Unsuccessful Treatment Research Articles

Recalcitrant Scalp Psoriasis Successfully Treated with Once-Daily Roflumilast Cream 0.3%

Scalp psoriasis is a chronic, immune-mediated skin disease with varying phenotypes and is estimated to affect up to 80% of individuals suffering from psoriasis [1]. The physical symptoms, along with social and emotional impacts of scalp psoriasis can significantly reduce quality of life, necessitating long-term treatment for most patients [3]. Numerous topical and systemic treatments are available for scalp psoriasis, yet the condition remains challenging to manage, underscoring a persistent unmet need for safe and effective therapies [2]. Treatment of the scalp and other hair bearing areas is challenging and can affect the ability to apply topical products and hinder their efficacy [2, 3]. Roflumilast cream 0.3% is a highly selective, non-steroidal and potent topical phosphodiesterase 4 (PDE4) inhibitor approved in 2022 by the FDA for the treatment of psoriasis, including intertriginous disease; in 2023 as a foam for the treatment of seborrheic dermatitis and in 2024, roflumilast cream 0.15% was approved for the treatment of atopic dermatitis. Roflumilast has demonstrated a higher affinity for binding to PDE4 relative to other approved PDE4 inhibitors resulting in greater potency [4, 5]. The results of a phase 3 study investigating roflumilast foam 0.3% in patients with scalp and body psoriasis showed that once daily treatment produced significant clearance of affected areas, rapid improvement in pruritus, and was well-tolerated [6]. Here we report a case involving a 28-year-old female with recalcitrant scalp psoriasis following 10 years of unsuccessful treatment with topical products. Due to the severity of adverse effects experienced with prior therapies, the patient was reluctant to initiate systemic therapy and a trial of once daily topical roflumilast cream 0.3% was initiated. The patient demonstrated rapid improvement after 3 days and clearance of the scalp lesion following daily application for 5 days without any reported adverse effects. Lesions on the patient’s torso also cleared. Upon clearance of lesions, the patient discontinued application of roflumilast cream, and lesions remained clear for several weeks and applies only as needed with any recurrence. Our patient’s case demonstrates the significant potential of roflumilast cream 0.3% in addressing the inflammatory etiology of scalp psoriasis.

Case report: Complications after using the “blind-stitch” method in a dairy cow with a left displaced abomasum: treatment, outcome, and economic evaluation

A fourth lactation dairy cow that was 35 days in milk was referred to the clinic for treatment after undergoing unsuccessful treatment of a left displaced abomasum (LDA). The physical examination revealed complications after using the “blind-stitch” method for correction of the LDA; the cow had an abnormal general demeanor, decreased gastrointestinal motility, and local inflammation of the abdominal wall at the site of the suture. Systemic antibiotics, anti-inflammatory drugs, and intravenous fluids were administered, and a right flank laparotomy and omentopexy according to Dirksen were performed after cutting the suture and breaking down the adhesions of the localized peritonitis between the abdominal wall and the abomasal puncture site. The cow was monitored clinically and discharged 2 weeks after referral. The cow was milked for another two lactations producing a total of 18,000 kg of milk, with a lifetime production of 59,141 kg. The total cost for the case was 310 € for the first intervention using the “blind-stitch” method and 897 € for the second laparotomic intervention. The costs (excluding tax) of both procedures including physical examination, surgery, medications, diagnostics, and labor were calculated. The lost revenue associated with the withdrawal period and lower milk production was 4,168 €. Percutaneous LDA fixation techniques, such as the “blind-stitch” and “toggle-pin” methods, have gained popularity because they are quick and cost-effective and involve minimal labor. However, many buiatricians are critical of these techniques because of the high risk of complications. The following four factors require careful consideration when choosing a method for LDA correction: (1) Percutaneous methods require precision and adherence to the described inclusion, exclusion, and cancelation criteria; (2) Operator skill is essential, and therefore regularly performing laparotomies increases surgical experience and enables the veterinarian to better manage different and more complex abdominal disorders; (3) By performing a laparotomy, other underlying abdominal disorders such as reticuloperitonitis and abomasal ulcers may be detected; (4) Postoperative husbandry and treatment are important factors affecting the outcome. The cost calculated for this case underlines the potential benefit and necessity of successful animal health management and the importance of a highly skilled veterinarian and farm workforce.

Tuberculosis treatment outcome of TB/HIV co-infected patients at Adare Hospital, Hawassa City Administration, Sidama Region.

