Standard Treatment Protocol Research Articles

Association of Inflammatory Markers With Disease Progression and the Severity of COVID-19.

Introduction InDecember 2019, there was a massive outbreak of viral pneumonia, which had a high case fatality rate. Genetic sequencing of the virus showed similarity with severe acute respiratory syndrome coronavirus (SARS-CoV). It was later named novel coronavirus 2019 while the disease it caused was given the nomenclature of COVID-19. This deadly pneumonia outbreak was declared a pandemic by the World Health Organization (WHO). Aim To derive the strength of the correlation between blood levels of various inflammatory markers with the severity of COVID-19 pneumonia in patients affected with novel coronavirus 2019. Materials and methodology A prospective study was conducted on 300 confirmed cases of COVID-19 infection from August 2020 to July 2021 in SSG Hospital, Vadodara. Diagnosis of patients as confirmed cases of COVID-19 infection was done according to the WHO interim guidance for COVID-19. Their inflammatory markers were done for this study. All COVID-19-positive patients who had given negative consent for enrollment were excluded from the study. Patients were classified based on the severity of acute respiratory distress syndrome (ARDS). Comprehensive medical record information, encompassing biodata, clinical symptoms, comorbidities, and laboratory investigations, was systematically collected. Patients were given the standard treatment protocol as per guidelines. Patients were subjected to detailed investigations comprising complete blood counts and inflammatory markers like C-reactive protein (CRP), lactate dehydrogenase (LDH), serum ferritin, and D-dimer. Patients were further investigated by chest X-ray (posteroanterior view) or high-resolution computed tomography of the thorax. Results A total of 300 confirmed cases of COVID-19 infection were included in this study. Most of them were males (52%) with a mean age of 51 years and 48% were females with a mean age of 55 years. The majority of patients(40%) did not have ARDS, 23.3% of patients had mild, 16.7% of patients had moderate, and 20% of patients had severe ARDS. Higher CRP levels, serum ferritin, and serum D-dimer were significantly associated with the severity of COVID-19 infection as compared to those having no symptoms (p < 0.05). Increased levels were associated with severe clinical manifestations of COVID-19. The sensitivity of CRP is 69% and specificity is 100% as a diagnostic marker for COVID-19 pneumonia in terms of ARDS. The sensitivity of ferritin is 88% and specificity is 81% as a diagnostic marker for COVID-19 pneumonia in terms of ARDS. The sensitivity of D-dimer is 94% and specificity is 89% as a diagnostic marker for COVID-19 pneumonia in terms of ARDS. The sensitivity of LDH is 93% and specificity is 84% as a diagnostic marker for COVID-19 pneumonia in terms of ARDS. Conclusions Current evidence from our study showed that higher levels of inflammatory markers such as CRP, LDH, D-dimer, and ferritin are associated with the severity of COVID-19 in terms of ARDS and thus could be used as significant prognostic factors of the disease.These indicators might support clinical decisions to identify highfatality casesand poor diagnosis in the initial admission phase.

Aortic arch blood flow measurements as a predictor of successful ECMO weaning in cardiogenic shock

ObjectiveAcute cardiogenic shock is a life-threatening condition with mortality rates of up to 50%. If conventional therapy fails, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) therapy has emerged to a promising alternative for temporary cardiac and respiratory support in specialized centers. However, it is only a bridge to recovery, final decision, heart transplantation or the permanent implantation of a left ventricular assist device. Therefore, the identification of the optimum weaning time point is challenging, and standardized weaning protocols are rare. MethodsIn this explorative pilot study, we evaluated the potential benefit of blood flow measurements in the aortic arch using an ultrasonic cardiac output monitor (USCOM) for the primary endpoint of successful VA-ECMO weaning. 12 patients under VA-ECMO therapy for acute cardiogenic shock and a hemodynamic condition which qualified for a stepwise weaning process were included in this study. Main exclusion criterion was the presence of additional venting therapy for left ventricular unloading, e.g. Impella. Statistical comparisons were performed using the Mann-Whitney test and corrected for multiple testing by the Holm-Sidak method. ResultsPeak velocity of flow in the aortic arch showed a positive correlation with weaning success independent of ECMO flow (weaning success vs. failure: 0.75 vs. 0.35 m/s (low ECMO support), p = 0.049), whereas we identified only a trend for mean pressure gradient, minute distance and stroke volume index. ConclusionWe hypothesize, that USCOM might provide an additive benefit to conventional strategies in its ability to predict successful VA-ECMO weaning and prevent pulmonary congestion. Larger upcoming trials are required to address this relevant topic and provide standardized treatment protocols for optimized weaning in the future.

