Significant Clinical Improvement Research Articles

Microbiome Modulation in Acne Patients and Clinical Correlations

Background: The imbalance of skin microbiota in acne can induce changes leading to induction or to aggravation of chronic inflammatory lesions; complex mechanisms are involved. Cutibacterium acnes (C. acnes) ribotypes RT4 and RT5 express more biofilm and are associated with inflammatory acne lesions. C. acnes RT6 is a non-acne ribotype, beneficial for the skin. Objectives: In an open clinical trial, acne adults were included and assessed clinically at baseline and at month 2 using the Investigator Global Assessment of Acne (IGA) score. A topical emulsion was applied twice daily for 2 months (M2) in each included patient. In the same series of acne patients, skin swab samples were collected from acne patients at baseline and M2 from lesional and non-lesional skin; skin swabs were collected for the metagenomic long-read analysis of microbiota. Materials and Methods: Acne patients with a gravity score IGA of >1<3 were included in this pilot study. An emulsion of O/W formulated with vegetal extract of Umbelliferae associated with a polysaccharide at 1% was applied twice daily for 2 months. At baseline and M2 clinical assessments were made; skin swab samples were also taken for microbiota analysis from lesional and non-lesional skin in each included patient. Extractions of genomic DNA (gDNA) from swab samples from baseline and from M2 were made, followed by full-length (V1–V9) amplification of the 16S rDNA and sequencing of amplicon libraries for strain-level bacterial community profiling. Results: In a series of 32 adult acne patients, the mean initial IGA scale was 3.1; at M2 the IGA scale was 1.5 (p < 0.001). The mean decrease in acne lesions was by 63%. Microbiome metagenomic long-read analysis in these series was mainly dominated by C. acnes followed by Staphylococcus epidermidis (S. epidermidis). The density of C. acnes ribotypes RT6 (non-acne strain) was increased at M2 compared to baseline and the density of ribotypes C. acnes RT1 to RT5 was decreased at M2, compared to baseline (p < 0.0001). S. epidermidis ribotypes (1 to 36) were non significantly increased at M2, compared to baseline (p < 0.1). Conclusions: In a series of 32 acne patients that applied an emulsion based on vegetal extract of Umbelliferae and a polysaccharide at 1% twice daily, a significant clinical improvement in IGA scale for acne lesions was seen at M2, compared to baseline (p < 0.0001). The clinical improvement was correlated with an improvement in skin microbiome at M2 compared to baseline, indicated by the increase in the relative abundance of non-acne strain of C. acnes ribotype 6 and of the decrease in the relative abundance of acne strains ribotypes C. acnes RT1 to RT5.

Anatomical outcomes and complications of sacrocolpopexy using Surelift Uplift mesh: A multicentric observational study.

The study evaluated the anatomical and functional outcomes, as well as the safety data of laparoscopic sacrocolpopexy (LSC) for pelvic organ prolapse (POP) using a lightweight macroporous mesh. A multicentric observational study was developed including five expert centers between March 2011 and December 2019. Inclusion criteria were female patients with symptomatic ≥stage II POP (POP-Q classification), who underwent a LSC. A lightweight and macroporous mesh device (Surelift Uplift) was used. Baseline anatomical positions were evaluated using POP-Q stage. The anatomical outcomes and procedural complications were assessed during the postoperative period. Primary outcomes were anatomical success, defined as POP-Q stage ≤I, and subjective success, defined as no bothersome bulge symptoms, and no repeat surgery or pessary use for recurrent prolapse. A total of 325 LSCs were analyzed with a median patient age of 66 (interquartile range [IQR] 61-73). After a median follow-up of 68 months (IQR 46.5-89), anatomical success was found in 88.9%, whereas subjective success was seen in 98.5% of the patients. Recurrent prolapse presented as cystocele (1.5%). Reported complications were bladder (4.6%) or rectum lesions (0.6%), de novo urinary incontinence (12.9%), and mesh extrusion (1.2%). LSC provides significant clinical improvement and excellent anatomical results, with a low risk of serious complications for women with ≥2 grade POP in a real clinical practice setting.

A case of pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension - a happily completed odyssey

Chronic thromboembolic pulmonary hypertension is a rare condition that is usually a consequence of prior acute pulmonary embolism. It is caused by persistent obstruction of pulmonary arteries by organized thrombi resulting in redistribution of blood flow and secondary pulmonary microvascular remodelling. Thus, pulmonary vascular resistance and pulmonary artery pressure are increased leading to right ventricle pressure overload, development of right heart failure and death. In eligible patients pulmonary endarterectomy is the standard of care and it can result in complete normalization of haemodynamics and right ventricular morphology and function. We present the case of a patient with chronic thromboembolic pulmonary hypertension with severe right ventricular dilation and dysfunction and refractory heart failure. After successful pulmonary endarterectomy we observed almost complete normalization of hemodynamics and restoration of right ventricular dimensions and function, as well as significant clinical improvement.

