Comparison of Postoperative Results With Prognostic Nutritional Index for Lumbar Disc Herniation.

INTRODUCTION: The prognostic nutritional index (PNI) is an immune-nutritional index simply provided by a blood test. We retrospectively compared the postoperative outcomes of patients with lumbar disc herniation divided into two groups according to the PNI. MATERIALS AND METHODS: Seventy-three patients who underwent surgery at our hospital were included in the study. All patients had herniation between one of the L3/4, L4/5, or L5/S intervertebral discs and underwent one posterior lumbar interbody fusion. These patients were divided into two groups: patients with a PNI of <50 (poorly nourished (PN) group) and patients with a PNI of ≥50 (well-nourished (WN) group). Evaluation items included patient background characteristics, operative time, blood loss, postoperative complications, and length of hospital stay. RESULTS: The results showed that the body mass index was significantly higher in the WN group than in the PN group (p=0.0221). The rates of collagen disease, steroid use, and postoperative complications were significantly higher (p=0.0475, p=0.0073, and p=0.0211, respectively) and the length of hospital stay was significantly longer (p=0.021) in the PN group than in the WN group. CONCLUSION: In conclusion, this study indicates that postoperative complications and the length of hospital stay are significantly worse in PN patients than in WN patients.

The Impact of Reduced Skeletal Muscle Mass on Patients with Knee Osteoarthritis.

Although several studies have suggested a possible association between sarcopenia and knee osteoarthritis (OA) in the elderly, there remains no definitive evidence. Recently, however, the serum creatinine/cystatin C ratio (sarcopenia index: SI) was reported to correlate with skeletal muscle mass. The present retrospective study therefore investigated the impact of reduced skeletal muscle mass on advanced knee OA using SI. In 55 individuals scheduled for knee osteotomy or knee arthroplasty, correlations between SI and patient-reported outcomes such as the Knee Society Score (KSS), Knee Injury and Osteoarthritis Outcome Score (KOOS), and Oxford Knee Score (OKS) were explored. Significant associations were found between SI and the KSS functional activity score (ß=0.37; p=0.022), KOOS subscale for activities of daily living (ß=0.42; p=0.0096), and OKS (ß=0.42; p=0.0095). This study underscores the role of reduced muscle mass in functional outcomes and introduces SI as a valuable marker for assessing muscle loss in knee OA patients.

Effect of Acridine Orange and Zoledronic Acid on Bone Metastasis in Renal Cell Carcinoma.

BACKGROUND/AIM: The increasing incidence of renal cell carcinoma (RCC) and its associated bone metastasis pose challenges in surgical interventions, warranting the exploration of novel therapeutic approaches. Therefore, this study aimed to assess the impact of hematogenously administering acridine orange (AO) alone and in combination with zoledronic acid (ZA) on bone metastasis in RCC. MATERIALS AND METHODS: RENCA cells (1.0×106 cells/10 µl) were directly injected into the right femur of male BALB/c mice. The mice were categorized into four groups based on the applied therapeutic intervention and were euthanized after five weeks. Micro-computed tomography was performed to quantify the extent of periosteal reaction, indicative of bone metastasis, along the entire length of the femur. Tumor weight and volume were measured at euthanization. Hematoxylin and eosin staining was used to examine the extent of tumor development in the bone. Apoptotic cell, osteoclast, and vascular endothelial growth factor (VEGF)-positive cell counts were assessed using TdT-mediated dUTP-biotin nick end labeling, tartrate-resistant acid phosphatase staining, and VEGF staining, respectively. RESULTS: The periosteal reaction was significantly reduced in the intervention groups compared to the control group (p<0.05). The apoptotic cell numbers in the intervention groups surpassed that in the control group (p<0.05), whereas those of osteoclasts and VEGF-positive cells in the intervention groups were lower than those in the control group (p<0.05). CONCLUSION: AO hinders bone metastasis progression in RCC, and combination therapy with ZA may be more effective than AO administration alone.

Development of a New Focal Mouse Model of Bone Metastasis in Renal Cell Carcinoma.

