Partial Clinical Response Research Articles

Evaluating the Benefits of Pelvic Floor Muscles Exercises Combined With Biofeedback Therapy for Improving Functional Urinary Incontinence in Children.

Pelvic floor muscles training (PFMT), with or without biofeedback (BF), is widely utilized as an alternative treatment for various refractory lower urinary tract dysfunctions in adults and children. This study aimed to compare the efficacy of PFMT alone versus in combination with BF on functional urinary incontinence (UI) in children. Medical records of children who had undergone pelvic floor rehabilitation for non-neuropathic intermittent UI from 2018 to 2022 were retrieved. Patients were categorized based on their treatment regimen. Group I had undergone standard urotherapy and PFMT, twice weekly for 5 weeks. Group II had undergone a similar 5-week treatment with addition of 10 BF sessions conducted at the end of each appointment. All children had been evaluated with kidney and bladder ultrasounds, uroflowmetry/EMG, and a 7-day voiding and bowel diary before and after treatment. Response to treatment was defined according to International Children's Continence Society (ICCS) protocols. A total of 32 patients (71.9% female) with a mean age of 8.4 ± 2.1 (range: 5-13) years were included in the analyses (each group N = 16). In group I, nine (56.2%) and two (12.5%) patients demonstrated complete (100% reduction in UI episodes) and partial (50%-100% reduction in UI episodes) clinical response, respectively. In group II, 11 (68.7%) and 3 (18.8%) patients showed complete and partial response, respectively. The two groups were not significantly different with regard to clinical response (p = 0.430). No significant difference was observed between the two groups in terms of enuresis, urgency, constipation, and uroflowmetry parameters. PFMT under the supervision of an expert physical therapist appears to be as effective as combined PFMT and BF in improving UI in children without underlying neurologic disease.

Effect of neoadjuvant chemotherapy on CD14 + CD16 + monocytes and soluble CD163 in Egyptian breast cancer patients

Neoadjuvant chemotherapy (NACT) influences the anticancer response by favourably altering the immune microenvironment. However, the effects of NACT on peripheral monocytes and their prognostic contribution to the NACT response have not yet been clarified. We aimed to evaluate the potential therapeutic responses and possible predictive value of double-positive (CD14 + CD16 +) monocytes and soluble CD163 (sCD163) in Egyptian breast cancer patients. Blood samples were obtained before and after neoadjuvant therapy from 30 patients with invasive breast cancer, and the expression of CD14 and CD16 was assessed via flow cytometry. The patients’ sCD163 levels were also determined in both the serum and culture supernatant using enzyme-linked immunosorbent assay (ELISA). The results revealed that NACT was associated with a significant decrease in double-positive monocytes and sCD163 levels. In addition, both double-positive monocytes and serum sCD163 were significantly associated with a partial clinical response. Double-positive monocytes and serum sCD163 levels may be related to therapeutic response, suggesting their possible predictive value in breast cancer patients receiving NACT.

Outcomes after medical treatment for primary aldosteronism: an international consensus and analysis of treatment response in an international cohort.

Outcomes after medical treatment for primary aldosteronism: an international consensus and analysis of treatment response in an international cohort.

Neoadjuvant chemotherapy with FOLFOXIRI for high-risk relapsed locally advanced colon cancer: A single-arm phase II trial.

201 Background: To evaluate the safety and efficacy of neoadjuvant chemotherapy (NAC) with three drug-intensity chemotherapy (oxaliplatin, irinotecan, and fluorouracil [FOLFOXIRI]) in patients with high-risk factors for recurrence and metastasis of locally advanced colon cancer (hr-LACC). Methods: A single-arm, open-label, phase II trial was conducted at West China Hospital of Sichuan University from July 2020 to Oct 2023. Patients with T4a/b or (and) N2/fused lymph nodes) and no distant metastases were considered as the hr-LACC patients. Eligible enrolled patients received four cycles of NAC with FOLFOXIRI followed by surgery and adjuvant chemotherapy with capecitabine and oxaliplatin (CAPOX) for two to five cycles or single-agent capecitabine for five cycles or observation. The primary endpoint was the rate of TRG grade 0-2 according to the criteria of NCCN guideline. Results: Of 72 patients enrolled (median age 53 [18-74] years,65 were T4a/b [90.2%], 66 were N2 [91.6%]), 58 patients (80.6%) completed four cycles of FOLFOXIRI. Three patients (4.2%) achieved clinical complete response. Twenty-eight patients (39.4%) obtained clinical partial response. The most common adverse event (AE) was nausea (86.1%, 62/72); grade 3-4 AEs occurred in 37 of 72 patients (51.4%).R0 resection was achieved in 64 of 64 patients, and the TRG (0-2) rate was 87.5% (56/64). The pathologic complete response rate was 7.8% (5/64). The proportions of pT0-2 and pN0 were 21.9% and 68.8%, respectively. Only three (4.7%) patients had prolonged hospital stay due to perioperative complications. No patient died within 30 days and 90 days after surgery. The 2-year tumor recurrence rate was 17.2%. Conclusions: For patients with hr-LACC, NAC with FOLFOXIRI regimen was safe and effective. Longer follow-up and larger clinical studies are needed to validate this innovative regimen. Clinical trial information: NCT05018182 .