Trastuzumab deruxtecan in HER2-positive advanced gastric cancer: exploratory biomarker analysis of the randomized, phase 2 DESTINY-Gastric01 trial.

Trastuzumab deruxtecan (T-DXd) showed statistically significant clinical improvement in patients with human epidermal growth factor receptor 2-positive (HER2+) gastric cancer in the DESTINY-Gastric01 trial. Exploratory results from DESTINY-Gastric01 suggested a potential benefit in patients with HER2-low gastric cancer. Spatial and temporal heterogeneity in HER2 expression or gene alteration, an inherent characteristic of gastric cancer tumors, presents a challenge in identifying patients who may respond to T-DXd. Specific biomarkers related to therapeutic response have not been explored extensively. Exploratory analyses were conducted to assess baseline HER2-associated biomarkers in circulating tumor DNA and tissue samples, and to investigate mechanisms of resistance to T-DXd. Baseline HER2-associated biomarkers were correlated with objective response rate (ORR) in the primary cohort of patients with HER2+ gastric cancer. The primary cohort had 64% concordance between HER2 positivity and HER2 (ERBB2) plasma gene amplification. Other key driver gene amplifications, specifically MET, EGFR and FGFR2, in circulating tumor DNA were associated with numerically lower ORR. Among 12 patients with HER2 gain-of-function mutations, ORR was 58.3% (7 of 12). ORR was consistent regardless of timing of immunohistochemistry sample collection. Further investigations are required in larger studies.

Blood Viscosity and its Clinical Implications in Ischemic Stroke and Chronic Heart Failure: Insights from a Case Report

Background Blood viscosity has received increased attention as a potential predictor of ischemic stroke risk, particularly in patients with chronic heart failure (CHF). Despite the importance of this link, there has been a notable paucity of comprehensive research on the subject. Hence, the major goal of this study was to shed light on the potential importance of blood viscosity in individuals with ischemic stroke and CHF. Case Presentation An 85-year-old male was presented to the emergency department after three days of gradually decreasing consciousness. His medical history included hypertension and CHF. His Glasgow Coma Scale (GCS) was determined to be E2M5V3, and he displayed evidence of upper motor neuron facial palsy as well as right hemiparesis. The clinical assessment scores, which included the NIHSS and mRS, were 10 and 4, respectively. MRI imaging confirmed the existence of several acute infarctions. Other diagnostic procedures, including an x-ray, revealed cardiomegaly and echocardiographic findings were compatible with grade I diastolic dysfunction. His blood viscosity was 8.19 cP, which was much higher than normal. The patient was diagnosed with ischemic stroke, CHF, and hyperviscosity based on these findings. Despite a small increase in blood viscosity to 8.16 cP after a six-day treatment session, the patient showed significant clinical improvement. Unfortunately, he was readmitted immediately after being discharged and died three days later. Conclusion This case demonstrates the importance of blood viscosity in the evaluation and prognosis of patients with ischemic stroke and CHF.

Management of pediatric liver failure with therapeutic plasma exchange and continuous renal replacement therapy: A retrospective observational study.

Liver failure represents a critical medical condition, marked by the rapid decline of hepatic functions. Emerging therapies, notably therapeutic plasma exchange (TPE) and continuous venovenous hemodiafiltration (CVVHDF), have demonstrated potential in mitigating these conditions through their roles in detoxification and hepatic support. The utility of these treatments, whether applied individually or in tandem, constitutes a significant area of research concerning the management of liver failure in pediatric patients. This study aims to evaluate the role and efficacy of TPE or TPE combined with CVVHDF in the treatment of liver failure among children. This retrospective study was conducted in a LTICU by reviewing the medical history of pediatric patients aged 1 month to 18 years. Patients were admitted between January 1, 2021 and December 1, 2023 due to acute liver failure or acute-chronic liver failure. The study evaluated those who received TPE or continuous renal replacement therapy combined with TPE. In statistical analyses, a P-value of <.05 was considered statistically significant. The study involved 24 patients with liver failure, comprising 13 males and 11 females. Sixteen patients (66.6%) received only TPE, while 8 patients (33.4%) were treated with TPE and CVVHDF. For patients treated only with TPE, the median INR reduced from 3.1 to 1.26, alanine aminotransferase from 1255 to 148, and aspartate aminotransferase from 2189 to 62. Similar significant reductions were observed in the TPE and CVVHDF group: INR from 3.9 to 1.26, alanine aminotransferase from 1749 to 1148, and aspartate aminotransferase from 1489 to 62. These changes were statistically significant with P-values of .01 for each parameter in both groups. Overall, 14 patients survived without requiring a liver transplant, while 4 patients underwent liver transplantation. Our study on pediatric liver failure treatment shows that both standalone TPE and its combination with CVVHDF are effective, especially as a bridge to transplantation. With 58% transplant-free survival, these therapies demonstrate significant clinical improvements. Future multicentric studies are needed for broader validation of these findings in liver failure management.