There is lack of evidence on the TB treatment outcomes of TB/HIV co-infected patients who received anti-TB treatment in Sidama region. In this study, we aimed to assess the treatment outcome of TB/HIV co-infected patients receiving care at Adare Hospital in Hawasa City, Sidama Region. A cross sectional study based on retrospective data among TB/HIV co-infected cases was conducted at Adare Hospital. The unit TB registry and antiretroviral therapy (ART) registry were reviewed for the period between September 1, 2016 and August 31, 2022 to measure TB treatment outcomes. Target population for this study was all TB/HIV co-infected cases aged 15 years or more treated at Adare Hospital in the Hawassa City Administration. The data sources for this study were the unit TB register at the TB clinics, patient charts, and the ART register of the facility. Data were entered and analysed using the statistical package SPSS version 26. A summary descriptive analysis was calculated. Bivariable and multivariable analyses were performed to identify associations between variables. During the study period, 298TB/HIV co-infected cases were treated for TB in the Hospital. Thirty three (11.1%), of the cases had an unfavourable TB treatment outcome. The risk of an unfavourable treatment outcome was over three times higher among re-treated TB cases than among the new TB cases (AOR = 3.3, 95% CI (1.4, 7.9)). The risk of death was higher among stage-IV HIV cases (AOR = 8.1, 95% CI (2.3, 28.9)), and among participants who used non-communicable diseases medications during the cohort period (AOR = 7.3, 95% CI (1.6, 33.6). TB treatment success rate among TB/HIV co-infected cases in the current study was comparable to many other reports. There are factors that contributed for unsuccessful TB treatment outcome. Cautious follow-up of cases and managing these factors could help in improving the TB treatment outcome.

Comprehensive treatment of the patient with venous trophic ulcer

Improving the results of treatment for patients with varicose veins in the lower extremities, complicated by trophic ulcers, is an urgent task for modern medicine. A long-term, recurrent course of the disease leads to a reduction in working capacity and deterioration in quality of life, as well as permanent disability for patients, whose treatment causes special economic problems. At present, there are virtually no effective methods for conservative therapy, leading to prolonged unsuccessful treatment of such patients. This article presents the clinical case of a 63-year-old patient undergoing complex treatment for chronic lower limb venous insufficiency of class C6 according to the CEAP classification. Conclusion. An effective complex method for treating trophic ulcers in patients with chronic venous disease involves the correction of venous hemodynamic disorders (in this case, through radiofrequency ablation), as well as primary surgical treatment for the ulcerative defect, and simultaneous autodermaplasty with a perforated skin flap.

Bone Graft and Fixation Options in the Surgical Management of Scaphoid Nonunion.

Scaphoid nonunions are a complex challenge that are frequently encountered by hand surgeons. Because of the tenuous blood supply of the scaphoid and secondary deformities that occur as a result of delayed or unsuccessful treatment, the treatment of scaphoid nonunions frequently requires the use of internal fixation and supplemental bone graft. There are multiple bone graft sources and techniques that can be employed based on the patient, the viability of the proximal pole fragment, and the presence of a deformity. Without osteonecrosis or disruption of the scaphoid blood supply, nonvascularized autologous grafts can be used from the distal radius, proximal ulna, or iliac crest. In cases where there is concern for an insufficient blood supply, vascularized bone graft sources can be employed, including pedicled local grafts and free flap grafts. When there is a nonviable and fragmented proximal pole, using osteochondral autografts has become increasingly used to reconstruct the scaphoid. Bone graft substitutes can additionally be used to supplement the fixation construct. This review focuses on the indications and role of bone grafts in scaphoid nonunions to help augment internal fixation, promote healing, and restore carpal alignment.

Determinants of unsuccessful tuberculosis treatment outcome in Southwest Ethiopia regional state public hospitals, 2022: a multi-center case control study.