BACKGROUND/AIM: Developing animal models of bone metastasis in renal cell carcinoma (RCC) is challenging as immunodeficient mice are required. The aim of this study was to develop a simple immune model of RCC bone metastasis. MATERIALS AND METHODS: RENCA tumor cells were injected into the right femurs of BALB/c mice. Sixty mice were grouped into each twenty-mouse group according to the tumor cell concentration, and the presence or absence and extent of bone metastasis in the total length of the femur were compared using hematoxylin and eosin staining of the excised tissues. RESULTS: Bone metastasis was significantly higher in the high concentration group than in the other groups (p<0.05), with 10 mice developing bone metastasis at two weeks and nine mice developing bone metastasis at three weeks. The extent of bone metastasis was significantly greater in the high concentration group than in the other groups (p<0.05). Multiple logistic regression analysis was performed to examine the factors influencing bone metastasis, and only the high concentration was a significant factor (p<0.05). CONCLUSION: We developed a normal immunity mouse model of local bone metastasis from RCC. This model could prove valuable for research into the treatment of bone metastases in RCC.

A Comparison of Hidden Blood Loss Between Multilevel Posterior Lumbar Interbody Fusion and Lateral Lumbar Interbody Fusion in Adult Spinal Deformity Patients.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: This study aimed to compare transfusion and blood loss volumes, particularly hidden blood loss volume, in adult spinal deformity patients undergoing lateral lumbar interbody fusion (LLIF) and posterior lumbar interbody fusion (PLIF). Corrective surgery for adults with spinal deformity patients can be performed via the traditional posterior approach (PLIF) or minimally invasive lateral approach (LLIF). LLIF is associated with longer or comparable operation times and lower intraoperative blood loss. However, hidden blood loss has not been compared between the two procedures. METHODS: We compared hidden blood loss and other blood loss volumes, transfusion volume, operation time, and radiographic surgical outcomes between LLIF patients (n = 71) and PLIF patients (n = 33) who underwent surgery in our institution from September 2011 to June 2018. All patients provided informed consent in accordance with the Declaration of Helsinki. Institutional ethics committee conducted this study approval was obtained. RESULTS: Transfusion volume and intraoperative and total blood loss volumes were significantly higher in the PLIF group. Operation time and HBL did not significantly differ. The hidden blood loss-to-intraoperative blood loss ratio was significantly higher in the LLIF group (113% vs 60%; P = .004). Radiographic measures of outcome were significantly better after surgery than before in both groups. CONCLUSIONS: Although intraoperative blood loss was less with LLIF than PLIF, HBL was similar between the approaches. Patients undergoing LLIF should be followed closely for postoperative anemia even if intraoperative blood loss is low.

Two Cases of Degenerative Cervical Spondylotic Myelopathy in Adults with Athetoid and Dystonic Cerebral Palsy.

BACKGROUND Patients with athetoid and dystonic cerebral palsy (ADCP) may develop degenerative changes in the cervical spine that can aggravate their neurological symptoms in adulthood. This report is of 2 cases of ADCP associated with degenerative cervical spondylotic myelopathy in a 39-year-old woman and a 52-year-old man, requiring different surgical treatments. CASE REPORT Case 1. The patient was a 39-year-old woman who had fallen down 7 years before surgery and had since been walking with a cane. Her gait disturbance had worsened in the 2 years prior to surgery, and numbness in her upper limbs appeared. In the year before surgery, spasticity and numbness in the lower limbs worsened, and fine motor impairment also appeared. Because of mild involuntary movements of the neck, cervical laminoplasty from C3 to C6 was performed, and her symptoms remained stable until the last follow-up 4.5 years after surgery. Case 2. The patient was a 52-year-old man who had fallen down 7 years before surgery, resulting in transient limb weakness. In the year before surgery, he had developed fine motor impairment. He subsequently developed gait disturbance and requested cervical surgery. Because of involuntary movements involving the neck and trunk, he underwent cervical posterior fusion from C2 to T1. Six months after surgery, the gait disturbance had improved. CONCLUSIONS This report describes 2 adults with a history of ADCP since birth and highlights that degenerative changes of the cervical spine can occur at a relatively early age in adulthood, requiring an individualized approach to management.

Neurological Analysis Based on the Terminal End of the Spinal Cord and the Narrowest Level of Injured Spine in Thoracolumbar Spinal Injuries.