95. Novel Antifungal Olorofim Use in Intractable CNS and Non-CNS Disseminated Coccidioidomycosis

Abstract Background Disseminated coccidioidomycosis (DCM) requires long courses of antifungal treatment. Olorofim, a novel antifungal in development, selectively blocks pyrimidine biosynthesis by inhibiting fungal dihydroorotate dehydrogenase (DHODH), and we evaluated its impact on clinical and mycologic response in patients with refractory DCM. Methods Adults >18y with limited or no treatment options enrolled in NCT03583164 (Study 32), an open label olorofim Phase 2b study. A Main Phase of 84+6 days was followed by an Extension Phase; we report here outcomes through 1 year. Results 41 DCM patients enrolled at 10 US sites from 05/2019 to 08/2022. Median age was 47y (range 21-72y). 30 (73.2%) had CNS disease, of whom 13 (43%) had ventriculoperitoneal shunt or Ommaya reservoir. Median time from DCM diagnosis to olorofim initiation was 936d (range 47d to 8y). Median (mean) olorofim treatment was 353d (382d). Data Review Committee (DRC)-adjudicated EORTC-MSG was Partial Clinical Response (PCR) in 28 (68.3%) at Day 42 and 27 (65.9%) at Day 84. Complete Clinical Response (CCR) was in 3 (7.3%) at both timepoints. Constitutional findings (fever, malaise) often resolved within 4 weeks. Integrated Overall Response (Clinical + Mycologic + Imaging) was 0% at Day 42 & 84 due to slow resolution of serologic findings of DCM, even in patients with CCR. Patients in the Extension Phase had PCR or CCR ranging 52.6% to 65.8% with lower rates due, in part, to missing data at study visit dates being assessed as failures, in addition to the fluctuating clinical status of DCM patients over time. Hepatic injury, judged at least possibly related to olorofim was 9 (22.0%) in Main Phase, was managed by dose reduction/pause, and led to discontinuation in 1 (2.4%) patient. Non-serious and self-limited GI symptoms were noted in 16 patients (39%) of which 1 (2.4%) was related to olorofim. Three deaths during Extension Phase were not attributed to olorofim. Conclusion Olorofim has a positive benefit-risk profile in DCM patients with no or limited treatment options. Favorable Clinical Responses were seen in 73.2% and often sustained through 1 year of treatment. Hepatic injury was usually manageable with monitoring. Future studies should assess earlier use of olorofim in serious DCM. Disclosures Fariba Donovan, MD/PhD, F2G: Grant/Research Support George R. Thompson, III, MD, Astellas: Advisor/Consultant|Cidara: Advisor/Consultant|Cidara: Grant/Research Support|F2G: Advisor/Consultant|F2G: Grant/Research Support|Melinta: Advisor/Consultant|Melinta: Grant/Research Support|Mundipharma: Advisor/Consultant|Mundipharma: Grant/Research Support|Pfizer: Advisor/Consultant Thomas F. Patterson, MD, F2G: Grant/Research Support Martin Hoenigl, MD, Aicuris: Advisor/Consultant|Astra Zeneca: Honoraria|Gilead: Grant/Research Support|Gilead: Honoraria|IMMY: Grant/Research Support|Melinta: Grant/Research Support|Melinta: Honoraria|MSD: Grant/Research Support|Mundipharma: Grant/Research Support|Mundipharma: Honoraria|Pfizer: Grant/Research Support|Pulmocide: Advisor/Consultant|Pulmocide: Grant/Research Support|Scynexis: Advisor/Consultant|Scynexis: Grant/Research Support|Shionogi: Honoraria Joanna M. Schaenman, MD, PhD, FAST, Eurofins Viracor: Honoraria|F2G: Grant/Research Support|MedCure: Advisor/Consultant|Moderna: Clinical trial support to institution|OneLegacy: Advisor/Consultant Shmuel Shoham, MD, F2G: Grant/Research Support Monica K. Sikka, MD, F2G: Grant/Research Support Andrej Spec, MD, MSCI, F2G: Grant/Research Support Mark Bresnik, MD, F2G Ltd: Employee John H. Rex, MD, F2G: Employee

