonate therapy for osteoporosis recovery in the first year after achieving biochemical remission.

Prevalence and risk factors for atypical femoral fracture among Lebanese patients with hip and shaft fractures.

This retrospective study investigates the prevalence of atypical femoral fractures (AFFs) among patients admitted with hip and shaft fractures at a tertiary referral center in Beirut, Lebanon. We analyzed electronic medical records and radiology studies of patients aged above 40 admitted with hip and shaft fractures between January 2006 and December 2019. Fractures were confirmed by ICD9 or ICD10 codes. All cases were reviewed by radiologists, and AFFs were identified according to the 2013 revised ASBMR criteria. We identified 1366 hip and shaft fracture patients, of which 14 female patients had 19 AFFs. This represents a prevalence of 1.0% among all hip and shaft fractures patients and 1.7% among all female hip and shaft fracture patients. Bilateral AFFs were found in 5 of the 14 patients. Patients with AFF tended to be younger, with a mean age of 74.3 (±8.6) yr compared to 78.0 (±10.6) for patients with non-AFF fractures. A total of 36% of AFF patients had a prior history of non-traumatic fracture at first admission. A high percentage of patients with AFFs reported intake of proton pump inhibitors (42.9%) and glucocorticoids (21.4%). Bisphosphonate exposure was noted in 64.3% of AFF patients. None of the AFF patients were active smokers or consumed alcohol regularly. BMD assessments were available for 7 AFF patients, indicating osteoporosis in 4 and osteopenia in 3 cases. Hip axis length measurements showed no significant difference between AFF patients (N = 7) and sex and age-matched controls (N = 21). The study underlines the prevalence and characteristics of AFFs in Lebanon, which is consistent with the numbers reported in the literature (0.32%-5%). A larger prospective study that includes hospitals across the nation is needed to gain a more comprehensive view of the prevalence of AFFs in the Lebanese population.

Preparation and characterization of bis-phosphonated polycarbohydrates.

A simple, cost-effective, one-pot method was proposed to introduce bis-phosphonic groups onto alginic acid and carboxymethyl cellulose (CMC). New derivatives were characterized by means of nuclear magnetic resonance, X-ray photoelectron, and attenuated total reflectance Fourier transform infrared spectroscopy. These analyses confirmed the successful transformation of carboxylic groups present in alginic acid and CMC into bis-phosphonic groups. Additionally, thermogravimetric analysis coupled with differential scanning calorimetry was employed to investigate the thermal properties of the bis-phosphonic derivatives of alginate and CMC. The results clearly demonstrate the char-forming ability of both studied bis-phosphonated polycarbohydrates, suggesting their potential as intumescent materials.

Doping control analysis of myo-inositol trispyrophosphate and 10 bisphosphonates in equine plasma by ion chromatography-mass spectrometry and its application to clodronic acid horse administration.

Bisphosphonates and myo-inositol trispyrophosphate (ITPP) are two classes of difficult-to-detect polar drugs that are prohibited under the rules of racing. ITPP is a drug capable of increasing the amount of oxygen in hypoxic tissues, and studies have shown that administration of ITPP increases the maximal exercise capacity in mice. The properties of ITPP make it an ideal candidate as a doping agent to enhance performance in racehorses. In recent years, ITPP had indeed been detected in racehorses and confiscated items. As for bisphosphonates, it is especially critical to control their use as since February 2019, the International Agreement on Breeding, Racing and Wagering (IABRW) by the International Federation of Horseracing Authorities (IFHA) had identified specific conditions on which bisphosphonates should not be administered to a racehorse. A recent review of literature shows that there is yet a simultaneous screening method for detecting ITPP and bisphosphonates in equine samples. This paper describes an efficient ion chromatography high-resolution mass spectrometry (IC-HRMS) method for the simultaneous detection of ITPP and 10 bisphosphonates at sub-parts-per-billion (ppb) to low-ppb levels in equine plasma after solid-phase extraction (SPE) and its application to an administration study of clodronic acid in horses.

Impending Atypical Femoral Fracture on the Contralateral Side Progressed to a Complete Fracture Early after Surgery for an Atypical Femoral Fracture: A Case Report.

Introduction: Long-term bisphosphonate (BP) administration may cause an atypical femoral fracture that is occasionally bilateral. We encountered a case of an impending atypical femoral fracture on the contralateral side that progressed to a complete fracture early after surgery for an atypical femoral fracture. Case Report: An 83-year-old woman who had received long-term BP therapy developed a right femoral atypical incomplete fracture that progressed to a complete fracture 5 days after surgery for an atypical complete left femoral fracture. Conclusion: The findings from this case suggest that when an atypical femoral fracture occurs in patients receiving long-term BP therapy, the possibility of an impending atypical femoral fracture on the contralateral side should be considered, and radiographs or CT images should be obtained for both legs. To prevent long-term bed rest in older adults, one- or two-stage bilateral surgery should be considered when imaging reveals bilateral atypical femoral fractures.