An Observational Invasive of Explore Effect of Ayurveda Drugs in the Management of Indigestion wsr to Amajeerna and Udavarta

Due to secondary lifestyle and diet junk food may be the leading etiology for Ghrelin hypofunction. It leads to indigestion. Pioneer Ayurveda classics like Charaka Samhita, Susruta Samhita, Madhav Nidan, Astanga Hridaya etc explained aforesaid disease condition as Agnimandya, Amajeerna and Udavarta is the result of suppression of some natural urges like the desire to micturition, defecation, vomiting, hunger etc. Common symptom of Amajeerna are felling of heaviness in abdomen, nausea, belching similar just after meals. Based on classical and contemporary science a single case study was taken out in the West Bengal with an Ayurveda Interventions to rule out the clinical significant of it. In this study biochemical as well as radiological parameter were consider before and after treatment. However in this study we were found Ayurvedic treatment protocol shown a significant clinical improvement on Amajeerna and Udavarta along with patient weight reduction and management of alcoholic fatty liver may be due to drugs combined role on hepatoprotective, Ghrelin polypeptide and action on other digestive enzymes.

Cutaneous biomarkers of therapeutic efficacy in early treatment of hereditary ATTR amyloid polyneuropathy with tafamidis.

ATTR (ATTRv) amyloidosis neuropathy is characterized by progressive sensorimotor and autonomic nerve degeneration secondary to amyloid deposition caused by a misfolded transthyretin protein (TTR). Small nerve fiber neuropathy is an early clinical manifestation of this disease resulting from the dysfunction of the Aδ and C small nerve fibers. Tafamidis, a selective TTR stabilizer, has proven its efficacy in the earlier stages of hATTR. To evaluate the clinical course and utility of cutaneous pathological biomarkers in patients with ATTR amyloidosis treated with tafamidis compared to control patients. Forty patients diagnosed with early stages of ATTRv amyloidosis (polyneuropathy disability [PND] scores 0-II) underwent small and large nerve fiber neurological evaluations, and annual skin biopsies for intraepidermal nerve fiber density (IENFD) and amyloid deposition index (ADI) estimation. Thirty patients were allocated to receive tafamidis, and 10 patients served as controls. Tafamidis pharmacokinetics analysis was performed in patients who received the treatment. At baseline, 12% of patients in stage PND 0 and 28% in PND I displayed small nerve fiber denervation in the distal thigh, whereas 23% and 38%, respectively, in the distal leg. Similarly, 72% and 84% had amyloid deposition in the distal thigh and 56% and 69% in the distal leg. Following 1 year of treatment, the tafamidis group showed significant clinical improvement compared to the control group, revealed by the following mean differences (1) -9.3 versus -4 points (p = <.00) in the patient's neuropathy total symptom score 6 (NTSS-6) questionnaire, (2) -2.5 versus +2.8 points (p = <.00) in the Utah Early Neuropathy Score (UENS), and (3) +1.2°C versus -0.6 (p = .01) in cold detection thresholds. Among the patients who received tafamidis, 65% had stable or increased IENFD in their distal thigh and 27% in the distal leg. In contrast, all patients in the control group underwent denervation. The ADI either decreased or remained constant in 31% of the biopsies in the distal thigh and in 24% of the biopsies in the distal leg of the tafamidis-treated patients, whereas it rose across all the biopsies in the control group. At the 4-year follow-up, the tafamidis group continued to display less denervation in the distal thigh (mean difference [MD] of -3.0 vs. -9.3 fibers/mm) and the distal leg (mean difference [MD] -4.9 vs. -8.6 fibers/mm). ADI in tafamidis-treated patients was also lower in the distal thigh (10 vs. 30 amyloid/mm2) and the distal leg (23 vs. 40 amyloid/mm2) compared to control patients. Plasma tafamidis concentrations were higher in patients with IENFD improvement and in patients with reduced amyloid deposition. Patients without amyloid deposition in the distal leg at baseline displayed delayed disease progression at 4 years. Cutaneous IENFD and amyloid deposition assessments in the skin of the distal thigh and distal leg are valuable biomarkers for early diagnosis of ATTR amyloidosis and for measuring the progression of small nerve fiber neuropathy. Early treatment with tafamidis slows the clinical progression of the disease, skin denervation, and amyloid deposition in the skin. Higher plasma concentrations of tafamidis are associated with better disease outcomes, suggesting that increasing the drug dose could achieve better plasma concentrations and response rates. This study describes the longest small nerve fiber neuropathy therapeutic trial with tafamidis and is the first to report small fiber symptoms, function, and structural assessments as outcomes.