Laparoscopic Treatment of Perforated Peptic Ulcer: A Propensity Score-Matched Comparison of Interrupted Stitches Repair versus Knotless Barbed Suture.

Background: Peptic ulcers result from imbalanced acid production, and in recent decades, proton pump inhibitors have proven effective in treating them. However, perforated peptic ulcers (PPU) continue to occur with a persistent high mortality rate when not managed properly. The advantages of the laparoscopic approach have been widely acknowledged. Nevertheless, concerning certain technical aspects of this method, such as the best gastrorrhaphy technique, the consensus remains elusive. Consequently, the choice tends to rely on individual surgical experiences. Our study aimed to compare interrupted stitches versus running barbed suture for laparoscopic PPU repair. Methods: We conducted a retrospective study utilizing propensity score matching analysis on patients who underwent laparoscopic PPU repair. Patients were categorised into two groups: Interrupted Stitches Suture (IStiS) and Knotless Suture (KnotS). We then compared the clinical and pathological characteristics of patients in both groups. Results: A total of 265 patients underwent laparoscopic PPU repair: 198 patients with interrupted stitches technique and 67 with barbed knotless suture. Following propensity score matching, each group (IStiS and KnotS) comprised 56 patients. The analysis revealed that operative time did not differ between groups: 87.9 ± 39.7 vs. 92.8 ± 42.6 min (p = 0.537). Postoperative morbidity (24.0% vs. 32.7%, p = 0.331) and Clavien-Dindo III (10.7% vs. 5.4%, p = 0.489) were more frequently observed in the KnotS group, without any significant difference. In contrast, we found a slightly higher mortality rate in the IStiS group (10.7% vs. 7.1%, p = 0.742). Concerning leaks, no differences emerged between groups (3.6% vs. 5.4%, p = 1.000). Conclusions: Laparoscopic PPU repair with knotless barbed sutures is a non-inferior alternative to interrupted stitches repair. Nevertheless, further research such as randomised trials, with a standardised treatment protocol according to ulcer size, are required to identify the best gastrorraphy technique.

Non Indigenous Mammary Secretory Carcinoma of Parotid Gland - An Unusual Presentation.

Mammary analog secretory carcinoma (MASC) is a relatively rare, low-grade tumor affecting the salivary glands. We report a 62-year-old female who was diagnosed with MASC of the left parotid gland and underwent left Total conservative parotidectomy with condylectomy and reconstruction with right anterolateral free flap and left facial nerve (frontal branch) reconstruction with a cable graft. As there is no standard treatment protocol developed for the management of MASC, this report focuses on the various management options that have been followed to date.

Pharmacological therapies for height improvement in pubertal children with short stature

Short stature in puberty significantly affects the physical and mental health of adolescents. The continuous acceleration of skeletal maturation, caused by sex hormones during puberty, limits the time available for growth and poses a considerable challenge for the treatment of short stature. To date, there is still no standardized treatment protocol for this disorder. However, puberty is the last period to improve the final adult height. Currently, commonly used pharmacological treatments in clinical settings include recombinant human growth hormone, gonadotropin-releasing hormone analogs, and third-generation aromatase inhibitors. In recent years, personalized treatment aiming to improve the final adult height has become a key focus in clinical practice. This article provides a comprehensive summary of research on pharmacological therapies for height improvement in pubertal children with short stature, offering valuable insights for healthcare professionals.

Advancements in Periodontal Regeneration: A Comprehensive Review of Stem Cell Therapy.

Periodontal disease, characterized by inflammation and infection of the supporting structures of teeth, presents a significant challenge in dentistry and public health. Current treatment modalities, while effective to some extent, have limitations in achieving comprehensive periodontal tissue regeneration. This comprehensive review explores the potential of stem cell therapy in advancing the field of periodontal regeneration. Stem cells, including mesenchymal stem cells (MSCs) and induced pluripotent stem cells (iPSCs), hold promise due to their immunomodulatory effects, differentiation potential into periodontal tissues, and paracrine actions. Preclinical studies using various animal models have revealed encouraging outcomes, though standardization and long-term assessment remain challenges. Clinical trials and case studies demonstrate the safety and efficacy of stem cell therapy in real-world applications, especially in personalized regenerative medicine. Patient selection criteria, ethical considerations, and standardized treatment protocols are vital for successful clinical implementation. Stem cell therapy is poised to revolutionize periodontal regeneration, offering more effective, patient-tailored treatments while addressing the systemic health implications of periodontal disease. This transformative approach holds the potential to significantly impact clinical practice and improve the overall well-being of individuals affected by this prevalent oral health concern. Responsible regulatory compliance and a focus on ethical considerations will be essential as stem cell therapy evolves in periodontal regeneration.