Does Early Treatment With Teriparatide Prevent the Need for Surgical Intervention in Osteoporotic Vertebral Compression Fractures.

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVE: The primary objective of this study is to evaluate the efficacy of early administration of Teriparatide in preventing the necessity of surgical intervention in individuals with osteoporotic vertebral compression fractures. METHODS: In a 24-month follow-up retrospective analysis, 191 OVCF patients from January 2016 to October 2020 were randomly assigned to Non teriparatide Group A (n = 104) or Group B teriparatide (n = 87). At baseline, 6 months, 1 year, and 2 years following treatment, demographic data and need of surgical intervention, VAS, ODI, union rates, and kyphosis development, were examined. RESULTS: Our study found that non-teriparatide group individuals had an 11.53% higher risk of non-union formation that required surgery. Only 8.63% of teriparatide group patients needed surgery. Both groups had significant VAS score reductions. Non-teriparatide group scores declined from 8.38 ± 0.74 to 3.15 ± 1.40, while teriparatide group scores decreased from 8.49 ± 0.73 to 1.11 ± 0.31. The 2-year follow-up ODI scores significantly decreased, with values of 25.02 ± 13.94 for non-teriparatide patients and 15.11 ± 2.17 for teriparatide patients. The kyphosis progression angles in the teriparatide group were considerably lower (4.97 ± 0.78°) compared to the other group (8.09 ± 1.25°). CONCLUSION: With increasing elderly populations, it is necessary to take measures to prevent surgical intervention in osteoporotic spinal compression fractures. Teriparatide can be employed as an early medication in the management of these fractures to avert non-union and the minimise the progression of kyphosis.

Risedronate-Induced Chronic Drug Fever in a Case of Parkinson's Disease.

We present an atypical case of risedronate-induced chronic fever in an 85-year-old woman with Parkinson's disease, with a dosage regimen of 17.5 mg/week. Our patient had been administered an analgesic/antipyretic drug, acetaminophen, at a rate of 600 mg/day for treatment of a vertebral fracture that occurred relatively frequently, which might have masked the fever caused by risedronate. We noted two clinically significant indications. Firstly, blood test results do not necessarily show the cause of risedronate-induced fever, as white blood cell counts and C-reactive protein levels vary. A simple way to diagnose risedronate-induced fever is to suspend risedronate for a certain period and observe if the patient's fever lowers. Secondly, in general, cases receiving polypharmacy tend to include an analgesic antipyretic agent, which may mask the drug-induced fever. Even in patients with Parkinson's disease whose body temperature is generally unstable due to autonomic nerve system disorder, if they are administered risedronate and experience chronic fever of unknown cause, the possibility of drug fever may be considered. This study concludes that risedronate-induced chronic fever, as observed in our case, represents a rare phenomenon, and it may be necessary to reconsider treatment methods for osteoporosis.

Posterior scleritis following a single infusion of zoledronate for osteoporosis: A case report and literature review.

The most frequently reported adverse reaction to zoledronic acid is an acute phase reaction resembling influenza. While rarer adverse events such as osteonecrosis of the jaw and atypical femoral fractures have gained significant recognition, the ocular adverse effects, particularly scleritis, are not yet fully comprehended. Here, we present the case of a 75-year-old female patient with osteoporosis who developed bilateral redness and intense eye pain 48 h after receiving a 5 mg intravenous dose of zoledronic acid. Clinical presentation suggested bilateral conjunctivitis, but treatment with levofloxacin eye drops and acyclovir ophthalmic gel exacerbated the symptoms over 2 days, predominantly affecting the left eye. Ocular ultrasonography revealed thickening of the left eyeball wall with a "T" sign, while an orbital CT scan showed increased thickness of the left sclera. Treatment with methylprednisolone 80 mg intravenous infusion twice daily led to gradual symptom improvement and eventual resolution of inflammation. This report, based on a review of relevant literature, investigates the treatment and outcomes of zoledronic acid-induced scleritis, emphasizing the importance for clinicians to promptly identify and manage this rare and serious ocular adverse reaction.

Chronic Diffuse Sclerosing Osteomyelitis of the Mandible: The Use of Bisphosphonates as a Treatment for a Rare and Challenging Condition.