Percutaneous balloon mitral valvuloplasty with shockwave lithotripsy for the treatment of calcific mitral valve stenosis.

Calcific mitral stenosis (calcific MS) presents a challenge for surgical treatment and is a contraindication for most contemporary transcatheter mitral valve replacement devices (TMVR), rendering patients with very limited therapeutic options. This study aims to assess the clinical and hemodynamic follow-up after mitral valve lithotripsy (MVL). All consecutive patients who underwent MVL to treat symptomatic calcific MS at St Michael's Hospital, Toronto, Canada, were included. Patients were deemed unsuitable for mitral surgery or TMVR after heart team assessment. Patients with rheumatic MS or ≥moderate mitral regurgitation (MR) were excluded. The primary endpoint was a reduction in the invasive mitral gradient by ≥50% without significant (≥moderate) MR. Fifteen patients underwent MVL between 2021 and 2023 with a mean age of 74 ± 9 years; 53% were female, with a mean STS score of 10% ± 0.1%. Following MVL, there was a reduction in the invasively measured mean trans-mitral gradient compared to baseline (14 mmHg vs. 6 mmHg; p < 0.05). The primary endpoint was achieved in 8 patients (53%) with no major procedural complications. At follow-up (median 90 days, IQR 58-115 days), 14 (93%) patients reported improved symptoms from New York Heart Association (NYHA) Class III-IV to NYHA Class I-II (p < 0.01) with stable echo-derived mean gradient (7.7 mmHg ± 2 mmHg vs. 8.4 mmHg ± 2.9 mmHg (p = 0.7). In selected patients with symptomatic inoperable calcific MS, MVL was safe and associated with significant short-term clinical and hemodynamic improvement. MVL may represent a new compassionate therapy for this challenging cohort. Further studies are needed to determine the long-term outcomes and help define the role of IVL technology in treating calcific valvular conditions.

Severe heart failure and intracardiac thrombosis: going beyond the appearance for diagnosis and treatments.

We describe the case of a 45-year-old female affected by asthma and nasal polyposis who presented to the emergency department because of worsening dyspnea and paresthesia of the left lower limb. Comprehensive instrumental examinations revealed the presence of severe left ventricle dysfunction, intra-cardiac thrombus, deep vein thrombosis, pulmonary embolism, lung infiltrates, polyserositis, and neurological involvements. Finally, the patient was diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA), formerly Churg-Strauss syndrome, a rare vasculitis of small-medium blood vessels with several organ involvements. Treatment with anticoagulants, corticosteroids, and cyclophosphamide led to a significant clinical improvement. However, a subcutaneous cardiac defibrillator was implanted because of the persistence of severe left ventricular dysfunction and the high cardiovascular risk phenotype. Indeed, several cardiac manifestations may occur in EGPA, particularly in patients with anti-neutrophil cytoplasmic antibody-negative disease. Therefore, clinicians should have high clinical suspicion because cardiac involvement in EGPA results in a poor prognosis if not diagnosed and adequately treated.

Evaluation of the efficacy and safety of cold laser (Diode 808 nm) therapy in the treatment of localized plaque psoriasis: clinical, dermoscopic and ultrastructural study