The CHA2DS2-Vasc Score's Role as A Standalone Predictor for Suboptimal Reperfusion and Short-Term Mortality Post Primary PCI in Individuals Diagnosed with Acute ST-Segment Elevation Myocardial Infarction

Background: The CHA2DS2-VASc score is an established clinical prediction tool for assessing stroke risk in patients with atrial fibrillation. However, its potential utility in predicting outcomes following primary percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) has not been extensively explored. The no-reflow phenomenon and in-hospital mortality are critical endpoints in the management of STEMI patients undergoing PCI. Objective: This study aimed to evaluate the independent predictive value of the CHA2DS2-VASc score for suboptimal reperfusion and short-term mortality in patients with acute STEMI undergoing primary PCI. Methods: In a prospective cohort study involving 116 patients with confirmed STEMI at the National Institute of Cardiovascular Diseases in Karachi, participants were categorized based on their CHA2DS2-VASc score into low (&lt;3) and high (≥3) risk groups. Primary PCI was performed following standard treatment protocols, and variables such as initial TIMI flow, thrombus grade, and lesion complexity were documented. Statistical analysis, including multivariate regression, was conducted using SPSS Version 25. Results: Patients with a high CHA2DS2-VASc score (≥3) exhibited a significantly increased risk of no-reflow (p-value range 0.00-0.03) and in-hospital mortality (11.1%) compared to those with a low score (&lt;3; 1.3% mortality). Other significant findings included an association between high CHA2DS2-VASc scores and larger stent lengths (28.75±5.67 mm), smaller stent diameters (2.69±0.6 mm), higher creatinine levels (1.00±0.202 mg/dL), and increased incidence of diabetes mellitus (36.1%). The odds ratio for mortality associated with a high CHA2DS2-VASc score was 1.58 (95% CI: 1.14–2.13, p-value &lt; 0.00). Conclusion: The CHA2DS2-VASc score is a significant independent predictor of both no-reflow post-PCI and short-term in-hospital mortality in STEMI patients. These findings suggest the score's potential role in the pre-PCI risk stratification, which could guide clinical decision-making and potentially improve patient outcomes.

Personalized Versus Precision Nanomedicine for Treatment of Ovarian Cancer.

The response to treatment is substantially varied between individual patients with ovarian cancer. However, chemotherapy treatment plans rarely pay sufficient attention to the mentioned factors. Instead, standardized treatment protocols are usually employed for most ovarian cancer patients. Variations in an individual's sensitivity to drugs significantly limit the effectiveness of treatment in some patients and lead to severe toxicities in others. In the present investigation, a nanotechnology-based approach for personalized treatment of ovarian carcinoma (the most lethal type of gynecological cancer) constructed on the individual genetic profile of the patient's tumor is developed and validated. The expression of predefined genes and proteins is analyzed for each patient sample. Finally, a mixture of the complex nanocarrier-based targeted delivery system containing drug(s)/siRNA(s)/targeted peptide is selected from the pre-synthesized bank and tested in vivo on murine cancer model using cancer cells isolated from tumors of each patient. Based on the results of the present study, an innovative approach and protocol for personalized treatment of ovarian cancer are suggested and evaluated. The results of the present study clearly show the advantages and perspectives of the proposed individual treatment approach.

Equine uveitis: Outcome and adverse effects after one or two intravitreal low-dose gentamicin injections.