Tuberculosis is the major cause of morbidity, and it is one of the top ten causes of death globally. In Africa, the overall pooled estimate of unsuccessful tuberculosis treatment outcome was reported to be 21.1%, which is above the World Health Organization defined threshold of 15%. Unsuccessful treatment outcomes result in drug resistance, prolonged periods of infection, and increased morbidity and mortality. Therefore, this study aimed to assess determinants of unsuccessful treatment outcomes among tuberculosis patients in Southwest Ethiopia regional state public hospitals, in 2022. A retrospective unmatched case-control study was employed by recruiting 570 study units (190 cases and 380 controls) in three randomly selected public hospitals from 1 August 2022 to 21 August 2022. Data were collected by using a data extraction checklist adapted from tuberculosis registration logbook. Bivariate and multivariate logistic regression models were employed. A predictor variable with a p-value of less than 0.05 in the multivariate logistic regression model was taken as statistically significant. The odds ratio and 95% confidence level were used to measure the strength of the association. A total of 561 records (187 cases and 374 controls) were included from tuberculosis registers. In this study, the factors independently associated with unsuccessful tuberculosis treatment outcome were older age (AOR = 1.68, 95% CI: 1.142, 2.472), rural residence (AOR = 1.548, 95% CI: 1.055, 2.272), retreatment category (AOR = 2.12, 95% CI: 1.339, 3.357), underweight (BMI < 18.5 kg/m2) (AOR = 1.952, 95% CI: 1.240, 3.071), being HIV positive (AOR = 2.144, 95% CI: 1.372, 3.349) and having no treatment adherence support (AOR = 2.016, 95% CI: 1.270, 3.201). In this study, socio-demographic, clinical, and treatment-related factors contributed to the risk of unsuccessful treatment outcomes. Targeted interventions should be taken into consideration to diminish poor tuberculosis treatment outcomes among high-risk groups throughout the whole tuberculosis treatment course.

Role of gastrograffin in adhesive bowel obstruction after unsuccessful conservative treatment: a prospective evaluation

Background: Water soluble gastrograffin (GG) administration via nasogastric (NG) tube has shown to resolve the obstructive features and reduced the need for surgery and reduced hospital stay in the patients presenting with adhesive small bowel obstructions (ASBOs). Thus the use of GG in patients who did not improve after 48 hours of conservative treatment was found to be very useful in the management of ASBOs. Methods: 77 patients presenting with the features of ASBOs in Department of General Surgery, Bir Hospital were included in the study which took place from July 2021 to April 2022. Those patients who presented with the signs of strangulation, peritonitis, complete obstruction and clinical signs of large bowel obstruction were excluded from the study. Results: The mean time at which the symptoms of abdominal pain resolved was 17.45 hours, 28.5 hours and 23.06 hours in patients improved with conservative management, with GG and who undergone surgery respectively. The mean time for passage of flatus was 57.42 hours in patients treated with GG. The mean time in which the patients passed stool was 36.92 hours, 66 hours and 74.8 hours in patients treated with conservative treatment, GG and operated respectively. It took 50.81 hours, 81.68 and 95.4 hours for improvement with conservative management, GG and surgery respectively. Conclusions: The administration of GG in ASBOs after the failure of the initial 48 hours conservative management of ASBOs reduced the need for operative procedures and number of hospital days as most of them did not require surgery.

Is Citation Count a Legitimate Indicator of Scientific Impact? A Case Study of Upper (1974) “The Unsuccessful Self-Treatment of a Case of Writer’s Block” and Its Derivatives

The work by Upper (1974) was a blank paper. Multiple replication studies were published. This work examined the number of citations received by these papers, and manually checked the citing papers to determine why they made the citations. The Dimensions literature database was queried with the search string: (unsuccessful treatment writer’s block). The search yielded 14 articles, two of which were irrelevant and excluded. The 12 papers remained after screening included the original study by Upper (1974), nine replication studies, one review, and one meta-analysis. The original work received 43 citations, but related works had fewer than 10 citations each. One fourth of citations of Upper (1974) were being satiric on “nothing” or “precise” from papers dealing with unrelated concepts, and five citations were deemed erroneous/digressed. One citation was made to acknowledge the reviewer’s comments to Upper (1974), which did not involve Upper’s own ideas. This work exposed a scenario where there were limitations of using citation count as the only metric to gauge scientific impact of journal articles.

Efgartigimod treatment for generalized myasthenia gravis: a single-center case series of 16 patients.

Efgartigimod was approved in Japan in January 2022 for the treatment of generalized myasthenia gravis (gMG), regardless of antibody status. This case series describes a real-world experience in Japan of efgartigimod treatment for gMG patients with diverse backgrounds. We retrospectively analyzed the medical records of 16 Japanese patients (11 females and five males, mean age 40.4 years) with gMG who received efgartigimod at the Kumamoto University Hospital between August 2022 and September 2023. The outcomes were Quantitative Myasthenia Gravis (QMG) responders (≥ 3 point reduction), IgG levels, and change in prednisolone dose, in the first cycle of efgartigimod. Fifteen patients completed one cycle of efgartigimod. Of the 14 patients for whom QMG scores were obtained, 10 patients were QMG responders. Four of the five patients with Myasthenia Gravis Foundation of America class V were QMG responders. Improvement in QMG after efgartigimod treatment was observed in one patient with myasthenic crisis and in one refractory patient who had unsuccessful eculizumab treatment. The mean reductions from baseline in IgG levels at weeks 1, 2, 3, and follow-up were 38.3, 56.1, 63.1, and 43.9%, respectively. A decrease in prednisolone dose was observed in seven patients. The most common adverse events were headache (three patients) and diarrhea (two patients). One patient discontinued efgartigimod treatment due to a treatment-related adverse event of rash. Improvements in the outcomes of patients with gMG, including patients with severe gMG, myasthenic crisis, and refractory to anti-complementary therapy, were observed after the first cycle of efgartigimod treatment. Our real-world experience in Japan suggests the future possibilities for the treatment with efgartigimod for gMG with diverse backgrounds.