This study aimed to clarify neurological differences among the epiconus, conus medullaris, and cauda equina syndromes. Eighty-seven patients who underwent surgery for acute thoracolumbar spinal injuries were assessed. We defined the epiconus as the region from the terminal end of the spinal cord to the proximal 1.0 to 2.25 vertebral bodies, the conus medullaris as the region proximal to < 1.0 vertebral bodies, and the cauda equina as the distal part of the nerve roots originating from the spinal cord. On the basis of the distance from the terminal end of the spinal cord to the narrowest level of the spinal canal, the narrowest levels were ordered as follows: the epiconus followed by the conus medullaris and cauda equina. The narrowest levels were the epiconus in 22 patients, conus medullaris in 37 patients, and cauda equina in 25 patients. On admission, significantly more patients had a narrowed epiconus of Frankel grades A-C than a narrowed cauda equina. At the final follow-up, there were no significant differences in neurological recovery among those with epiconus, conus medullaris, or cauda equina syndrome. Anatomically classifying the narrowest lesion is useful for clarifying the differences and similarities among these three syndromes.

Effects of Soft Tissue Sarcoma and Doxorubicin on Bone Metabolism in Mice.

BACKGROUND/AIM: This study aimed to evaluate the effects of doxorubicin (Dox) on bone microstructure and metabolism in a mouse model of soft tissue sarcoma. MATERIALS AND METHODS: CCRF S-180II cells (2-4×105 cells/0.2 ml) were injected subcutaneously into the back of mice. The mice were divided into four groups according to tumor and treatment status and were reared and sacrificed after 2 or 4 weeks. Micro-computed tomography (CT) was performed to calculate the architecture of the femoral bone. The proximal tibia was double stained with tartrate-resistant acid phosphatase (TRACP) and alkaline phosphatase (ALP), and bone morphometry was performed. RESULTS: Trabecular bone mass was significantly reduced in the Sarcoma and Sarcoma+Dox groups. Cortical bone thickness was reduced in the DOX group, with a stronger effect observed in the Sarcoma+Dox group. In bone morphometry, osteoclast number at the bone surface (Oc.N/BS) was significantly lower in the Dox, Sarcoma, and Sarcoma+Dox groups than in the Control group at 2 weeks. The osteoblast surface at the bone surface (Ob.S/BS) was significantly lower in the Dox and Sarcoma groups than in the Control group at 2 weeks. At 4 weeks, the differences were smaller for both Oc.N/BS and Ob.S/BS. CONCLUSION: The use of doxorubicin alone worsened the cortical bone structure; however, the presence of both soft-tissue sarcoma and doxorubicin use worsened both cortical and trabecular bone structures from an early stage.

Intravascular Administration of Acridine Orange and Zoledronate in a Bone Metastasis Model of Breast Cancer.

BACKGROUND/AIM: This study evaluated the effect of haematogenous administration of acridine orange (AO) alone and in combination with zoledronate (ZOL) on bone metastases. MATERIALS AND METHODS: E0771 cells (1.0×105 cells/10 µl) were injected directly into the right femur of female mice. The mice were divided into five groups according to treatment (drugs and irradiation) and were reared and sacrificed after 6 weeks. Micro-computed tomography (µCT) was performed to calculate the destruction rate of the femur bone. We measured tumour weight and volume at sacrifice and performed terminal deoxynucleotidyl transferase dUTP Nick-End Labelling staining of tumours. RESULTS: At 4 weeks, the bone destruction rate was lower in the AO+ZOL group than in the radiation group. At 6 weeks, the AO+ZOL group had a lower bone destruction rate than the control and radiation groups; the ZOL group had a lower rate than the radiation group. The AO and AO+ZOL groups had suppressed tumour weight and volume compared to the control and radiation groups. The number of extraosseous apoptotic cells was higher in the AO+ZOL group than in all other groups except the AO group. CONCLUSION: In a model of local bone metastasis of breast cancer, haematogenous administration of AO reduced tumour size and more so when combined with ZOL.

Degenerative Lumbar Spondylolisthesis Patients With Movement-related Low Back Pain Have Less Postoperative Satisfaction After Decompression Alone.