P-1053. Invasive Fusariosis: 5-Year Update from a Single-Center Experience in the Voriconazole Era

Abstract Background Invasive fusariosis is a rare but aggressive infection seen in immunocompromised patients that is often multidrug resistant. The optimal therapeutic approach in the presence of elevated MICs to standard antifungal treatment remains unknown and careful monitoring of local epidemiology of this infection is needed. We performed a retrospective review of invasive fusarium infections to help guide management at our center. Methods We identified all cases of invasive Fusarium infection between January 2019 and April 2024. We collected patient characteristics, including clinical presentation, therapy, and 12-week outcomes, as well as organism speciation and susceptibility testing. Results Seven patients were diagnosed with either proven (6, 86%) or probable (1, 14%) invasive fusariosis. The median age was 60 years and six (86%) patients were male. Four (57%) had hematologic malignancies, of which 3 (75%) received stem cell transplant, 1 (14%) idiopathic neutropenia, 1 (14%) severe burns, and 1 (14%) received solid organ transplant. Four (57%) had prolonged preceding neutropenia. Cutaneous lesions were the most common presentation (5, 71%). The four cases in neutropenic hosts had cutaneous lesions with presumed or confirmed disseminated disease involving the sinuses or lung. Three (43%) received combination therapy with voriconazole and terbinafine, 2 (29%) received posaconazole, 1 (14%) received amphotericin, and 1 (14%) received voriconazole. Fusarium solani complex was the most commonly isolated species (2, 29%). Species identification was not available in 3 cases. Susceptibility testing was available in 5 (71%) cases and MICs to voriconazole were ≥16 µg/mL and to terbinafine were ≥2. All 4 cases treated with voriconazole had elevated MICs and yet exhibited a partial (2, 50%) or complete clinical response (2, 50%) to treatment. 12-week survival was seen in 4 (57%) of cases, with one patient lost to follow-up. Conclusion Mortality to invasive fusariosis is high but remains similar at our center compared to the 2002-2014 period. Diagnosis remains challenging and tissue biopsy is critical. Despite elevated MICs, clinical responses to voriconazole with or without the addition of terbinafine are observed. Disclosures All Authors: No reported disclosures

P0792 Remission rates in Complex Perianal Fistulizing Crohn's Disease – Real-life experience of a tertiary reference center

Abstract Background The treatment of complex perianal fistula (cPF) in Crohn’s Disease (CD) requires an integrated and multidisciplinary approach (1) This phenotype affects up to a third of CD patients (2,3) and significantly harms their quality of life (4). This study aims to review the experience of a tertiary reference center and identify prognostic factors related to non-response to treatment. Methods Adult patients with CD who underwent surgery for cPF, in a tertiary reference center, between 2015 and 2023 were retrospectively reviewed. Extracted data included baseline demographic data, clinical recurrence of perianal disease, and resolution of perianal disease. Cases were stratified according to clinical response to treatment of perianal disease after surgery: complete clinical response (clinical remission), partial clinical response, clinical nonresponse or clinical recurrence. Results Seventy-nine patients (50.6% male) were included; the average age was 28 years (Q1=21 and Q3=38). Median follow-up of 85 months (interquartile range, 37-124); the multidisciplinary team discussed all of them. At the time of first surgery, 53.2% of patients had trans-sphincteric cPF, 22.8% had supra-sphincteric cPF, and 15.2% had rectovaginal cPF. In 88.6% of patients, the first procedure was seton placement. All but two patients were treated with 1 to 4 biologic drugs. The two patients treated with mesenchymal stem cells transplantation achieved a complete clinical response at 24 weeks, maintained at 52 weeks of follow-up. Female sex was a protective factor for nonresponse to treatment, and supra-esfincteric fistula was factor associated with the risk of nonresponse or recurrence. At end of follow-up, 78.5% of patients had a complete or partial response, and 21.5% had a nonresponse or a recurrence. Due to perineal destruction 3 patients required an ostomy, and the other 3 a proctectomy. Conclusion This real-life study showed that a multidisciplinary approach, including surgical intervention, can completely heal Crohn's disease perianal fistula in more than seventy-eight percent of patients. Supra-esphincteric fistula was a risk factor for worse disease outcomes, and female sex was a protective factor for nonresponse.