Childhood tuberculosis outcomes and factors associated with unsuccessful treatment outcomes in selected public hospitals of Lusaka Zambia from 2015 to 2019.

Treatment outcomes of tuberculosis in children are rarely evaluated. Childhood tuberculosis has been a low priority for tuberculosis programs due to difficulties in diagnosis and treatment. This study evaluated childhood tuberculosis outcomes and factors associated with unsuccessful treatment outcomes in selected public hospitals in Lusaka, Zambia from 2015 to 2019. This was a cross-sectional study conducted in eight public hospitals in Lusaka. All children aged 0-14 years, treated with tuberculosis and had treatment outcomes evaluated were included. The WHO tuberculosis treatment outcomes were grouped into successful treatment outcome (cured, treatment completed) and unsuccessful treatment outcome (death, loss to follow-up, failure). Taking unsuccessful treatment outcome as the outcome variable, logistic regression models were performed. All analyses were done at a 95% confidence interval. Out of 2,531 children managed for TB from 2015 to 2019, only 1,495 (59.1%) had treatment outcomes evaluated. Out of 1,495 participants, majority were 5 to 14 years old (50.9%), males (51.1%), HIV-negative (58.7%), and had pulmonary tuberculosis (74.2%). Bacteriological tests were performed on 59.8% of children, where 21.6% had positive bacteriological results. Bacteriologically confirmed TB was higher in children over 5 years (29.5%), pulmonary TB (25.6%), and retreatment (28.6%). The majority of children (84.2%) completed treatment, while 10.7% were cured, 1.5% were lost to follow-up, 3.1% died, and 0.5% failed treatment. Overall, unsuccessful treatment outcome was 5.1% while successful treatment outcome was 94.1%. Extrapulmonary tuberculosis was associated with unsuccessful treatment outcomes (AOR 1.64; 95% CI: 1.02-2.62). The tuberculosis successful treatment outcome met the World Health Organization's threshold goal of 90%. Children with extrapulmonary tuberculosis should be targeted as a high-risk group to improve treatment outcomes. Tracking children whose treatment outcomes were not evaluated would provide more precise estimates of TB treatment outcomes.

Umbilical Cord Blood Platelet Lysate Eyedrops for the Treatment of Severe Ocular Surface Disorders in Graft vs. Host Disease Patients: Clinical Study