Uveitis is common in horses, potentially turning chronic (persistent or recurrent) resulting in impaired vision or blindness. All mainstay therapeutics aims at controlling inflammation, but long-term or lifelong treatment is often needed with possibly severe side effects. Therefore, intravitreal injections with low-dose gentamicin (IVGI) have been used in attempt to give a long-lasting result with potentially less side effects. To retrospectively assess outcome and long-term complications following one or two low-dose IVGI in Swedish horses with chronic uveitis. Retrospective case series. Medical records of horses diagnosed with uveitis examined at the Equine Clinic of the University Animal Hospital of Sweden between 2016 and 2021 were reviewed. Inclusion criteria were horses with a diagnosis of chronic uveitis that were treated with 4 mg IVGI. After injection, tapering doses of anti-inflammatory medications were administered. Due to persistence or recurrence of uveitis despite IVGI, some horses received a second injection. A positive outcome was defined as controlled uveitis, despite no or minimal anti-inflammatory medication. 32 eyes (29 horses) were included. Based on clinical evaluation, uveitis was classified as anterior (91%) or panuveitis (9%). 10 eyes were treated with IVGI twice. A positive outcome was observed in 13/32 eyes (41%). Inflammation in 9/32 eyes was controlled after the first, and in 4/10 eyes after the second IVGI treatment. Long-term complications included retinal degeneration in seven eyes, and mature cataracts in five eyes. Enucleations were performed in 14/32 eyes, due to lack of favourable response of IVGI, or due to complications, that is, glaucoma, corneal ulceration, and/or corneal mineralisation. One horse was euthanised due to painful bouts of inflammation in both eyes despite treatment. Small sample size, retrospective design with no control group, no histopathology performed, infrequent sampling for Leptospira and no standardised treatment protocol after the IVGI. In this group of Swedish horses, predominantly diagnosed clinically with anterior uveitis, a positive outcome was observed in 41% of eyes following one or two low-dose IVGI. Retinal degeneration in the visual streak was observed in 22% of eyes, which is a higher proportion of this complication than previously described.

Endothelial Mitochondria Transfer to Melanoma Induces M2-Type Macrophage Polarization and Promotes Tumor Growth by the Nrf2/HO-1-Mediated Pathway.

Gynecologic tract melanoma is a malignant tumor with poor prognosis. Because of the low survival rate and the lack of a standard treatment protocol related to this condition, the investigation of the mechanisms underlying melanoma progression is crucial to achieve advancements in the relevant gynecological surgery and treatment. Mitochondrial transfer between adjacent cells in the tumor microenvironment regulates tumor progression. This study investigated the effects of endothelial mitochondria on the growth of melanoma cells and the activation of specific signal transduction pathways following mitochondrial transplantation. Mitochondria were isolated from endothelial cells (ECs) and transplanted into B16F10 melanoma cells, resulting in the upregulation of proteins associated with tumor growth. Furthermore, enhanced antioxidation and mitochondrial homeostasis mediated by the Sirt1-PGC-1α-Nrf2-HO-1 pathway were observed, along with the inhibition of apoptotic protein caspase-3. Finally, the transplantation of endothelial mitochondria into B16F10 cells promoted tumor growth and increased M2-type macrophages through Nrf2/HO-1-mediated pathways in a xenograft animal model. In summary, the introduction of exogenous mitochondria from ECs into melanoma cells promoted tumor growth, indicating the role of mitochondrial transfer by stromal cells in modulating a tumor's phenotype. These results provide valuable insights into the role of mitochondrial transfer and provide potential targets for gynecological melanoma treatment.

Genomic comparison of urothelial mucinous adenocarcinoma and colorectal mucinous adenocarcinoma biomarkers and therapeutic implications.