Safety and clinical efficacy of neoadjuvant chemoradiation therapy with immunotherapy for organ preservation in ultra-low rectal cancer: preliminary results of the CHOICE-I trial: a prospective cohort study.

To explore the safety and efficacy of neoadjuvant chemoradiotherapy (nCRT) combined with a PD-1 antibody in improving complete clinical response (cCR) and organ preservation in patients with ultra-low rectal cancer. This was a prospective phase II, single-arm, open-label trial. Patients with confirmed pMMR status T 1-3a N 0-1 M 0 retcal adenocarcinoma were included. Long-course chemoradiotherapy was delivered to a dose of 50Gy. A PD-1 antibody was added 2weeks after the first radiotherapy session, and two courses were administered. After chemoradiotherapy, CapeOX plus PD-1 antibody was administered to patients for two cycles. After evaluation, patients with cCR were managed with a watch-and-wait (W&W) approach. Local excision or a W&W approach was performed for patients with near complete clinical response (ncCR) as per multidisciplinary team decision. Radical surgery was recommended for poorly regressed or progressed tumors. Twenty-five patients were enrolled, but two patients withdrew from the study. A total of 23 patients completed the entire neoadjuvant therapy. Ten and five patients achieved cCR and ncCR, respectively, and the rest had a partial clinical response. Patients with cCR were managed with W&W. Four patients with ncCR underwent local excision and were managed using W&W. Eight patients with partial clinical response underwent anus-preserving surgery. At the last follow-up, the rectum and anus preservation rates were 63.4% (14/22) and 95.5% (21/22), respectively. nCRT combined with immunotherapy tended to achieve better cCR and rectum preservation rates with good tolerance in patients.

Personalized Medicine in Histiocytic Disorders: Novel Targets in Patients Without MAPK Alterations.

BRAF and MEK inhibitors are standard treatments in histiocytic disorders, such as Erdheim-Chester disease (ECD). Some patients lack MAPK-pathway alterations, making these treatments less effective. We describe three patients with histiocytic disorders who have novel non-MAPK pathway alterations. These alterations were studied through genomic and in silico analyses when applicable, then treated with off-label medications rationally selected on the basis of genomic alterations. Patient 1 had rapidly progressive ECD involving the CNS. A CSF1R in-frame deletion (p.S560_P566del) was identified, and in silico modeling predicted a gain-of-function mutation. This alteration was targeted with pexidartinib, which led to a clinical complete response (CR) within 2 months, and a partial response (PR) on imaging after 3 months. After 15 months, the disease became resistant to pexidartinib and transformed to histiocytic sarcoma. Patient 2 has skin-only involvement of a xanthogranuloma disorder. A KIF5B-FGFR1 fusion was identified on RNA sequencing and targeted with pemigatinib. At 24 months of follow-up, she remains in a clinical PR. Patient 3 has ECD involving the bone marrow, gastrointestinal tract, and subcutaneous tissues. A MEF2C-FLT3 fusion was identified and targeted with sorafenib. He achieved a clinical CR and radiographic PR within 3 months, which has continued for 30 months. We report three patients with histiocytic disorders harboring novel alterations who had sustained responses to off-label kinase inhibitors specific to their histiocytic disorder. Pathogenic variants outside of the MAPK pathway, including variants of unknown significant, may be targeted with readily available small molecules.

Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer: Insights from the Western Australian Context.

Recent studies have associated total neoadjuvant therapy (TNT) with better treatment adherence, decreased toxicity, improved complete clinical response and anal sphincter preservation rates in patients with locally advanced rectal cancer (LARC). However, real-world experience with TNT in the management of LARC remains limited. This study aimed to evaluate the efficacy and safety outcomes of TNT for LARC in Western Australia. Patients with LARC (cT2-4 and/or cN1-2) who underwent induction chemotherapy followed by neoadjuvant chemoradiotherapy or neoadjuvant chemoradiotherapy followed by consolidation chemotherapy, followed by surgery were recruited from two hospitals in Western Australia. Efficacy outcomes assessed included clinical response (complete, partial, no response), and pathologic complete response (pCR) rate, R0 resection rate, and R1 resection rate were evaluated. Those patients who achieved clinical complete response following TNT were given the option of active surveillance. The safety and tolerability of TNT were assessed. 32 patients with LARC were treated with TNT. In total, 17 patients (53%) received chemoradiotherapy followed by consolidation chemotherapy and 15 patients (47%) received induction chemotherapy followed by chemoradiotherapy. Nine (28%) of the patients with LARC treated with TNT had a complete clinical response, twenty-one (66%) patients had a partial clinical response, and two (6%) patients had no response to TNT. Of the 32 patients, 27 (84%) underwent surgery. There was a 100% R0 resection rate. The pCR rate was 15%. pCR, clinical response, and the R0 resection rate were similar between the two TNT regimens. TNT was well tolerated, with the majority of patients (88%) completing the chemotherapy course with grade 1 and 2 adverse effects. In conclusion, TNT emerges as a promising approach for the management of LARC. However, further research is warranted to refine the optimal TNT protocols, determine its long-term outcomes, and identify patient populations who would benefit the most from this innovative therapeutic strategy.