Background: Graft-versus-host disease (GvHD) is an overactive systemic inflammatory response that can arise following allogeneic hematopoietic stem cell transplantation (HSCT). This condition occurs when the transplanted donor immune cells recognize the recipient’s tissues as foreign and trigger an immune response against them. The ocular surface (eyelids, conjunctiva, meibomian glands, lacrimal glands, and cornea) is particularly involved in GvHD, and its response to existing treatments, including potent immunosuppressants and new targeted therapies, is undesirable, with such treatments often being ineffective. Human allogeneic umbilical cord blood platelet lysate stands out as a potent adjunct to conventional therapies for ocular surface disorders related to severe Dry Eye Disease. This study aimed to evaluate the safety and efficacy of umbilical cord blood platelet lysate eyedrops for the treatment of severe ocular surface disorders in graft-versus-host disease patients who have received previous unsuccessful treatments. Methods: This study was a prospective, non-comparative, interventional case series study involving 22 patients (10 females and 12 males) aged 25–46 years with severe ocular surface disorders that were unresponsive to standard treatments. The GvHD patients were categorized based on the severity of their ocular surface disorders into three groups: Group I: five patients with severe Dry Eye Disease and filamentary keratitis; Group II: eight patients suffering from severe blepharo-kerato-epitheliopathy; Group III: nine patients with corneal ulcers. Fresh umbilical cord blood (UCB) was obtained from healthy donors and subjected to centrifugation using a novel PRP preparation kit provided by Sciacca (AG) Cord blood bank, Italy in a one-step process. In all groups, the outcomes before and after treatment were evaluated by means of the OSDI (Ocular Surface Disease Index), SANDE (Symptom Assessment in Dry Eye) questionnaire, VAS (Visual Analogue Scale), slit lamp examination, Esthesiometry, Lissamine Green Staining, the NIBUT (Non-Invasive Break-Up Time) and BUT, fluorescein staining with digital photography and Oxford classification, the Schirmer Test, the Best Corrected Visual Acuity (BCVA), and Meibography. In Group III at each evaluation time, the size of the ulcer and its relative reduction compared to the baseline size were recorded. Clinical variables, such as corneal inflammation, conjunctivalization, corneal neovascularization, or pain, were also considered individually. Results: We observed a significant improvement in the SANDE, VAS, and OSDI scores; Schirmer Test; BUT; BCVA; and Oxford classification after treatment with allogeneic cord blood serum eyedrops. Nevertheless, pain and inflammation reduced markedly over time until complete healing in all cases. The mean reduction in the ulcer surface area (compared to baseline values) was significantly higher at all assessment points (p = 0.001 for day 7 and p &lt; 0.001 for subsequent time points every 30 days for 90 days). At the last check-up (after 90 days of treatment), the number of ulcers (Group III, nine patients) with a reduction in size of greater than 50% was eight (88.8%), of which seven ulcers were completely healed. None of the patients experienced treatment-related local or systemic adverse events. In this study, using a relatively large number of cases, we demonstrated that the use of umbilical cord blood platelet lysate eyedrops is a safe, feasible, and effective curative approach for severe ocular surface disease in patients with GvHD. Conclusions: Our pilot study highlights the remarkable effectiveness of allogeneic cord blood serum eyedrops in patients with severe ocular surface disorders following GvHD who have shown an inadequate response to the usual treatments. It is mandatory to design future studies on the efficacy of this therapeutic approach for acute ocular, mucosal, and cutaneous GvHD.

Multifunctional poloxamer-based thermo-responsive hydrogel loaded with human lactoferricin niosomes: In vitro study on anti-bacterial activity, accelerate wound healing, and anti-inflammation

Chronic wound infections are attributed to delayed tissue repair, which remains a major clinical challenge in long-term health care. Particularly, infections with antibiotic resistance have more serious effects on health, often resulting in unsuccessful treatments. Thus, antimicrobial peptide (AMP)-based therapy holds promise as a potential therapeutic approach to overcoming drug resistance. Conventional wound dressing is a passive strategy for wound care that is not capable of eradicating pathogens and promoting tissue repair. In this study, we aim to construct an advanced wound dressing; a thermo-responsive hydrogel incorporated with lactoferricin (Lfcin) niosome (Lfcin-Nio/hydrogel) for bacterial pathogen treatment. The Lfcin-loaded niosome (Lfcin-Nio) has a particle size of 396.91 ± 20.96 nm, 0.38 ± 0.01 of PdI, −10.5 ± 0.3 mV of ζ potential, and 72.30 ± 7.05 % Lfcin entrapment efficiency. Lfcin-Nio exhibited broad antibacterial activity on both drug-susceptible and drug-resistant strains, and also on bacteria residing in the biofilm matrix. The Lfcin-Nio/hydrogel was fabricated from 0.5 % w/v poloxamer 188–20 % w/v poloxamer 407, and supplemented with Lfcin-Nio and epidermal growth factor (EGF). The physical properties of Lfcin-Nio/hydrogels showed elasticity, swelling ability, and strong injectability with responsiveness to 33–37 °C temperatures. The biological properties of Lfcin-Nio/hydrogels exhibited a bactericidal effect against drug-resistant strains of S. aureus and P. aeruginosa, and showed less toxicity to the human skin fibroblast. It also promoted the healing of scratches by 55 % within 6 h, compared to the wound closure rate of 20 % in the cell control. The inflammatory response of the Lfcin-Nio/hydrogel-treated cells was reduced via suppression of IL-1β and COX-2 mRNA expressions. From this study, Lfcin-Nio/hydrogels can be suggested as a modern wound dressing that possesses multifunctional and beneficial properties for the management of chronic wound infections.

Endovascular Management of Thrombosed Cavoportal Anastomosis After Liver Transplantation Using Catheter Directed Thrombolysis and Stent Placement: A Case Report

Cavoportal hemitransposition (CPHT) is a rarely performed treatment technique in liver transplantation in cases of extensive splanchnic thrombosis, in which the inferior vena cava of the recipient is used to perfuse the portal vein of the allograft. A case of a 65-year-old liver transplantation patient with an acutely thrombosed cavoportal anastomosis is presented. After unsuccessful medical treatment, recanalization was obtained with transfemoral catheter directed thrombolysis, angioplasty and stent placement. Although this type of treatment has been extensively documented for the management of portal anastomotic problems after orthotopic liver transplantation, data on its application in modified transplantation techniques including CPHT are rare. This technique provides a minimally invasive treatment option in CPHT patients with cavoportal anastomotic problems, who might otherwise require complex surgical repair or retransplantation.