Chronic diffuse sclerosing osteomyelitis is a very rare condition, described as a non-suppurative, inflammatory disease of the bone and characterized by a proliferative endosteal reaction, which clinically reveals itself with cyclic pain of the jaw and swelling. We reported two clinical cases, where patients suffered recurrent swelling and pain at the mandible irradiating to the preauricular area, denying any previous trauma or significant medical history. Odontogenic causes were excluded. An initial treatment with antibiotics and NSAIDs temporarily relieved the symptoms without complete resolution, prompting further investigations. After a comprehensive array of diagnostic tools (X-rays, CT scans, scintigraphy, bone biopsy, serum markers), both patients were diagnosed with chronic diffuse sclerosing osteomyelitis of the mandible. Bisphosphonates (clodronate and zolendronate) with different treatment schemes were used to treat the condition, until a full recovery from symptoms was reported. Bisphosphonates could therefore represent an effective option in managing this rare but impactful condition. Further research is warranted to better understand the underlying mechanisms of the disease and to optimize treatment strategies.

Platelet-Rich Fibrin Treatment Evaluation in Patients with Medication-Related Osteonecrosis of the Jaw and Osteoradionecrosis.

Background. Medication-related osteonecrosis of the jaw (MRONJ) and osteoradionecrosis (ORN) are associated with severe disability and continuous pain, both of which are very difficult to control. This study aims to evaluate the outcome of platelet-rich fibrin (PRF) treatment compared to iodoform gauze packing and the primary suture of oral mucosa in patients with both MRONJ and ORN. Methods. Patients suffering from MRONJ and ORN who were treated in the Oral and Maxillofacial Surgery Clinic of Cluj-Napoca in the last 10 years were selected for this study from the hospital database. Results. PRF treatment proved to be a reliable method to help heal the necrotic bone sites. High-ASA risk patients and immunosuppressed patients are more prone to recurrence and persistent signs and symptoms. Intravenous bisphosphonates produce more intense symptomatology compared to oral administration. The posterior mandible is more difficult to treat compared to other sites. Conclusions. The quality of life of MRONJ and ORN patients may be improved by a protocol that reduces pain and hospitalization.

Osteonecrosis of the Jaw Associated with Bisphosphonates Infusion for Treatment of Plasma Cell Myeloma-A Retrospective Observational Study of Northern Portuguese Population.

Objectives: To verify medication-related osteonecrosis of the jaw (MRONJ) frequency among patients with plasma cell myeloma (PCM) that had been treated with bisphosphonates, to identify predisposing factors that could influence the development of osteonecrosis. Methods: This observational retrospective study was performed at the Department of Hematology of Hospital Center of Porto (CHUP), Portugal. Results: The study population (n = 112) had a 15.2% (n = 17) prevalence of osteonecrosis. Clinically, bone exposure was the most frequently observed sign, present in 100% (n = 17) of the patients, followed by inflammation in 82.4% (n = 14), orofacial pain in 70.6% (n = 12), suppuration in 47.1% (n = 8), and intra or extra-oral fistula in 17.6% (n = 3) of the cases. The most frequent triggering local factor was dental extraction (82.4%). There was a dependence between the presence of extractions and the development of MRONJ (p < 0.001) but not with the time elapsed from the initiation of infusions with BPs and dental extractions (p = 0.499). In the sample of patients with multiple myeloma (MM), 13.8% were found to be more likely to develop MRONJ after an extraction. Conclusions: The most common local predisposing factor was dental extraction. No dependence was observed between the development of osteonecrosis and the time elapsed from the beginning of treatment with bisphosphonates infusions to surgical procedures.

Evaluating calcium channel blockers and bisphosphonates as otoprotective agents in cochlear implantation hearing preservation candidates.

OBJECTIVES: Evaluate potential effects of calcium channel blockers (CCB) and bisphosphonates (BP) on residual hearing following cochlear implantation. METHODS: Medications of 303 adult hearing preservation (HP) candidates (low frequency pure tone average [LFPTA] of 125, 250, and 500 Hz ≤80 dB HL) were reviewed. Postimplantation LFPTA of patients taking CCBs and BPs were compared to controls matched by age and preimplantation LFPTA. RESULTS: Twenty-six HP candidates were taking a CCB (N = 14) or bisphosphonate (N = 12) at implantation. Median follow-up was 1.37 years (range 0.22-4.64y). Among subjects with initial HP, 29% (N = 2 of 7) CCB users compared to 50% (N = 2 of 4) controls subsequently lost residual hearing 3-6 months later (OR = 0.40, 95% CI = 0.04-4.32, p = 0.58). None of the four BP patients with initial HP experienced delayed loss compared to 50% (N = 2 of 4) controls with initial HP (OR = 0.00, 95% CI = 0.00-1.95, P = 0.43). Two CCB and one BP patients improved to a LFPTA <80 dB HL following initial unaided thresholds that suggested loss of residual hearing. DISCUSSION: There were no significant differences in the odds of delayed loss of residual hearing with CCBs or BPs. CONCLUSION: Further investigation into potential otoprotective adjuvants for maintaining residual hearing following initial successful hearing preservation is warranted, with larger cohorts and additional CCB/BP agents.