650 Background: Urothelial mucinous adenocarcinoma (UC-MUC-AC), arising from the urothelium, is a rare condition (&lt;2%), typically presenting at an advanced stage with an unfavorable prognosis. The lack of a standard treatment protocol adds complexity, requiring the extension of treatments from UC or organ-specific MUC-AC such as colorectal. Notably, UC-AC bears a histopathological resemblance to intestinal tumors, constituting the predominant subtype. Alternatively, treatment decisions based on gene expression similarities in lieu of histological similarities are an evolving concept in rare cancers. This is an unexplored area in UC-MUC-AC treatment, prompting our hypothesis that an all-encompassing genomic profile could reveal analogous biomarkers shared with CRC-MUC-AC. Methods: Three techniques: DNA sequencing, RNA sequencing (WTS), and immunohistochemistry (IHC) sequencing (protein) with varying measures for gene expression were analyzed at Caris Life Sciences in Phoenix, AZ. Histopathology was used to categorize five cancer site groups: (1) UC arising in the bladder, ureter, urethra, or renal pelvis with any transitional cell carcinoma (TCC)-non-MUC-nonAC [N156 samples], (2) UC nonTCC-nonMUC-AC [N83], (3) UC-MUC-AC [N16], (4) CRC-MUC-AC [N3100] and (5) CRC nonMUC-AC [N38205]. Our primary aim was to determine which group was closest to Group 3, our control. Our secondary aim was to determine if Group 2 was genetically closer to Group 1 or 5. Only genes with positive expression were included in the cluster analysis. ANOVA analysis was conducted to further explore the relationships between the groups. A log transformation was performed to achieve normality. To further investigate pairwise comparisons, a post hoc Dunnett test was employed. Results: In our first analysis, Group 3 UC-MUC-AC gene expression ratio was predominately associated with UC Groups 1 &amp; 2 (24 of 33), and farther to CRC Groups 4 &amp; 5 (9/33) (all p-values &gt;0.05). In the second analysis, the ANOVA overall model comparing gene expression between the histological groups 1, 2 &amp; 5 was statistically significant (p=0.0018). The Dunnett test revealed a farther difference between Group 2, UC nonTCC-nonMUC adenocarcinoma, and 5, CRC non-MUC-AC (p-value =0.001), but closest between Group 2 and 1, UC-TCC-nonMUC-nonAC (p =0.100). Conclusions: Our findings indicate that next-generation sequencing technology has the potential to aid in treatment decisions based on the site of origin, such as UC-AC, rather than relying on traditional histopathological descriptive approaches for extrapolating evidence from treatment protocols used for other cancer origins like CRC. Future research on artificial intelligence could aid physicians with more informed treatment decisions by providing additional insight into how closely tumors match cancer types' genomic and transcriptomic signatures.

Effectiveness of Peripheral Nerve Block in Terms of Search for a Standardized Treatment Protocol in Diabetic Foot Patients Using Anticoagulants: A Double-Center Study.

Lower-extremity amputation for a diabetic foot is mainly performed under general or central neuraxial anesthesia. Ultrasound-guided peripheral nerve block (PNB) can be a good alternative, especially for patients who require continuous anticoagulation treatment and patients with additional comorbidities. We evaluated bleeding due to PNB application in patients with diabetic foot receiving antiplatelet or anticoagulant therapy. Perioperative morbidity and mortality and the need for intensive care hospitalization were analyzed. This study included 105 patients with diabetic foot or debridement who underwent distal foot amputation or debridement between February and October 2020. Popliteal nerve block (17 mL of 5% bupivacaine and 3 mL of saline) and saphenous nerve block (5 mL of 2% lidocaine) were applied to the patients. Postoperative pain scores (at 4, 8, 12, and 24 hours) and complications due to PNB were evaluated. Intensive care admission and 1-month mortality were recorded. The most common diseases accompanying diabetes were hypertension and peripheral artery disease. No complications due to PNB were observed. Mean ± SD postoperative first analgesic need was determined to be 14.1 ± 4.1 hours. Except for one patient, this group was followed up without the need for postoperative intensive care. In 16 patients, bleeding occurred as leakage from the surgical area, and it was stopped with repeated pressure dressing. Mean ± SD patient satisfaction score was 8.36 ± 1.59. Perioperative mortality was not observed. Ultrasound-guided PNB can be an effective and safe anesthetic technique for diabetic patients undergoing distal foot amputation, especially those receiving antiplatelet or anticoagulant therapy and considered high risk.

Unilateral Lung Parenchymal Infiltrates with GGO &amp; Evolving Consolidation as Presenting Feature of Sporadic COVID-19 Pneumonia in Post Pandemic Era in a Patient with Acute Febrile Respiratory Illness