Background Psoriasis is a chronic, recurring, and immune-mediated inflammatory skin disease. Throughout the period of the last few decades, phototherapy has become widely used in treating stable psoriatic lesions. For the treatment of psoriasis, several light/laser therapies with distinct modes of action have been developed. Cold laser therapy might be an effective therapeutic choice for localized plaque psoriasis. Objective To assess the safety and efficacy of cold laser therapy clinically and microscopically in localized plaque psoriasis treatment. Patients and methods 40 patients with localized mild plaque psoriasis were selected from the Dermatology and Venereology outpatient clinic–Tanta University Hospitals and enrolled in the clinical trial. They were treated by cold laser 808 nm wavelength (Endolaser 422, Enraf–nonious B.V. Rotterdam, Netherlands) one session for 10 min on each plaque twice weekly separated by 2 days until clinical cure or for a maximum of 8 weeks. Evaluation was done immediately after the last session by taking the average of three blinded dermatologists of the photos, the modified Psoriasis Area and Severity Index [mPASI], dermoscopic examination, patients’ satisfaction scale and histopathological and electron microscopic examination of punch biopsy specimens taken before and after the end of treatment from psoriatic lesions in four patients only. Results There was a statistically significant clinical improvement after the end of treatment compared with before treatment as 16 patients (40%) showed excellent improvement, 8 patients (20%) showed good improvement, 9 patients (22.5%) showed mild improvement, and 7 patients (17.5%) showed poor improvement. As regard mPASI, a statistically significant decrease in mPASI was found after the end of treatment (P&lt;0.001). Regarding dermoscopic examination, a statistically significant reduction in the percentage of patients showing dermoscopic red dots and white scales after the end of treatment (P&lt;0.01). As regard the patients’ satisfaction scale, 82.5% of patients were satisfied from the results. Histopathological and ultrastructural evaluation revealed normalization of the psoriatic microscopic changes with cold laser. Conclusion The use of cold laser therapy for the management of localized mild plaque psoriasis is safe, tolerable, effective, and can be used as an alternative therapy for psoriasis.

Bladder instillations versus onabotulinumtoxinA injection for interstitial cystitis/bladder pain syndrome: A randomized clinical trial

Interstitial cystitis/bladder pain syndrome is an unpleasant sensation related to the bladder with lower urinary tract symptoms lasting more than six weeks, unrelated to an otherwise identifiable cause. The etiology is likely multifactorial including urothelial abnormalities, neurogenic pain upregulation, and potentially bladder and vaginal microbiome alterations. Despite treatment effectiveness of both bladder instillations and intradetrusor onabotulinumtoxinA injection for this condition, a head-to-head comparison has not been performed. To compare the efficacy of bladder instillations and intradetrusor onabotulinumtoxinA injection for treatment of interstitial cystitis/bladder pain syndrome. Patients with O'Leary-Sant (OLS) questionnaire scores of ≥ 6, meeting clinical criteria for interstitial cystitis/bladder pain syndrome, and desiring procedural management were randomized to bladder instillations or intradetrusor onabotulinumtoxinA injection. The primary outcome was the difference in OLS scores at 2 months post-treatment between groups. Secondary outcomes included evaluation of sexual function, physical/mental health status, pain, patient satisfaction, treatment perception, retreatment, and adverse event rates. 47 patients were analyzed with 22 randomized to bladder instillations and 25 to onabotulinumtoxinA injection. There were no differences in demographic and clinical characteristics between groups. From baseline to 2 months post-treatment, there was a decrease in OLS subscales in all patients (Interstitial Cystitis Symptom Index (ICSI) -6.3 (CI -8.54, -3.95), p<.0001; Interstitial Cystitis Problem Index (ICPI) -5.9 (CI -8.18, -3.57), p<.0001). At 2 months post-treatment, patients in the onabotulinumtoxinA group had significantly lower OLS scores compared to those in the bladder instillation group (ICSI 6.3 ± 4.5 [onabotulinumtoxinA] versus 9.6 ± 4.2 [instillation], p=.008; ICPI 5.9 ± 5.1 [onabotulinumtoxinA] versus 8.3 ± 4.0 [instillation], p=.048). The difference in OLS scores between groups did not persist at 6-9 months post-treatment. There were no statistically significant differences between baseline and post-treatment time points for the remaining questionnaires. Eight percent of patients who received onabotulinumtoxinA injection experienced urinary retention requiring self-catheterization. Patients who underwent onabotulinumtoxinA injection were significantly less likely to receive retreatment within 6-9 months compared to patients who received bladder instillations (relative risk 13.6; 95% CI, 1.92-96.6; P=.0002). There were no differences between groups regarding patient satisfaction, perception of treatment convenience, or willingness to undergo retreatment. Both onabotulinumtoxinA injection and bladder instillations are safe, effective treatments for patients with interstitial cystitis/bladder pain syndrome, with significant clinical improvement demonstrated at 2 months post-treatment. Our findings suggest that intradetrusor onabotulinumtoxinA injection is a more effective procedural treatment for this condition than bladder instillation therapy and associated with decreased rates of retreatment.