The effect of black cohosh extract and risedronate coadministration on bone health in an ovariectomized rat model.

Preparations of black cohosh extract are sold as dietary supplements marketed to relieve the vasomotor symptoms of menopause, and some studies suggest it may protect against postmenopausal bone loss. Postmenopausal women are also frequently prescribed bisphosphonates, such as risedronate, to prevent osteoporotic bone loss. However, the pharmacodynamic interactions between these compounds when taken together is not known. To investigate possible interactions, 6-month-old, female Sprague-Dawley rats underwent bilateral ovariectomy or sham surgery and were treated for 24 weeks with either vehicle, ethinyl estradiol, risedronate, black cohosh extract or coadministration of risedronate and black cohosh extract, at low or high doses. Bone mineral density (BMD) of the femur, tibia, and lumbar vertebrae was then measured by dual-energy X-ray absorptiometry (DEXA) at weeks 0, 8, 16, and 24. A high dose of risedronate significantly increased BMD of the femur and vertebrae, while black cohosh extract had no significant effect on BMD individually and minimal effects upon coadministration with risedronate. Under these experimental conditions, black cohosh extract alone had no effect on BMD, nor did it negatively impact the BMD-enhancing properties of risedronate.

Influence of the use of bisphosphonates on the development of postextraction sequelae: scoping review with mapping evidence of in vivo studies.

OBJECTIVE: To map the current scientific landscape regarding the association/causality of medication-related osteonecrosis of the jaw (MRONJ) after tooth extraction under bisphosphonate (BF) therapy to identify knowledge gaps and guide future research. DATA: This review used the PCC strategy (P = Patient; C = Concept; C = Context). SOURCES: The MEDLINE/PubMed, Scopus, Web of Science/Clarivate Analytics, and gray literature databases were used. STUDY SELECTION: Searches were conducted by two independent reviewers until April 2024. Studies involving prior BF use and tooth extraction in humans or animals were included. Among the 176 studies, 73 (41.4%) were in animals, and 103 (58.5%) were in humans. Brazil led in animal studies (n=14; 19.1%), while Italy led in human studies (n=14; 13.6%). Zoledronic acid was the most cited BF (79.4% in animals; 34.9% in humans), with intravenous administration being most frequent (38.3% in animals; 35.9% in humans). The mandible was the main extraction site (n=36 in animals; n=41 in humans). In 91.7% of the animal studies, sequelae compatible with osteonecrosis signs and symptoms were observed, with bone necrosis being most common (n=39; 53.4%). In humans, 93.2% of studies presented 239 sequelae, with bone necrosis (n=53; 22.1%) being the most cited. The main location of sequelae was the mandible (n=36 in animals; n=41 in humans). CONCLUSIONS: Animal studies highlighted bone exposure, notably using murine models, with a significant Brazilian contribution. In human studies, bone necrosis was the main sequela of MRONJ, which has been reported by researchers in the Italy. CLINICAL SIGNIFICANCE: These findings underscore the importance of careful consideration and monitoring of patients who have a history of bisphosphonate use and who are undergoing tooth extraction, highlighting the potential risk of MRONJ.

Role of bisphosphonates in hypertrophic osteoarthropathy: a systematic review.

BACKGROUND: The role of bisphosphonates (BP) in hypertrophic osteoarthropathy (HPOA) is unclear. We presented a case of primary HPOA and performed a systematic review of literature on the effect of BP on treatment response in primary and secondary HPOA. METHODS: The study was prospectively registered in PROSPERO (CRD42022343786). We performed a PubMed literature search that restricted to the English language. We included patients diagnosed with primary or secondary HPOA who received BP. The primary endpoint assessed was the effectiveness of BP on response to pain or arthritis. Secondary outcomes included timing, degree, and duration of response, comparison to other HPOA therapies, impact of BP on radiology, bone scan, bone turnover markers, and adverse effects of BP. RESULTS: Literature search retrieved only case reports. Forty-five patients (21 primary, 24 secondary HPOA) had received BP. Majority(88.3%) experienced improvement in pain or arthritis. Response was gradual for primary HPOA and within a median of 3 to 7 days for secondary HPOA after treatment with BP. Most patients had reduced bone scan uptake after BP. When other HPOA therapies were tried, half responded to BP after not having previously responded to other therapies, while a third received the treatments concurrently, making it difficult to attribute treatment response to a drug. Reporting of other secondary outcomes was very heterogenous and qualitative to draw conclusions. No major adverse effects have been reported for BP in HPOA. CONCLUSION: Bisphosphonates provide an effective and safe treatment option for primary and secondary HPOA. However, there is a lack of randomized controlled trials.