7787 Primary Aldosteronism Medical Treatment Outcomes (PAMO): An International Consensus on Outcome Assessment Criteria and Multicentre Study

Abstract Disclosure: J. Yang: None. J. Burrello: None. J. Goi: None. T.A. Williams: None. W.F. Young: Consulting Fee; Self; Arena Pharmaceuticals, Inc.. Other; Self; Crinetics Pharmaceuticals. P.J. Fuller: None. P. Investigators: None. Primary aldosteronism (PA) is the most common endocrine cause of hypertension. Mineralocorticoid receptor antagonists, at adequate doses, lower blood pressure and cardiovascular risk in patients with PA. However, there is a lack of a standardized approach to medical therapy and subsequent outcomes assessment. We aimed to: 1) establish criteria for assessing outcomes of targeted medical treatment of PA, and 2) evaluate outcomes using these criteria across an international cohort. A panel of 31 PA experts from 31 centres across four continents used the Delphi method, including three rounds of online questionnaires, to reach consensus. Clinical data were then collected from consecutive patients with PA who started targeted medical treatment between 2016 and 2021 at the participating centres. Consensus was reached for six outcomes, including complete, partial, or absent biochemical response, and complete, partial, or absent clinical response. “Complete biochemical response” was defined as “correction of hypokalemia without potassium supplementation, and normalization of plasma renin activity or concentration”; while “absent biochemical response” was defined as “persistent hypokalemia and/or persistently suppressed or low plasma renin activity or concentration without change from baseline”. “Complete clinical response” was defined as “normal blood pressure without additional antihypertensive medications”; while “absent clinical response” was defined as “the same or increased blood pressure compared to before targeted treatment with same or more antihypertensive medications, not counting targeted therapy”. Of 1483 patients (mean age 52y, 48% female) from 28 centers, 232 (16%) had a complete clinical response, and 719 (49%) had a complete biochemical response at the most recent follow-up (median 29 months after treatment initiation). Compared to those with partial or absent clinical response, patients with complete clinical response had a significantly higher proportion of women and lower proportion with diabetes, stroke or left ventricular hypertrophy. They also had a significantly shorter duration of hypertension, lower BMI, higher eGFR and lower defined daily dose of antihypertensives at baseline. In contrast, these differences were not observed in those with a complete, partial or absent biochemical response. The defined daily dose of targeted therapy did not differ across the various response categories. In conclusion, we have established an international expert consensus for standardized criteria to evaluate the response to targeted medical treatment of PA, facilitate comparisons of outcome data and guide clinicians who manage PA. In a retrospective international cohort, less than half of medically-treated patients reached the established biochemical treatment targets. Further work is needed to increase the rate of complete response. Presentation: 6/3/2024

Assessment of Radiotherapy as a Standalone Treatment Following Neoadjuvant Chemotherapy in Nonmetastatic Breast Cancer: A SEER Database Analysis.

Traditional breast cancer management involves surgery followed by systemic therapies. However, advancements in neoadjuvant chemotherapy (NACT) raise questions about the necessity of surgery in cases with an excellent response to NACT. This study investigates the outcomes of radiotherapy without surgery in selected patients with nonmetastatic breast cancer after a complete or substantial response to NACT. A retrospective study was conducted using the SEER database, reviewing records from 2010 to 2020 for patients with nonmetastatic breast cancer who received NACT, associated with a clinical response, followed by radiotherapy alone. The population included 123 patients, stratified into complete clinical response (cCR) and non-cCR (partial or unspecified clinical response) cohorts. Overall survival (OS) and cancer-specific survival (CSS) were analyzed using Kaplan-Meier and Cox proportional hazards models. The median follow-up was 41 months. Among the patients, 17 (13.82%) achieved cCR. The 5-year OS and CSS for the entire cohort were 65.8% and 71%, respectively, with the cCR group achieving 100% rates for both. Age above 60 and larger tumor size (T3 to T4) were associated with lower OS. The non-cCR group showed a 5-year OS of 61.5% and CSS of 67.1%. This study indicates that omitting surgery in patients with a cCR to NACT may be feasible, as evidenced by this subgroup's 100% OS and CSS rates at 5 and 10 years. These promising results support further research into less invasive breast cancer management. However, prospective studies must validate these findings and identify suitable patients for nonsurgical approaches.