Endovascular penile revascularization improves erectile dysfunction in patients with penile arterial insufficiency

In most institutions, patients with erectile dysfunction due to penile arterial insufficiency are offered palliative treatments like vacuum constrictor devices, intraurethral alprostadil, intracavernosal injection of prostaglandins, and/or implantation of penile prosthesis when these patients can be treated by endovascular penile revascularization. 50% of patients with erectile dysfunction are non-responders to phosphodiesterase-5 inhibitors. 70% of non-responders to phosphodiesterase-5 inhibitors have penile arterial insufficiency that can be treated with endovascular penile revascularization. Patients who are non-responders to phosphodiesterase-5 inhibitors should be screened for penile arterial insufficiency using penile duplex scan. If penile artery peak systolic velocity is &lt;35 cm/s, then arterial insufficiency is suspected, and computed tomography (CT) angiogram is obtained to confirm presence of significant stenosis in iliac-pedundle-penile arterial system. Patients with penile arterial insufficiency should be offered endovascular penile revascularization. This minimally invasive procedure has minimal perioperative complications (&lt;1%) and has significant clinical improvement in erectile function in &gt;60% of patients at 12 months. Endovascular penile revascularization is safe and has long term clinical improvement in erectile function. This minimally invasive procedure can result in improved erectile function and preserves penile size and shape in most non-responders to phosphodiesterase-5 inhibitors.

Effectiveness of DialBetesPlus, a self-management support system for diabetic kidney disease: Randomized controlled trial

We evaluated the effectiveness of a mobile health (mHealth) intervention for diabetic kidney disease patients by conducting a 12-month randomized controlled trial among 126 type 2 diabetes mellitus patients with moderately increased albuminuria (urinary albumin-to-creatinine ratio (UACR): 30-299 mg/g creatinine) recruited from eight clinical sites in Japan. Using a Theory of Planned Behavior (TPB) behavior change theory framework, the intervention provides patients detailed information in order to improve patient control over exercise and dietary behaviors. In addition to standard care, the intervention group received DialBetesPlus, a self-management support system allowing patients to monitor exercise, blood glucose, diet, blood pressure, and body weight via a smartphone application. The primary outcome, change in UACR after 12 months (used as a surrogate measure of renal function), was 28.8% better than the control group’s change (P = 0.029). Secondary outcomes also improved in the intervention group, including a 0.32-point better change in HbA1c percentage (P = 0.041). These improvements persisted when models were adjusted to account for the impacts of coadministration of drugs targeting albuminuria (GLP-1 receptor agonists, SGLT-2 inhibitors, ACE inhibitors, and ARBs) (UACR: −32.3% [95% CI: −49.2%, −9.8%] between-group difference in change, P = 0.008). Exploratory multivariate regression analysis suggests that the improvements were primarily due to levels of exercise. This is the first trial to show that a lifestyle intervention via mHealth achieved a clinically-significant improvement in moderately increased albuminuria.

Real-Life Effectiveness and Safety of Guselkumab in Patients with Psoriasis Who Have an Inadequate Response to Ustekinumab: A 3-Year Multicenter Study.

Background: Guselkumab is the first approved human IgG1λ monoclonal antibody selectively targeting the p19 subunit of IL23. Its effectiveness and safety were widely reported by clinical trials. However, these results must be confirmed in real life since its safety deals with more complicated subjects with respect to trials. Currently, real-life data on the use of guselkumab following treatment failure with ustekinumab are limited, and existing studies usually show a small cohort and/or a reduced follow-up period. In this context, the aim of our study was to evaluate the use of guselkumab in patients who previously did not respond to ustekinumab after up to 3 years of treatment. Methods: A multicenter retrospective study was performed. The study enrolled patients affected by moderate-to-severe plaque psoriasis undergoing treatment with guselkumab who were attending the Psoriasis Center of nine different centers in the Campania region of Italy. Demographic and clinical features were collected for each patient at baseline. Moreover, data on psoriasis severity and adverse events (AEs) were collected at each follow-up visit (week (W)16-W36-W52-W104-W156). Results: A total of 112 patients (70 male, 62.5%; mean age 54.8 ± 11.7 years old) were enrolled. Of these, 48 (42.9%), 34 (30.4%), and 16 (14.3%) reached 1, 2, and 3 years, respectively, of follow-up under guselkumab. A statistically significant clinical improvement was observed since W16, and sustained effectiveness was reported at each timepoint up to W156. No serious AEs were collected. Moreover, a sub analysis on the body mass index, involvement of difficult-to-treat areas, and presence of psoriatic arthritis (PsA) showed that the presence of PsA or palmoplantar psoriasis was associated with a reduced clinical improvement at W16 and W36, without differences from W52. In contrast, the efficacy of guselkumab does not seem to be affected by the BMI, involvement of fingernails, or location in the genital or scalp area. Conclusions: To sum up, our long-term real-life multicenter retrospective study confirmed the efficacy and safety of guselkumab following ustekinumab discontinuation up to 156 weeks of treatment.