Sporadic COVID-19 cases will be predicted to occur in coming few years ahead as observed in previously known influenza virus related pandemics. Herd immunity due to natural infection and hybrid immunity after COVID-19 vaccination has played crucial role in waning of this pandemic. COVID-19 pneumonia has a very ‘typical’ radiological presentations, observed globally; classified as GGO and consolidations involving peripheral parts of lung, bilateral disease, predominantly pleural based areas initially and involves central portions as disease process advances. Such radiological presentations are never documented in history before this pandemic, which has helped in suspecting COVID-19 illness in cases with negative microbiological results initially and such illness were classified as SARI (severe acute respiratory illness). Cases with typical radiological features for COVID-19 with RT PCR positive results were defined as case of COVID-19 illness. Both the clinical scenarios were managed with similar protocol during hospitalization. COVID-19 case burden has significantly decreased in last one year since declaration of end of pandemic by WHO and now we are in post pandemic phase. Since beginnings of pandemic, many corona virus variants were emerged with variable infectivity, virulence, pathogenesis, mortality and morbidity. As pandemic is over, cases are rarely observed with lung involvement, COVID RT PCR testing, HRCT reporting’s in line with pandemic protocol and requirement of resources to treat these cases are less required and utilized today. In present case report, 32-year male, presented in outdoor unit with history of acute febrile respiratory illness with dry cough, high grade fever and chest tightness and chest discomfort of acute onset. HRCT thorax documented Pleural based, peripheral, unifocal or solitary opacity with predominant GGOs in right lower lobe with normal left lung. He is treated in indoor unit in line with community acquired pneumonia protocol and observed clinical worsening with four-fold raised in inflammatory markers. Oxygenation is worsened and raised IL-6, CRP and LDH has given clue to think towards COVID-19 etiology. Thorat swab for COVID-19 RT PCR is positive and managed according to protocol for COVID-19 illness. This is the only observed COVID-19 pneumonia case in last six months, in which; clinical-radiological patters were typical of pandemic illness of second wave of COVID-19 illness due to delta variant. Our case is the sporadic case reported with all clinical features of pandemic illness. We have suspected COVID-19 etiology in spite of ‘atypical unilateral lung involvement’ due to worsened clinical features and abnormally raised inflammatory markers with poor response to standard treatment protocol for community acquired pneumonia. High index of suspicion is must, and; timely interventions with use of rational treatment including remdesivir, heparin &amp; steroids combination during hospitalization has documented successful outcome. We recommend COVID-19 RT PCR testing in all community acquired cases nonresponding to standard guidelines to have timely diagnosis and treatment. Sporadic cases rare to occur, and they do occur for few years ahead of this end of pandemic due to virus variant, and we must quote ‘rare things are not rare to happen’.

Breakthrough in Blastic Plasmacytoid Dendritic Cell Neoplasm Cancer Therapy Owing to Precision Targeting of CD123.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic cancer originating from the malignant transformation of plasmacytoid dendritic cell precursors. This malignancy progresses rapidly, with frequent relapses and a poor overall survival rate, underscoring the urgent need for effective treatments. However, diagnosing and treating BPDCN have historically been challenging due to its rarity and the lack of standardized approaches. The recognition of BPDCN as a distinct disease entity is recent, and standardized treatment protocols are yet to be established. Traditionally, conventional chemotherapy and stem cell transplantation have been the primary methods for treating BPDCN patients. Advances in immunophenotyping and molecular profiling have identified potential therapeutic targets, leading to a shift toward CD123-targeted immunotherapies in both clinical and research settings. Ongoing developments with SL-401, IMGN632, CD123 chimeric antigen receptor (CAR) T-cells, and bispecific antibodies (BsAb) show promising advancements. However, the therapeutic effectiveness of CD123-targeting treatments needs improvement through innovative approaches and combinations of treatments with other anti-leukemic drugs. The exploration of combinations such as CD123-targeted immunotherapies with azacitidine and venetoclax is suggested to enhance antineoplastic responses and improve survival rates in BPDCN patients. In conclusion, this multifaceted approach offers hope for more effective and tailored therapeutic interventions against this challenging hematologic malignancy.