Beyond bedwetting: How successful treatment is observed in sleep macrostructure

IntroductionSleep enuresis (SE), commonly known as bedwetting, refers to involuntary urination during sleep. It is a prevalent condition affecting approximately 15 % of children at age 5, 10 % by age 7, and 5 % by age 10. This condition can significantly impact both children and their families. The pathophysiology of SE is complex and not yet fully understood. There are several established treatment methods, but limited information on their sleep dynamics. ObjectiveThis study aimed to evaluate differences in sleep structure before and after treatment in patients with monosymptomatic SE (MSE), focusing on alarm therapy, desmopressin, and a combination of both. The analysis compared pre- and post-treatment differences within each treatment arm. The analysis was conducted for both successful and unsuccessful treatment outcomes. Methods/resultsThis was a prospective study with MSE patients, aged 6–16 years, diagnosed by multidisciplinary assessment. Of the 140 initial applicants 75 were initially included in the study and randomized for therapeutic intervention in three treatment arms, namely: alarm, desmopressin and alarm + desmopressin. Therapeutic response was evaluated 12 months after treatment discontinuation. Polysomnographic evaluation pre and post treatment was carried out. 51/75 completed the entire protocol. 42/51 were successfully treated and had a median age of 10 [8–12] and the non-success, 8 [7–10]. Among the successful patients, the percentage of N2 sleep decreased from a median of 55.7 %–48.5 % (p = 0.0004) in the alarm arm, from 58.8 % to 50 % (p = 0.002) in the desmopressin arm, and from 54.7 % to 50.9 % (p = 0.044) in the combined arm. The percentage of N3 sleep increased from 25.7 % to 30.1 % (p = 0.004) in the alarm arm, from 21.6 % to 26 % (p = 0.032) in the desmopressin arm, and from 23.7 % to 28.3 % (p = 0.014) in the combined arm. The arousal index significantly increased from pre-to post-treatment in all arms: in the alarm arm, from 1.25 to 2.8 (p = 0.002); in the desmopressin arm, from 1.3 to 2.7 (p = 0.019); and in the combined treatment arm, from 1 to 4 (p = 0.003). No significant differences were observed in the non-successful arm or among those who experienced complete resolution of the enuresis without treatment. ConclusionThe observed increase in N3 sleep and arousal and decrease in N2 sleep following successful treatment, regardless of the specific interventions, underscores the role of sleep in the pathophysiology of enuresis. Conversely, the lack of sleep differences in the non-successful arm further highlights the importance of sleep, beyond developmental factors, in influencing the clinical outcomes of enuresis, especially since all children were assessed 12 months after the start of treatment.

12. Vascular pain: Ischemic pain in the extremities and Raynaud's syndrome

Peripheral artery diseases (PAD) and Raynaud's syndrome are associated with substantial morbidity. PAD, through the restriction of blood flow to the extremities, may lead to critical limb ischemia with symptoms of pain at rest which may eventually progress to severe limb ischemia with gangrene. This serious and painful clinical condition requires extensive medical care, is limb-threatening and, in case of delayed or unsuccessful treatment, is associated with a high mortality rate. In Raynaud's syndrome, the blood supply to certain parts of the body, usually the fingers and toes and less frequently the nose or ears, is restricted because of vasculopathy of the smaller vessels at acral sites. Under certain circumstances, with cold as the most well-known provoking factor, blood flow restriction occurs, leading to demarcated color changes and symptoms such as pain, paresthesia, and numbness. In severe cases of Raynaud syndrome tissue ischemia may lead to necrosis and the need for amputation of the affected area. In this narrative review, the literature on the diagnosis and interventional pain treatment of PAD and Raynaud's syndrome was updated and summarized. This review focused on interventional pain treatment. In PAD, the effects of the intervention on limb salvage, ulcer healing, and ischemic pain were summarized. Additionally, results with respect to skin microcirculation and quality of life were reported if available. In Raynaud's syndrome, we focused on the effect of the intervention on peripheral blood flow metrics and pain intensity during attacks. In PAD, prevention and treatment of risk factors are important. Initially, conservative treatment and pharmacological therapy are preferred first-line therapies. However, when disease progression occurs, interventional management may be considered. The literature search yielded conflicting evidence for sympathectomy as a treatment for PAD. Spinal cord stimulation (SCS) as a treatment modality for advanced PAD had high-quality evidence for limb salvage in subgroups of patients but conflicting evidence for other outcome measures such as pain, wound healing, and quality of life. The literature search for interventional pain management in Raynaud's syndrome was limited to only one randomized controlled trial (RCT) studying the effect of thoracic sympathectomy. This study had several limitations and hence the level of evidence for this interventional treatment is very low. No RCTs studying SCS in patients with Raynaud's syndrome were found. In both PAD and Raynaud's syndrome, additional RCTs are needed to substantiate interventional (pain) management and bolster the evidence base for sympathectomy and SCS as treatment options.