Adaptive resistance to cefiderocol in carbapenem-resistant Acinetobacter baumannii (CRAB): microbiological and clinical issues

ObjectivesDetermining the best available therapy for carbapenem-resistant Acinetobacter baumannii (CRAB) infections is a challenge. Cefiderocol is an attractive alternative drug effective against many resistance mechanisms in Gram-negative bacteria. However, its place in the treatment of Acinetobacter baumannii infections remains unclear and much debated, with contradictory results. MethodsWe describe here the case of a 37-year-old man with ventilator-associated bacteraemic CRAB pneumonia in an intensive care unit. He was initially treated with a combination of colistin and tigecycline, and was then switched onto colistin and cefiderocol. We then used a new accessible protocol to test 30 CRAB isolates (OXA-23/OXA-24/OXA-58/NDM-1) for adaptive resistance to cefiderocol (ARC) after exposure to this drug. ResultsAfter clinical failure with the initial combination, we noted a significant clinical improvement in the patient on the second combination, leading to clinical cure. No ARC was detected in the two OXA-23 case-CRAB isolates. All NDM-1 CRAB isolates were resistant to cefiderocol in standard tests; the OXA-23, OXA-24 and OXA-58 CRAB isolates presented 84.2 %, 50 % and 0 % ARC, respectively. ConclusionsARC is not routinely assessed for CRAB isolates despite frequently being reported in susceptible isolates (69.2 %). Subpopulations displaying ARC may account for treatment failure, but this hypothesis should be treated with caution in the absence of robust clinical data. The two main findings of this work are that (i) cefiderocol monotherapy should probably not be recommended for OXA-23/24 CRAB infections and (ii) the characterisation of carbapenemases in CRAB strains may be informative for clinical decision-making.

Interpretation of PD-L1 expression in gastric cancer: summary of a consensus meeting of Korean gastrointestinal pathologists.

Nivolumab plus chemotherapy in the first-line setting has demonstrated clinical efficacy in patients with human epidermal growth factor receptor 2-negative advanced or metastatic gastric cancer, and is currently indicated as a standard treatment. Programmed death-ligand 1 (PD-L1) expression is an important biomarker for predicting response to anti-programmed death 1/PD-L1 agents in several solid tumors, including gastric cancer. In the CheckMate-649 trial, significant clinical improvements were observed in patients with PD-L1 combined positive score (CPS) ≥ 5, determined using the 28-8 pharmDx assay. Accordingly, an accurate interpretation of PD-L1 CPS, especially at a cutoff of 5, is important. The CPS method evaluates both immune and tumor cells and provides a comprehensive assessment of PD-L1 expression in the tumor microenvironment of gastric cancer. However, CPS evaluation has several limitations, one of which is poor interobserver concordance among pathologists. Despite these limitations, clinical indications relying on PD-L1 CPS are increasing. In response, Korean gastrointestinal pathologists held a consensus meeting for the interpretation of PD-L1 CPS in gastric cancer. Eleven pathologists reviewed 20 PD-L1 slides with a CPS cutoff close to 5, stained with the 28-8 pharmDx assay, and determined the consensus scores. The issues observed in discrepant cases were discussed. In this review, we present cases of gastric cancer with consensus PD-L1 CPS. In addition, we briefly touch upon current practices and clinical issues associated with assays used for the assessment of PD-L1 expression in gastric cancer.

Repeat Discectomy or Instrumented Surgery for Recurrent Lumbar Disk Herniation: An Overview of French Spine Surgeons' Practice.

Retrospective multicenter cohort study. Recurrent lumbar disc herniation (ReLDH) is a common condition requiring surgical intervention in a large proportion of cases. Evidence regarding the appropriate choice between repeat microdiscectomy (RD) and instrumented surgery (IS) is lacking. To understand the indications for either of the procedures and compare the results, we aimed to provide an overview of spine surgeon practice in France. This retrospective, multicenter analysis included adults who underwent surgery for ReLDHs between December 2020 and May 2021. Surgeons were asked which of the following factors determined their therapeutic choice: radio-clinical considerations, non-discal anatomical factors, patient preference, or surgeon background. Data on preoperative clinical status and radiologic findings were collected. Patient-reported outcome measures (PROMs) were assessed and compared using propensity scores preoperatively and at 3 and 12 months postoperatively. The study included 150 patients (72 IS and 78 RD). Radioclinical elements, anatomical data, patient preferences, and surgeon background influenced the choice of RD in 57.7%, 1.3%, 25.6%, and 15.4% of the cases, respectively, and IS in 34.7%, 6.9%, 13.9%, and 44.5% of the cases, respectively. At 12 months, patient satisfaction, return to work, and changes in PROMs were not significantly different between the groups. The decision-making process included both objective and subjective factors, resulting in patient satisfaction in 80.3% to 81.5% of cases, with significant clinical improvement in radicular symptoms in 75.8% to 91.8% of cases, and quality of life in 75.8% to 84.9% of cases, depending on the procedure performed.