PROTECTIVE ROLE OF SAFFRON TO REDUCE INFLAMMATION AND IMPROVE CLINICAL MANIFESTATIONS IN ULCERATIVE COLITIS PATIENTS

Abstract BACKGROUND We studied saffron as an additional intervention to improve clinical manifestations of Ulcerative colitis (UC) patients. METHODS This is a study at Yazd university where 30 UC patients were randomly assigned to placebo (n=9), low (n=9, 25 mg), or high dose saffron (n=12, 50mg), two times a day for 8 weeks. Hemoglobin, platelet levels, CRP, ESR, and fecal calprotectin along with clinical data Simple Clinical Colitis Activity Index (SCCAI), Partial Mayo Score, and Hamilton Depression Anxiety Score (HDRS) were recorded at baseline and completion of treatment. For validation, we recruited 3 UC patients at Howard University who received 50mg of Saffron twice daily for 8 weeks, two underwent a wash-out period and received saffron for a second cycle. Inflammatory markers, CRP, stool calprotectin, and the cytokines from PMA/ionomycin stimulated PBMCs, at baseline and 8 weeks Saffron treatment were compared. 16S rDNA analysis was performed on stool DNA for gut microbiome. RESULTS In Yazd study of 30 patients, all participants completed the study successfully. The high dose group showed significant improvement in HDRS score (p=0.001), SCCAI (p=0.04), Partial Mayo score (p=0.01), fecal calprotectin (p=0.009), and CRP (p=0.001) compared to baseline. The low dose group also improved in HDRS score (p=0.01; Table 1, Fig 1). No adverse events were reported. In HU data, saffron improved Partial Mayo Score, health related quality of life and HDRS. Pro-inflammatory cytokines TNFα, INFγ, IL-6, IL-2, IL-17a decreased while anti-inflammatory IL-10, TGF-β increased. Fecal calprotectin levels of 228 μg/g and 169 μg/g decreased to 63 μg/g and 16 μg/g in two individual patients, respectively. After the wash-out period, fecal calprotectin increased. A second saffron treatment cycle reduced it again further validating the causal relationship. Saffron led to a decrease in gamma Proteobacteria, and enrichment in Ruminococcaceae. CONCLUSION This study demonstrates that saffron led to improvements in clinical response including reduction in partial Mayo scores, HDRS scores, and inflammatory markers such as fecal calprotectin and CRP. These findings suggest that the use of saffron supplements alongside standard treatment protocols may yield beneficial effects for individuals with UC. Table 1. Basic characteristics, clinical variables, and laboratory variables among the study participants in three arms of the clinical trial. Figure 1 Effect of Saffron on quality of life and Inflammatory markers.

Stepwise implementation of an enhanced recovery pathway for elective total hip arthroplasty in a Swiss hospital: a cohort study.

Enhanced recovery programs after total hip arthroplasty have been shown to reduce hospital length of stay without compromising results, but yet there is a lack of data for the Swiss population. Therefore, this retrospective cohort study evaluated whether similar positive effects on clinical outcomes are present in the context of the Swiss healthcare system. Patients who underwent elective primary total hip arthroplasty were analysed. The baseline group comprised 50 patients treated consecutively by one surgeon in 2013 according to the clinical practice guidelines. Another surgeon implemented a new standardised treatment protocol in April 2014. In January 2018, this protocol was followed by an enhanced recovery program that integrated all care providers at the hospital. The data of the baseline group (series 0) and four series of 50 patients each, two treated with the standardised treatment protocol (series 1-2) and two treated with the enhanced recovery program (series 3-4), were analysed. All patients had follow-ups at 6 weeks and 3 months after surgery. The primary outcomes were length of stay and discharge destination; the secondary outcomes were admission on the day of surgery (instead of one day prior), the use of urinary catheters, the administration of opioids, the difference between pre- and postoperative haemoglobin, blood transfusions, and adverse events within 3 months of surgery. The median length of stay was 10 days in the baseline group and only 5 days after the implementation of the standardised protocol and enhanced recovery program in series 4 (p <0.001). The percentage of patients discharged directly home was higher in series 4 than in the baseline group (84% vs. 66%, p = 0.085). Patients admitted to the hospital on the day of surgery increased from 2% in series 0 to 98% in series 4 (p <0.001). The use of urinary catheters was significantly higher in the baseline group (100% of patients) than in series 3 and 4 (0%) (p <0.001), and the number of patients who did not require opioids was significantly higher in series 4 than in series 0 (36% vs. 10%, p = 0.007). The median blood loss (500 ml vs. 300 ml, p <0.001), median difference in pre- and postoperative haemoglobin (29 g/dl vs. 25 g/dl, p = 0.145), and number of blood transfusions (5 vs. 2 p = 0.99) were higher in the baseline group than in series 4. The number of adverse events did not differ significantly between groups (p = 0.699). Almost all parameters examined in this study showed improvement, whereas the rate of adverse events was not affected and remained low. The presented data can be used as a benchmark, but details of these findings need to be confirmed in larger cohorts.

Adjuvant effect of antimicrobial photodynamic therapy (aPDT) in the treatment of diabetic foot ulcers: A case series.

This study aimed to evaluate the clinical evolution of patients with diabetic foot ulcer treated with antimicrobial photodynamic therapy (aPDT) using the Bates-Jensen (BJ) scale. A total of 21 patients were monitored, with an average age of 58 years. Patients underwent the standard treatment protocol of the institution, supplemented with aPDT utilizing 0.01% methylene blue (MB) and laser irradiation (660 nm, 100 mW, 6 J per point). Following aPDT, the lesions were protected with hydrofiber dressings containing silver. The Bates-Jensen Scale was employed at pre-treatment and post-aPDT sessions to assess lesion progression. The results demonstrated a significant difference between pre- and post-treatment values in the overall BJ score. The use of MB in aPDT proved to be an effective, safe, well-tolerated treatment with high patient adherence and the potential for implementation in the care of diabetic foot conditions.