STUDY DESIGN: Retrospective analysis of prospectively collected multicenter observational data. OBJECTIVE: The aim was to examine the preoperative factors affecting postoperative satisfaction following posterior lumbar interbody fusion (PLIF) and microendoscopic muscle-preserving interlaminar decompression (ME-MILD) in patients with degenerative lumbar spondylolisthesis (DLS). SUMMARY OF BACKGROUND DATA: The technique involved in DLS surgery may either be decompression alone or decompression-fixation. Poor performance may occur after either of these surgical treatments. The author hypothesized that evaluating the correlation between preoperative quality of life and postoperative performance would aid in determining the optimal procedure. MATERIALS AND METHODS: This study included 138 patients who underwent surgery for 1-level mild DLS. The authors performed PLIF for 79 patients and ME-MILD for 59 patients. When the satisfaction subscale of the Zurich Claudication Questionnaire exceeded 2 points, postoperative satisfaction was considered poor. The clinical characteristics were investigated. Responses to preoperative health-related quality of life questionnaires, such as the Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ), short form-36 health survey (SF-36), and visual analog scale, were compared between the satisfied and unsatisfied groups. RESULTS: In the PLIF group, no endogenous factors influenced postoperative satisfaction. The ME-MILD cohort's satisfied and unsatisfied patients differed significantly in terms of preoperative lumbar spine dysfunction ( P <0.001) items of the JOABPEQ, role physical ( P =0.03), and role emotional ( P =0.03) items of the SF-36. A strong correlation ( r =-0.609 P =0.015) was found between preoperative lumbar spine dysfunction and postoperative satisfaction. CONCLUSIONS: In the ME-MILD group, preoperative lumbar spine function was correlated with postoperative satisfaction. Decompression alone may be ineffective in cases with decreased lumbar spine function prior to surgery. The degree of low back pain on movement should be considered before selecting the surgical method. LEVEL OF EVIDENCE: 3.

Development of New Mouse Breast Cancer Model of Local Bone Metastasis and Verification Using Bisphosphonates.

BACKGROUND/AIM: Local tumor injection models require complicated procedures. The purpose was to establish a simple local bone metastasis model using normal mice, and to study the usefulness of the model with bisphosphonates (BP). MATERIALS AND METHODS: This study used a versatile C57BL/6 mouse model and E0771 cells. Tumor cells were injected into the right femur. Mice were divided into groups depending on the concentration of cells injected and the use of BP or not. The degree of bone destruction between the different conditions was compared using micro-computed tomography (µCT). RESULTS: Bone destruction was confirmed in four mice in the high-concentration group at 3 weeks, and in all other mice at 4 and 6 weeks. At 6 weeks post-injection, bone destruction was significantly suppressed in the BP group (p<0.05). CONCLUSION: We created a breast cancer mouse model of local bone metastasis. Zoledronate showed the same usefulness as in previous models. It may be an effective model for evaluating treatments for bone metastasis.

Chronic atlantoaxial rotatory fixation with neurofibromatosis type I: A case report.

BACKGROUND: Atlantoaxial rotatory fixation (AARF) can be caused by infection, rheumatoid arthritis, surgery of head and neck, and congenital diseases. Type 1 neurofibromatosis (NF-1) is often associated with various musculoskeletal diseases, but few reports have described AARF with NF-1. Here, we report the success of a closed reduction and halo fixation utilized to treat chronic AARF with NF-1 in a 7-year-old female. CASE DESCRIPTION: A 7-year-old female with NF-1 presented with a 2-month history of torticollis and neck pain. C2 facet deformity had previously been identified on computed tomography (CT) before the onset of neck pain. Cervical radiography and CT showed AARF classified Fielding's Type I and Ishii's Grade II. Following 2 weeks of cervical traction, a closed reduction was followed by halo fixation that was utilized for 2 months. The patient fully recovered cervical range of motion following halo vest removal 4 months later. Further, the follow-up CT documented a normal atlantoaxial joint despite residual C2 facet deformity. In addition, no recurrence was evident 2 years later. CONCLUSION: Halo fixation for chronic AARF with NF-1 proved effective. C2 facet deformity associated with NF-1 might have contributed to the onset of AARF.

Impact of a Specialized Outpatient Clinic on Bone Metastasis and Its Burden on Spine Surgeons.

BACKGROUND/AIM: It is important to perform early intervention on bone metastases using multidisciplinary approaches, however it is difficult to hold frequent meetings between patients and clinicians. We aimed to evaluate the usefulness of a specialized outpatient clinic on bone metastasis, instead of the multidisciplinary approach currently in practice. PATIENTS AND METHODS: We included 31 patients with vertebral metastases of various carcinomas, undergoing surgical treatment by spine surgeons. We divided the patients into two groups before and after their visit to the specialized outpatient clinic (pre and post groups), and compared their clinical characteristics. RESULTS: The post group demonstrated a longer period from consulting the spine surgeon to the surgery than the pre group (p=0.0129). A multivariate logistic regression analysis revealed that the period from spine surgeon consultation to surgery was significantly associated with a specialized outpatient clinic visit (p=0.0460). CONCLUSION: Specialized outpatient clinics on bone metastasis could possibly reduce the burden on spinal surgeons.