Predictors of appendicectomy one year after antibiotic treatment for acute appendicitis: Insights from a prospective, multicentre, observational study.

Surgeons are sometimes reluctant to manage uncomplicated appendicitis non-operatively. Reasons cited include the risk of recurrent appendicitis and the risk of missed appendiceal malignancy. The aim of this study was to address these uncertainties and determine the long-term efficacy of antibiotic versus operative management of appendicitis. One-year follow-up of patients enrolled in the multicentre, COVID:HAREM cohort study during March-June 2020 was performed. Initial operative or non-operative management was determined on a case-by-case basis by the responsible surgeon. Outcomes were appendicectomy rate at 1-year, histology of removed appendix and predictors of unsuccessful antibiotic treatment. A total of 625 patients who had non-operative management were included. Emergency appendicectomy had been performed by 1-year in 24% (149/625), with a median time to appendicectomy of 12days [IQR 1-77] from presentation. Thirty-one patients had elective appendicectomy. Normal histology was reported in 6% of emergency procedures and 58% of elective ones. There were 7 malignancies and 3 neuroendocrine tumors identified at histology. All patients with malignant histology had ≥1 risk factors for malignancy at initial presentation. Faecolithiasis (hazard ratios (HR) 2.3, 95% confidence intervals (CI) 1.51-3.49) and a high Adult Appendicitis Score (AAS >16; HR 2.44, 95% CI 1.52-3.92) were independent risk factors for unsuccessful non-operative management. At 1year, 71% of patients managed non-operatively did not undergo an appendicectomy. Recurrence of appendicitis was associated with faecolithiasis and a high AAS. Patients at higher risk for appendiceal malignancy should have targeted follow-up. These factors should be considered when counseling patients on non-operative management.

A Rare Case of Meningitis Caused by Elizabethkingia meningoseptica in a Baby at the Buea Regional Hospital, South West Region, Cameroon

Aim: This report was aimed at determining the possible source, risk factors, antimicrobial susceptibility pattern and clinical management of the first recorded case of meningitis in Cameroon caused by Elizabethkingia meningoseptica. Presentation of case: A 10 months old baby previously diagnosed with otitis media was admitted at the Buea regional hospital on the 21st of October 2023 after a referral following unsuccessful treatment. Upon admission, the baby had persistent fever, catarrh (evidence of an upper respiratory tract infection) and abdominal discomfort. Patient developed decreased body movement, altered consciousness and neck stiffness even after being placed on ampicillin and cefotaxime for two days. Based on cerebrospinal fluid analysis, the patient was considered a probable meningitis case and put on ceftriaxone to no avail. CSF culture later revealed the presence of Elizabethkingia meningoseptica susceptible to ciprofloxacin and resistant to imipenem, amoxicillin-clavulanic acid, cotrimoxazole, ampicillin and ceftriaxone. Marked improvement was noticed and the patient was discharged following full recovery after treatment with ciprofloxacin for 21 days. Epidemiological investigations and active case search did not provide any evidence of the Elizabethkingia being acquired in the hospital. Discussion and conclusion: The Elizabethkingia in this case was most likely community acquired associated with acute otitis media probably linked to a recent upper respiratory tract infection. The isolate was resistant to ceftriaxone and susceptible to ciprofloxacin. In case of meningitis caused by this pathogen, empirical treatment with fluoroquinolones may most likely be an effective option in the absence of antimicrobial susceptibility testing.

An integrated framework for the study of exercise across the postdiagnosis cancer continuum.