Pain-free hospital implementation: a multidimensional intervention to improve pain management at Wallaga University Referral Hospital, Nekemte, Ethiopia

ObjectiveThis quality improvement project is aimed to increase pain free hospital implementation from 21.7 to 80% at Wallaga University Referral Hospital (WURH) from January 1, 2023 to June 30, 2023.MethodsHospital based interventional study was conducted at WURH. The Plan- Do-Study-Act (PDSA) cycle was used to test change ideas. A fishbone diagram and a driver diagram were used to identify root causes and address them. Major interventions included training of health professionals, initiation of pain as fifth vital sign, policy and protocol development, and conducting regular supportive supervision.ResultsUpon completion of the project, overall pain-free hospital implementation increased from baseline 21.7–88.7%. Implementation of pain as 5th the vital sign was increased from 15.4 to 92.3%. Regular audits of pain assessment and management increased from 27.3 to 81.8%. Two standardized treatment protocols or chronic and acute pains were developed from baseline zero. A focal person for Pain-free hospital implementation was assigned. More than 85% of healthcare providers were trained in pain assessment and management.ConclusionCompliance with pain-free hospital implementations was significantly improved in the study area. This was achieved through the application of multidimensional change ideas related to health professionals, standardized guidelines and protocols, supplies, and leadership. Therefore, we recommend providing regular technical updates & conducting a frequent clinical audit on pain management.

Altered tumor signature and T-cell profile after chemotherapy reveal new therapeutic opportunities in high-grade serous ovarian carcinoma.

Chemotherapy combined with debulking surgery is the standard treatment protocol for high-grade serous ovarian carcinoma (HGSOC). Nonetheless, a significant number of patients encounter relapse due to the development of chemotherapy resistance. To better understand and address this resistance, we conducted a comprehensive study investigating the transcriptional alterations at the single-cell resolution in tissue samples from patients with HGSOC, using single-cell RNA sequencing and T-cell receptor sequencing techniques. Our analyses unveiled notable changes in the tumor signatures after chemotherapy, including those associated with epithelial-mesenchymal transition and cell cycle arrest. Within the immune compartment, we observed alterations in the T-cell profiles, characterized by naïve or pre-exhausted populations following chemotherapy. This phenotypic change was further supported by the examination of adjoining T-cell receptor clonotypes in paired longitudinal samples. These findings underscore the profound impact of chemotherapy on reshaping the tumor landscape and the immune microenvironment. This knowledge may provide clues for the development of future therapeutic strategies to combat treatment resistance in HGSOC.

THE COURSE OF SEPTIC ARTHRITIS FOLLOWING ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION: INFECTIOUS AGENTS, CLINICAL PRESENTATION, AND TREATMENT: A CASE SERIES OF 158 PATIENTS

Septic arthritis following anterior cruciate ligament reconstruction (ACLR) is a rare and serious complication. Previous studies have shown that septic arthritis is associated with inferior outcome of ACLR. Despite that, there is no standardized treatment protocol, and the course of the disease has mainly been studied within single institutions with a small number of patients.The aim of the present study is to describe the course of septic arthritis following ACLR in a large nationwide cohort. The hypothesis was that the clinical presentation of septic arthritis following ACLR varies according to the infectious agent.The present cohort represents patients with septic arthritis identified in a previous study that analyzed compensation claims reported to the Swedish national insurance company (Löf) in 2005–2014 (1). The diagnosis was confirmed by medical experts at Löf after review of medical records. We conducted a comprehensive analysis of the medical records as well as data available from the Swedish National Knee Ligament Registry (SNKLR) for the study group.The study involved 158 patients who received compensation due to developing septic arhtirits. 94 (59.9%) patients were infected with Coagulase negative staphylococci (CoNS), and 25 patients by Staphyolococcus Aureus (S.Aureus) (15.9%). There was a significant difference between the groups regarding Maximum CRP (p&lt;0.001), and duration between ACLR and first washout operation (p&lt;0.005). S.aureus group had the higest maximum CRP (281) and the shortest duration between ACLR and first washout operation (12 days).The Clinical presentation of septic arthritis following ACLR can vary according to the agent causing the infection, and low virulent agents are responsible for the majority of the infections. Clinicians need to be aware of these differences and consider them when making diagnosis or treatment decisions.