Herniation of the cauda equina into the facet joint through a pseudomeningocele: A case report and literature review.

BACKGROUND: Incidental durotomy is a well-known complication of spinal surgery. It can lead to persistent cerebrospinal fluid leakage resulting in significant secondary complications. Here, we present a case in which the cauda equina herniated into a pseudomeningocele that penetrated a facet joint, leading to lower extremity radiculopathy warranting surgical correction. CASE DESCRIPTION: One year ago, a 67-year-old male underwent a partial left L4-L5 laminectomy. At surgery, a durotomy was repaired with a nylon suture and reinforced with a fat patch. He subsequently presented with severe left lower extremity radiculopathy and a partial cauda equina syndrome. On MR, the cauda equina had herniated into a pseudomeningocele that penetrated the left facet joint. Once the defect was repaired at surgery, the patient's symptoms improved. CONCLUSION: It is critical to correctly repair an intraoperative durotomy to avoid further neurological deficits that may include cauda equina herniation into pseudomeningoceles penetrating facet joints.

Thin Cervical Spinal Cord Between Ossifications of the Ligamentum Flavum and the Posterior Longitudinal Ligament: Case Report and Literature Review.

BACKGROUND: Cervical ossification of the ligamentum flavum (OLF) is a rare condition; however, the coexistence of OLF and ossification of the posterior longitudinal ligament (OPLL) is extremely uncommon. These can exist simultaneously and cause thinning of the cervical spinal cord. Sufficient decompression, dural ossification, semispinalis dissection, and postoperative kyphosis were evaluated. We report the successful treatment of coexisting cervical OLF and OPLL. CASE DESCRIPTION: A 70-year-old man had been experiencing weakness in the left knee and clumsiness in the left hand for 6 months. Hemiparesis was considered; however, magnetic resonance imaging revealed a cervical spinal lesion. Hence a spine surgeon diagnosed the patient with severe stenosis with OLF at the C2-C3 levels and OPLL at the C2-C4 levels. The patient presented with spastic gait and left-hand motor weakness. Computed tomography scan revealed the disappearance of the black line, indicating dural ossification surrounding the OLF. OPLL was observed in 61.5% of the C2 spinal canal. The K-line was (-); however, the alternative K-line between the C1 and C7 level was (+). Posterior laminectomy at the C2-C3 levels and laminoplasty at the C4-C7 levels with muscle preservation resulted in sufficient decompression. The patient's symptoms improved, and cervical alignment was maintained 2 years after surgery. CONCLUSIONS: An alternative K-line comprised successful treatment for coexisting cervical OLF and OPLL. Surgeons must evaluate the severity of adhesion, damage of the paraspinal muscles, and necessity of posterior corrective surgery along with the patient's comorbidities and possible postoperative complications.

Risk Factor for Poor Patient Satisfaction After Lumbar Spine Surgery in Elderly Patients Aged Over 80 years.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To clarify the poor patient satisfaction after lumbar spinal surgery in elderly patients. SUMMARY OF BACKGROUND DATA: As the global population continues to age, it is important to consider the surgical outcome and patient satisfaction in the elderly. No studies have assessed patient satisfaction in elderly patients undergoing surgical treatment and risk factors for poor satisfaction in elderly patients after lumbar spinal surgery. MATERIALS AND METHODS: A retrospective multicenter survey was performed in 169 patients aged above 80 years who underwent lumbar spinal surgery. Patients were followed up for at least 1 year after surgery. We assessed patient satisfaction from the results of surgery by using a newly developed patient questionnaire. Patients were assessed by demographic data, surgical procedures, complications, reoperation rate, pain improvement, and risk factors for poor patient satisfaction with surgery for lumbar spinal disease. RESULTS: In total, 131 patients (77.5%, G-group) were satisfied and 38 patients (22.5%, P-group) were dissatisfied with surgery. The 2 groups did not differ significantly in baseline characteristics and surgical data. Postoperative visual analog scale score for low back pain and leg pain were significantly higher in the P-group than in the G-group (low back pain: G-group, 1.7±1.9 vs. P-group, 5.2±2.5, P<0.001; leg pain: G-group, 1.4±2.0 vs. P-group, 5.5±2.6, P<0.001). Multivariate regression analysis revealed that postoperative vertebral fracture (P=0.049; odds ratio, 3.096; 95% confidence interval, 1.004-9.547) and reoperation (P=0.025; odds ratio, 5.692; 95% confidence interval, 1.250-25.913) were significantly associated with the patient satisfaction after lumbar spinal surgery. CONCLUSIONS: Postoperative vertebral fracture and reoperation were found to be risk factors for poor patient satisfaction after lumbar spinal surgery in elderly patients, which suggests a need for careful treatment of osteoporosis in addition to careful determination of surgical indication and procedure in elderly patients. LEVEL OF EVIDENCE: Level III.