Exercise plays many important roles across the entire cancer continuum that have been described in previous frameworks. These frameworks, however, have generally provided a simplified description of the roles of exercise postdiagnosis. The modern cancer treatment landscape has become complex and often consists of multiple lines of multimodal treatments combined concurrently and/or sequentially and delivered over many months or years. This complexity requires a more multifaceted and targeted approach to the study of exercise after a cancer diagnosis. Here, we propose a new integrated framework-Exercise Across the Postdiagnosis Cancer Continuum (EPiCC)-that highlights the distinct roles of exercise for disease treatment and supportive care from diagnosis until death. We also propose new terminology to clarify the distinct roles of exercise that emerge in the context of the modern cancer treatment landscape. The EPiCC Framework is structured around multiple sequential cancer treatments that highlight six distinct cancer treatment-related time periods for exercise-before treatments, during treatments, between treatments, immediately after successful treatments, during longer term survivorship after successful treatments, and during end of life after unsuccessful treatments. The EPiCC Framework proposes that the specific roles of exercise as a disease treatment and supportive care intervention will vary depending on its positioning within different cancer treatment combinations. As a cancer treatment, exercise may serve as a "priming therapy", primary therapy, neoadjuvant therapy, induction therapy, "bridging therapy", adjuvant therapy, consolidation therapy, maintenance therapy, and/or salvage therapy. As a supportive care intervention, exercise may serve as prehabilitation, intrahabilitation, interhabilitation, rehabilitation, "perihabilitation", health promotion/disease prevention, and/or palliation. To date, exercise has been studied during all of the cancer treatment-related time periods but only in relation to some cancer treatments and combinations. Moreover, fewer studies have examined exercise across multiple cancer treatment-related time periods within any cancer treatment combination. Future research is needed to study exercise as a disease treatment and supportive care intervention within and across the distinct cancer treatment-related time periods contained within different cancer treatment combinations. The aim of the EPiCC Framework is to stimulate a more targeted, integrated, and clinically-informed approach to the study of exercise after a cancer diagnosis.

Successful treatment of pyoderma gangrenosum with guselkumab

AbstractGuselkumab, a monoclonal antibody known for its effective inhibition of T‐cell‐immunoactivity through specific binding to interleukin‐23 (IL‐23)‐cytokines, may be used for off‐label treatment of pyoderma gangrenosum (PG). Herein, we report two successful cases of off‐label treatment for PG, using guselkumab, after unsuccessful treatments with standard regimens of corticosteroids, immunomodulating therapy and other biological agents. Case 1 involves a 39‐year‐old female with treatment‐resistant peristomal PG post‐colectomy and ileostomy. Case 2 features a 35‐year‐oldfemale with treatment‐resistant PG, presenting with deep necrotic lower extremity ulcers. In both cases, we observed remarkable healing within months to a year. These two cases support the potential use of systemic IL‐23‐targetedtherapy for treatment‐resistant PG.

Assisted oocyte activation significantly improves zygote formation, cleavage, and implantation rates in patients with a history of fertilization failures.

Fertilization check performed at the 18th hour following classic in vitro fertilization procedure (IVF) or intracytoplasmic sperm injection (ICSI) is a critical stage in assisted reproduction. The success of the treatment is significantly reliant on the quantity of zygotes exhibiting two pronuclei. Consequently, low fertilization rates or complete fertilization failure are highly undesirable outcomes for both patients and reproductive specialists. Applying additional calcium ionophore for oocyte activation subsequent to ICSI may offer benefits and potentially enhance treatment outcomes, particularly for patients who have experienced low or absent fertilization rates (FR) in previous treatment cycles. The aim of the study is to evaluate the efficacy of Ca2+ ionophore application for oocyte activation. A retrospective analysis of 924 oocytes obtained from 120 patients who underwent ICSI cycles with a history of low or no fertilization as a result of previous unsuccessful treatment rounds. The next ART cycle followed with additional oocyte Ca2+ ionophore activation applied in 57 of the cases in order to optimize the treatment process (Group 1), and 63 patients were included and their outcomes followed as a control group (Group 2).We conducted a comparative analysis of results in both groups. The study's primary outcomes encompassed fertilization, cleavage embryo quality, blastocyst rate, and established clinical pregnancies. At day 1fertilization check we had 274/386 zygotes (71%FR) in group 1 and 132/410 in group 2 (32.2%FR), (P<0.0001). Twenty-two (34.9%) cycles in group 2 resulted in total fertilization failure (TFF). At the cleavage stage top-quality embryos from group 1 were significantly higher (P = 0.0021) in comparison to group 2. Forty-eight embryo transfers (ET) were performed in group 1 resulting in 41.67% clinical pregnancies versus 33 ET and only 4 pregnancies (12.12%) for group 2 (P = 0.0044). The results confirm the appropriateness of assisted oocyte activation as an additional method in cases of previous fertilization failure cycles.