Efficacy of Methotrexate and Anti-TNF Combination Therapy in Adults with Refractory Crohn's Disease.

Biological medications have played a significant role in maintenance therapy for Crohn's disease (CD), but some cases become refractory to these agents. Methotrexate (MTX) appears to be a cost-effective and readily available drug for enhancing the effectiveness of maintenance therapy when used in combination with anti-tumor necrosis factor (anti-TNF) therapy in such cases. However, its effectiveness is still to be established. We aimed to assess the efficacy of MTX and anti-TNF combination therapy in patients with refractory CD. A retrospective cohort study was conducted on adult patients with CD who were refractory to anti-TNF therapy and were initiated on weekly intravenous MTX in addition to the anti-TNF therapy. These patients were then followed up for over a year. The primary outcome measured was the clinical response to treatment, based on the Harvey-Bradshaw Index. The secondary outcomes included assessing the adverse events and complications of MTX therapy. Of 70 patients, 44 were included in the final analysis. Among them, 30 patients (68.2%) achieved complete remission, four patients (9.1%) had a partial clinical response, and 10 patients (22.7%) required surgery. The adverse events and complications of MTX therapy were mild and infrequent (9.1%). None of the demographic or clinical factors were significantly associated with response to treatment (P>0.05). Combining MTX with anti-TNF therapy appears to be an effective and safe treatment for patients with Crohn's disease, particularly those with severe disease who are less responsive to monotherapy. However, further studies are needed to confirm these findings.

Hypophosphatemic Rickets as a Key Sign for the Diagnosis of Hereditary Tyrosinemia Type 1: Case Reports and Narrative Review of the Literature.

Hereditary tyrosinemia type 1 (HT-1) is an inborn error of metabolism caused by a defect in tyrosine (tyr) degradation. This defect results in the accumulation of succinylacetone (SA), causing liver failure with a high risk of hepatocarcinoma and kidney injury, leading in turn to Fanconi syndrome with urine loss of phosphate and secondary hypophosphatemic rickets (HR). HT-1 diagnosis is usually made in infants with acute or chronic liver failure or by neonatal screening programs. HR is rarely described in the literature as the main feature or chief complaint of patients with HT-1. Clinical cases: We present three children who presented signs of HR during infancy. Patient 1 had early liver dysfunction, leading to a quick diagnosis of HT-1. Patients 2 and 3 started conventional therapy for HR (calcitriol and oral phosphate) with partial clinical response. Later, both developed liver dysfunction, and patient 3 presented neurological symptoms (porphyria-like crises). An HT-1 diagnosis was made using tandem mass spectrometry, which confirmed high plasma levels of SA and tyr. After diagnosis, all started treatment with a specific diet and nitisinone with prompt recovery and a quick remission of clinical signs of HR, being able to discontinue their conventional rickets therapy successfully. Conclusion: We present three patients with HT-1 whose main complaint was HR. It is important to know the main features of this metabolic disorder and have a high index of suspicion when we follow-up children with HR, especially if they are not responding to conventional therapy or develop liver dysfunction.

A study of the assessment of pathological response to neoadjuvant chemotherapy in patients with breast cancer

Abstract: BACKGROUND: Neoadjuvant chemotherapy therapy ( NACT) has emerged as an integrated therapeutic approach to treat locally advanced breast cancer in order to down stage the tumour and to assess tumour response to chemotherapy. The aims of this study were to estimate the incidence of complete and partial pathological response in patients undergoing NACT for breast cancer and to evaluate the clinico pathological parameters associated with pathological response. MATERIALS AND METHODS: The study included breast cancer specimens from patients who had received NACT. The pathological response to NACT was assessed by the AJCC protocol and the morphological features associated with NACT were recorded. The clinicopathological parameters associated with complete pathological response were also studied. The association between the clinicopathological paramaters and pathological response was studies using Chi square and Fisher exact tests. RESULTS: There were a total of 50 women who underwent surgery for breast cancer following NACT. The mean age was 56.5 years. The majority (59.1%) belonged to stage IIIB followed by Stage III A ( 30.6%). 73.4% of cases showed clinical partial response, 14.2 % showed no response and 12.2 percent showed Pathological Complete Response (pCR). ER and PR negative and Her 2 positive status were the parameters significantly associated with pCR. CONCLUSIONS: Pathological evaluation is the most reliable method to assess response to NACT in breast cancer patients which may further influence management decisions. This study showed a much lower frequency of pCR when compared to other Indian studies. It is recommended that all patients who are treated with NACT undergo prior core needle biopsy with hormone receptor and Her 2 testing as they may have a bearing on pCR.