The role of colchicine in the management of COVID-19: a Meta-analysis

BackgroundThe Coronavirus disease 2019 (COVID-19) pandemic has robustly affected the global healthcare and economic systems and it was caused by coronavirus-2 (SARS-CoV-2). The clinical presentation of the disease ranges from a flu-like illness to severe pneumonia and death. Till September 2022, the cumulative number of cases exceeded 600 million worldwide and deaths were more than 6 million. Colchicine is an alkaloid drug that is used in many autoinflammatory conditions e.g., gout, familial Mediterranean fever, and Behçet’s syndrome. Colchicine inhibits the production of superoxide and the release of interleukins that stimulate the inflammatory cascade. Colchicine decreases the differentiation of myofibroblast and the release of fibrotic mediators including transforming growth factor (TGF-β1) that are related to the fibrosis. Moreover, colchicine has been used to traet viral myocarditis caused by CMV or EBV, interstitial pneumonia, and pericarditis resulting from influenza B infection. Additionally, colchicine is considered safe and affordable with wide availability.ObjectiveThe aim of the current study was to assess the evidence of colchicine effectiveness in COVID-19 treatment.MethodsA comprehensive review of the literature was done till May 2022 and yielded 814 articles after ranking the articles according to authors and year of publication. Only 8 clinical trials and cohort studies fulfilling the inclusion criteria were included for further steps of data collection, analysis, and reporting.ResultsThis meta-analysis involved 16,488 patients; 8146 patients in the treatment group and 8342 patients in the control group. The results showed that colchicine resulted in a significant reduction in the mortality rate among patients received colchicine in comparison with placebo or standard care (RR 0.35, 95%CI: 0.15–0.79). Colchicine resulted in a significant decrease in the need for O2 therapy in patients with COVID-19 (RR 0.07, 95%CI 0.02–0.27, P = 0.000024). However, colchicine had no significant effect on the following outcomes among COVID-19 patients: the need for hospitalization, ICU admission, artificial ventilation, and hospital discharge rate. Among the PCR confirmed COVID-19 patients, colchicine decreased the hospitalization rate (RR 0.75, 95%CI 0.57–0.99, P = 0.042). However, colchicine had no effect on mortality and the need for mechanical ventilation among this subgroup.ConclusionColchicine caused a significant clinical improvement among COVID-19 patients as compared with the standard care or placebo, in terms of the need for O2, and mortality. This beneficial effect could play a role in the management of COVID-19 especially severe cases to decrease need for oxygen and to decrease mortality among these patients.

Fluctuation of Disease Severity and Quality of Life Applying Intra-lymphatic Immunotherapy for Patients with Seasonal Allergic Rhinitis

Allergen-specific immunotherapy is the only disease-modifying treatment for IgE-mediated allergic disorders. Intra lymphatic immunotherapy (ILIT) is an efficacious and time-saving alternative to subcutaneous immunotherapy (SCIT). This study aimed to evaluate the effects and safety of ILIT in patients with moderate to severe allergic rhinitis. &#x0D; In this clinical trial, patients between 18 and 65 years old with moderate to severe allergic rhinitis were enrolled. They received monthly intra-lymphatic inguinal injections of an active allergen (1000 SQ-U Salsola kali pollen). Their clinical symptoms were assessed before and four weeks after treatments. The clinical signs were also evaluated during two consecutive pollination seasons and the following non-pollination season in April.&#x0D; No moderate or severe reactions were recorded following ILIT treatment. Lymph node enlargement, angioedema/urticaria, and local itching were seen instantly after injection. Patients who received ILIT experienced a significant clinical improvement in self-recorded seasonal allergic symptoms after the treatments, compared to themselves before ILIT. Furthermore, their quality of life significantly improved.&#x0D; This study suggests ILIT with Salsola-pollen extract may decrease symptoms of allergic rhinitis. It was safe and did not cause any crucial complications.&#x0D;