Cervical meningioma resection including the inner dura through an open-door laminoplasty using hydroxyapatite spacers: A case report.

BACKGROUND: The ideal surgery for spinal cord tumors is complete resection to prevent recurrence. However, it should be accomplished safely/effectively without risking increased morbidity. Here, we report a cervical meningioma that was totally resected, including the inner dura, through a laminoplasty performed with hydroxyapatite (HA) spacers. CASE DESCRIPTION: A 61-year-old Asian male presented with a symptomatic intradural extramedullary C4-C6 cervical meningioma. At surgery, this required resection of the inner dural layer through an open-door laminoplasty. Preservation of the outer dural layer facilitated a watertight closure and the avoidance of a postoperative cerebrospinal fluid (CSF) fistula. Notably, the laminoplasty utilized HA spacers which were magnetic resonance (MR) compatible allowing for future follow-up studies to evaluate for tumor recurrence. At 5-year follow-up, the tumor had not recurred, the patient was asymptomatic, and alignment was maintained. CONCLUSION: Gross total resection of an intradural extramedullary C4-C6 cervical meningioma was performed with removal of just the inner dural layer. Preservation of the outer dural layer allowed for a watertight closure and the avoidance of a postoperative CSF leak. Further, laminoplasty using HA spacers allowed for successful tumor resection, adequate fusion/stabilization, while not interfering with future MR studies (e.g., HA MR compatible).

Diagnosis and Surgical Treatment of Thoracic Dorsal Arachnoid Web: A Report of Two Cases.

INTRODUCTION: An arachnoid web (AW) is a relatively rare disease and shows clinical symptoms and radiological findings similar to those of an arachnoid cyst (AC) or spinal cord herniation (SCH). Since the operative procedures for an AW are generally different from those intrathecal disorders, correct preoperative differential diagnosis is important. The purposes of this study were to report the usefulness of magnetic resonance imaging (MRI) and computed tomography (CT) myelography for diagnosing AW and to show the histological findings and clinical results. Case Description. Two patients, a 79-year-old man and a 43-year-old woman, are presented. The primary diagnoses were AC with ossification of the ligamentum flavum and epidural hematoma, respectively, in previous hospitals. They were finally diagnosed by the characteristic MRI and CT myelogram finding called the "scalpel sign." Histological findings showed epithelial cells and fibrous tissue derived from arachnoid tissues and microcalcifications. After surgery, the scalpel sign has vanished, and aggravation of their symptoms was prevented. CONCLUSION: An AW is refractory, but early detection by MRI and CT myelography and early treatment improve outcomes after surgery.

Pharmacologic treatment of GERD: Where we are now, and where are we going?

The introduction of acid inhibition in clinical practice has revolutionized the management of acid-related diseases, leading to the virtual abolition of elective surgery for ulcer disease and relegating antireflux surgery to patients with gastroesophageal reflux disease (GERD) not adequately managed by medical therapy. Proton pump inhibitors (PPIs) are the antisecretory drugs of choice for the treatment of reflux disease. However, these drugs still leave some unmet clinical needs in GERD. PPI-refractoriness is common, and persistent symptoms are observed in up to 40-55% of daily PPI users. Potassium-competitive acid blockers (P-CABs) clearly overcome many of the drawbacks and limitations of PPIs, achieving rapid, potent, and prolonged acid suppression, offering the opportunity to address many of the unmet needs. In recent years, it has been increasingly recognized that impaired mucosal integrity is involved in the pathogenesis of GERD. As a consequence, esophageal mucosal protection has emerged as a new, promising therapeutic avenue. When P-CABS are used as add-on medications to standard treatment, a growing body of evidence suggests a significant additional benefit, especially in the relief of symptoms not responding to PPI therapy. On the contrary, reflux inhibitors are considered a promise unfulfilled, and prokinetic agents should only be used on a case-by-case basis.