The Efficacy and Safety of Endoscopic Balloon Dilatation in the Treatment of Functional Post-Sleeve-Gastrectomy Stenosis

Background and Objectives: Functional gastric stenosis, a consequence of sleeve gastrectomy, is defined as a rotation of the gastric tube along its longitudinal axis. It is brought on by gastric twisting without the anatomical constriction of the gastric lumen. During endoscopic examination, the staple line is deviated with a clockwise rotation, and the stenosis requires additional endoscopic manipulations for its transposition. Upper gastrointestinal series show the gastric twist with an upstream dilatation of the gastric tube in some patients. Data on its management have remained scarce. The objective was to assess the efficacy and safety of endoscopic balloon dilatation in the management of functional post-sleeve gastrectomy stenosis. Patients and Methods: Twenty-two patients with functional post-primary-sleeve-gastrectomy stenosis who had an endoscopic balloon dilatation between 2017 and 2023 were included in this retrospective study. Patients with alternative treatment plans and those undergoing endoscopic dilatation for other forms of gastric stenosis were excluded. The clinical outcomes were used to evaluate the efficacy and safety of balloon dilatation in the management of functional gastric stenosis. Results: A total of 45 dilatations were performed with a 30 mm balloon in 22 patients (100%), a 35 mm balloon in 18 patients (81.82%), and a 40 mm balloon in 5 patients (22.73%). The patients’ clinical responses after the first balloon dilatation were a complete clinical response (4 patients, 18.18%), a partial clinical response (12 patients, 54.55%), and a non-response (6 patients, 27.27%). Nineteen patients (86.36%) had achieved clinical success at six months. Three patients (13.64%) who remained symptomatic even after achieving the maximal balloon dilation of 40 mm were considered failure of endoscopic dilatation, and they were referred for surgical intervention. No significant adverse events were found during or following the balloon dilatation. Conclusions: Endoscopic balloon dilatation is an effective and safe minimally invasive procedure in the management of functional post-sleeve-gastrectomy stenosis.

Clinicopathological correlation of patients with lupus nephritis: Data from a tertiary center in Saudi Arabia.

Systemic lupus erythematosus mainly affects young women, and approximately half of systemic lupus erythematosus patients develop lupus nephritis (LN). However, data on the types and remission rates of LN in Saudi Arabia are limited. Therefore, we aimed to highlight the LN remission rates in our population. A retrospective record review was conducted between January 2007 and December 2020 in a tertiary center in the western region of Saudi Arabia to determine the remission rates among patients with biopsy-proven LN who met the EULAR\ACR 2019 classification criteria. We identified 59 patients with biopsy-proven LN, mostly in young women. The common histopathological pattern was Class IV LN in 26 patients (44%). Three induction protocols were identified, along with systemic steroids: the high-dose cyclophosphamide protocol in 21 patients (35.6%), low-dose protocol in 4 patients (6.8%), and mycophenolate mofetil (MMF) in 41 patients (69.5%). Partial response, defined as the reduction of the 24-hour proteinuria by 25% at 3 months and 50% at 6 months, was achieved in 18 patients (33.3%) at 3 months and decreased to 13 patients (24.1%) at 6 months. Complete clinical response, defined as 24-hour urinary protein between 500 and 700 mg at 12 months, was achieved in 44 patients (81.5%). Complete remission was higher among patients with Class IV LN (64.4%). The achievement of partial clinical response at 3 months was significantly lower among patients with hypertension (P = .041). This study presented the LN remission rates in a single center in Saudi Arabia. Similar to previous studies, Class IV LN were the most common histopathological finding in this study. Complete remission at 12 months was achieved in 44 (81%) patients. Delayed remission is associated with hypertension at the time of LN diagnosis.

The Efficacy of Trigger Site Surgery in the Elimination of Chronic Migraine Headache: An Update in the Rate of Success and Failure.