Increased risk of hypocalcemia with decreased kidney function in patients prescribed bisphosphonates based on real-world data from the MID-NET® in Japan: a new-user cohort study.

BACKGROUND: In the post-marketing stage, cases of hypocalcemia associated with bisphosphonate preparations (BPs) have been reported in patients with decreased kidney function, despite warning against use of BPs in such patients in the package insert (PI) of Japan. The purpose of this study was to investigate the safety of BPs in patients with decreased kidney function. METHODS: The cohort study was conducted in patients with osteoporosis and newly prescribed bisphosphonate utilizing real-world data from MID-NET® in Japan. The adjusted hazard ratios (aHRs) for hypocalcemia (a corrected serum Ca level < 8.00 mg/dL) relative to the normal group were calculated in each decreased kidney function group (mild, moderate or severe group). RESULTS: A total of 14,551 patients were included in the analysis, comprising 2,601 (17.88%) with normal (eGFR ≥ 90 mL/min/1.73m2), 7,613 (52.32%) with mild (60 ≤ eGFR < 90 mL/min/1.73m2), 3,919 (26.93%) with moderate (30 ≤ eGFR < 60 mL/min/1.73m2), and 418 (2.87%) with severe kidney function (eGFR < 30 mL/min/1.73m2). The aHRs (95% confidence interval) for hypocalcemia were 1.85 (0.75-4.57), 2.30 (0.86-6.21), and 22.74 (8.37-61.78) in the mild, moderate, and severe groups, respectively. The increased risk of hypocalcemia depending on kidney function was also observed even when calculating the aHR for each specific BP such as alendronate sodium hydrate, minodronic acid hydrate, and sodium risedronate hydrate. Furthermore, similar results were obtained in the sensitivity analysis by altering the outcome definition to a 20% or more reduction in corrected serum Ca level from the baseline, as well as when focusing on patients with more than one laboratory test result per 30 days during the follow-up period. CONCLUSIONS: These findings suggest that the risk of hypocalcemia during BP prescription is higher in patients with decreased kidney function, particularly those with severely decreased kidney function. The quantitative real-world evidence on the safety risk of BPs obtained in this study has led to the PI revision describing a relationship between hypocalcemia risk and decreased kidney function as a regulatory action in Japan and will contribute to promoting the proper use of BPs with appropriate risk management in clinical practice.

Fatality owing to pulmonary hemorrhage following pamidronate disodium administration in a neonate with osteogenesis imperfecta type 2: A case report.

We report the case of a patient with osteogenesis imperfecta (OI) who developed pulmonary hemorrhage 4 d after pamidronate disodium (PA) administration, despite a relatively stable respiratory status. Bisphosphonates are introduced to reduce osteoclast activity and are now widely used in patients with OI. Bisphosphonates are typically well-tolerated in children, and the standard of care involves cyclic intravenous administration of PA. However, in practice, there is limited experience with the use of PA for severe OI during the neonatal period, and its safety remains uncertain. This report aimed to describe the respiratory events potentially associated with PA in a neonatal patient with OI type 2, suggesting that serious life-threatening complications of pulmonary hemorrhage may occur after PA administration. Further studies are required to assess the relationship between pulmonary hemorrhage and PA administration, aiming to enhance prophylaxis measures.

Zoledronic Acid Supplementation With Excision of a Giant Cell Tumor of the Distal End Radius to Prevent Recurrence: A Case Report.

Giant cell tumors are benign yet locally aggressive neoplasms commonly observed in the distal radius, exhibiting higher recurrence rates compared to other tumor types. This study presents a case involving a 50-year-old farmer who presented with swelling at the distal end of his wrist. The patient underwent treatment involving intralesional curettage and supplementation with zoledronic acid, resulting in a significant reduction in the tumor's potential for recurrence. This approach aims to achieve an optimal balance between functional outcomes and disease management in the majority of cases. While this strategy proves effective in most instances, there may be scenarios where resection becomes imperative due to the severity of the disease, ensuring adequate disease clearance. In such circumstances, judicious decision-making coupled with an appropriate treatment plan is crucial to guarantee a satisfactory outcome, even in the face of challenges.