Migraine headache (MH) is a prevalent neurovascular disorder that affects approximately 15% of the global population. They are more common in women and typically affect young and middle-aged individuals. Chronic MH is characterized by headaches occurring on ≥15 days per month for over three months. While only 5% of MHs are refractory, about 20%-50% do not respond to pharmacologic treatments. As a result, surgical interventions have emerged as an alternative method to eliminate MH since 2000 AD. These surgical treatments primarily target the peripheral mechanisms of MH, focusing on common trigger sites. Migraine surgery involves neurolysis of sensory branches of trigeminal and occipital nerves that supply the face and back of the head. Numerous clinical studies conducted between 2000 and 2021 have extensively described surgical interventions and their prognostic outcomes. After surgery, up to 80% of patients reported complete elimination of headaches, while 20%-35% experienced no relief. The failure to achieve complete elimination of MH can be attributed to various factors. The most common reason for a partial clinical response is the failure to identify all trigger sites or inadequate surgery on the trigger sites. In this review, we aim to provide an overview of current surgical interventions for MH at different trigger sites, including recent updates, success and failure rates, and potential causes of failure.

Long Term Outcomes in Idiopathic Inflammatory Myositis: An Observational Epidemiologic Study over 15 Years.

We report a longitudinal observational cohort of idiopathic inflammatory myositis (IIM) focusing on the long-term clinical outcome and associated parameters. IIM patients were classified as per Bohan and Peter criteria. In those with ≥ 24 months of follow-up; the treatment response, functional outcomes, and damage at last follow-up were recorded. Complete clinical response and clinical remission as defined by Oddis et al., was used to define outcomes at last follow-up. The cohort consists of 175 patients, mean age 40.9 (+12.6) years, M:F 1:3.3; and the major subsets were dermatomyositis (44.6%), overlap myositis (25.7%), antisynthetase syndrome (6.3%), polymyositis (14.3%), and juvenile DM/OM (8.6%). Ninety-four patients have followed up for 24 months or more, with the median (IQR) of 65(35,100.7) months. Of them, 74.1% and 11.8% had complete and partial clinical responses respectively at the last follow-up. In our cohort 40.2% were off-steroids and 13.8% were in clinical remission at the last follow-up. Complete clinical response was associated with better functional outcomes and lesser damage as determined by HAQ-DI of 0[OR10.9; 95%CI (3.3,160)], MRS [OR 3.2; 95%CI (1.4,7.3)] and lesser MDI [OR 1.7; 95% CI (1.1,2.7)] respectively as compared to partial response (unadjusted analysis). Baseline parameters and IIM subsets did not significantly influence the functional outcome and damage. The mortality rate in our cohort is 24/175 (13.7%), the disease-specific mortality rate being 9.1%. Large majority of deaths were early, associated with active disease. We report good long-term outcomes in all major myositis subsets. Partial clinical response to treatment is associated with worse functional outcomes and damage accrual. Death occurs early in association with active disease.

Lateral Pelvic Nodal Management and Patterns of Failure in Patients Receiving Short-Course Radiation for Locally Advanced Rectal Cancer.

Management of lateral pelvic lymph nodes in locally advanced rectal cancer is controversial, with limited data indicating the optimal approach. Additionally, no data exists regarding treatment of lateral nodes in the setting of short course radiation and nonoperative intent. We evaluate a novel approach incorporating simultaneous integrated boost to suspicious lateral nodes. This was a retrospective study. This study was conducted at a large, tertiary referral center. Patients treated with radiation and consolidation chemotherapy were included. All primary tumors were biopsy confirmed and disease-staged with pelvic magnetic resonance imaging. Primary tumors were biopsy proven and staged with pelvic magnetic resonance imaging. A subset of lateral pelvic lymph nodes patients received simultaneous integrated boost to 35 Gy in 5 fractions. Then, chemotherapy was administered with the majority receiving mFOLFOX (modified folinic acid, fluorouracil, and oxaliplatin). Clinical partial response required total mesorectal excision. Patterns of failure and survival analyses by subgroup were assessed. Outcomes based on receipt of radiation were compared across node status. Between January 2017 - January 2022, 155 patients were treated with short course and chemotherapy with 121 included in final analysis. Forty-nine percent underwent nonoperative management. Median follow-up was 36 months and median age was 58 years. Thirty-eight patients (26%) had positive lateral pelvic lymph nodes. Comparing lateral node status, progression-free survival was significantly worse for patients with positive disease (p < 0.001) with a trend for worse overall survival. Receipt of nodal boost in patients with lateral nodes resulted in meaningful locoregional control. Nodal boost did not contribute to additional acute or late GI toxicity. Limitations included retrospective nature and lack of lateral nodes pathology; however, thorough radiographic review was performed. Lateral node positive rectal cancer is correlated with worse oncologic outcomes and higher locoregional failure. Boost to clinically positive lateral nodes is a safe approach in the setting of short course and in those receiving nonoperative intent.