Published Case Reports Research Articles

Apremilast for the Treatment of Psoriasis in Special Areas in Pediatric Patients in the SPROUT Study

Introduction & Objective: Psoriasis in special areas is difficult to treat and causes significant disease burden. Approved systemic therapies for moderate to severe plaque psoriasis in pediatric patients are limited and require subcutaneous injection. Apremilast, a unique oral immunomodulator that inhibits phosphodiesterase-4, is approved in multiple countries for use in adults with psoriasis, regardless of severity. In this study, the efficacy of apremilast for psoriasis in special areas in pediatric patients was assessed over 16 weeks.  Materials & Methods: SPROUT (NCT03701763) is a phase 3, randomized, double-blind, placebo-controlled study in patients 6-17 years with moderate to severe plaque psoriasis (Psoriasis Area and Severity Index ≥12, body surface area ≥10%, and static Physician Global Assessment [sPGA] ≥3) inadequately controlled by/inappropriate for topical therapy. Patients were stratified by age and randomized 2:1 to receive apremilast (weight-based 20 mg or 30 mg twice-a-day) or placebo for 16 weeks, then apremilast through week 52. Scalp Physician Global Assessment (ScPGA) response, modified sPGA of genitalia (sPGA-G) response, Whole Body Itch-Numeric Rating Scale (WBI-NRS) response, and change from baseline in Children’s Dermatology Life Quality Index (CDLQI) were assessed through week 16.   Results: Of 245 randomized patients (apremilast: 163; placebo: 82), 101 (41.2%) were 6-11 years and 144 (58.8%) were 12-17 years; 120 (49.0%) patients weighed ≥20 to <50 kg and 125 (51.0%) weighed ≥50 kg. At baseline, 81.0% of the patients treated with apremilast and 84.1% of patients treated with placebo had moderate to severe scalp psoriasis (ScPGA ≥3). Significantly more patients achieved ScPGA response at week 16 with apremilast vs placebo (36.4% vs 18.8%; P=0.0091). At baseline, 110 patients (44.9%; 45.4% apremilast and 43.9% placebo) had moderate to severe genital psoriasis (sPGA-G ≥3). Achievement of sPGA-G response at week 16 was numerically greater with apremilast vs placebo (39.2% vs 25.0%), although not significant, possibly due to small sample size (apremilast: n=74; placebo: n=36). Significantly more patients achieved WBI-NRS response at week 16 with apremilast vs placebo (52.0% vs 32.1%; P=0.0110). Greater improvements in CDLQI were seen at week 16 with apremilast vs placebo (least-squares mean change from baseline −5.1 vs −3.2; P=0.0009). Adverse events were consistent with the known apremilast safety profile. In 21 patients vaccinated during the study (including for COVID-19, influenza, diphtheria, pertussis, tetanus, meningococcus, and hepatitis B), no new safety issues occurred.   Conclusions: Apremilast significantly improved scalp psoriasis, itch, and quality of life in pediatric patients with moderate to severe psoriasis. At week 16, patients with moderate to severe genital psoriasis showed a trend toward improvement, although not significant due partially to the sample size.  

Trends in female authorship in Acta Anaesthesiologica Belgica from 2005 to 2021

Purpose: This study aims to investigate the trend of female representation in publishing in the Acta Anaesthesiologica Belgica (AAB) from 2005 to 2021. In recent years, there has been an increased focus on gender equality and disparity. However, as far as we know, an evaluation of the Belgian literature in this regard has not been undertaken before. Methods: The study’s main objective is on determining the gender of the first author, with the gender of the second and last authorship position being secondary outcomes. Additionally, the study aimed to investigate whether other variables, such as the field in which the article was published, study type, the country of origin (of the first author), the first author’s academic degree, the number of authors, and coauthors’ gender, are related to these outcomes. Results: In total 475 manuscripts were included for data collection, of which 146 (30.7%) had a female first author, 94 (19.8%) had a female second author, and 61 (12.8%) had a female last authorship position. We demonstrated a trend towards greater gender equality in the AAB over time, with more women occupying first and second authorship positions. However, we observed a stagnation in female last authorship positions, with only a small increase of last female authorship of 1.16% reaching 7.41% in 2021. Further analysis showed that female last authorship affected first female authorship. As the number of authors increases, the representation of women (particularly for the last author) diminishes compared to their male colleagues. Lastly, the analysis of gender in relation to the number of coauthors showed that male authors are more likely to publish alone (as a single author) compared to their female colleagues. The AAB predominantly published case reports, observational studies, and narrative reviews, all of which had a higher number of male authors than female authors. The study also uncovered the absence of female first authors in the four systematic reviews published. Conclusion: From 2005 to 2021, the number of female first authors in the AAB has increased, and there has been a small but steady rise in female last authorship position. However, articles published in the AAB still exhibit a lower representation of female first authors. It is crucial to conduct further research and raise attention to gender disparity in anesthetic – and per extension in scientific - literature.

Kidney cancer metastases to breast and other genitourinary (GU) organs: A pooled analysis.

401 Background: As the number of kidney cancer survivors increases, the appearance of second malignancies and unusual metastatic patterns is increasing. We performed a pooled analysis to assess the clinicopathologic findings, treatment, and outcomes of cases involving breast and GU organs. Methods: Pooled analysis of published case reports and case series of renal cell carcinoma (RCC) metastasis to breast and genitourinary (GU) organs, including four cases from our institution. Parameters were compared between GU organ cohorts using a one-way ANOVA test and subgroup analysis. Results: 127 patients with GU metastasis of RCC were analyzed. The overall mean age was 61.2 years (Range: 14-92). GU organs with reported metastasis included 24 to testis (18.9%), 18 to penis (14.2%), 18 to breast (14.2%), 17 to vagina (13.4%), 17 to bladder (13.4%), 14 to ovary (11%), 7 to prostate (5.5%), and 6 to urethra (4.7%). Median Fuhrman grade was 2.5 overall, with penis metastases (n=4) having a median grade of 4. 95 of 111 (86%) cases reported patients with GU metastasis that had a prior nephrectomy for RCC. Patients with breast metastasis (n=16) had a significantly longer time between nephrectomy and metastatic diagnosis (90.1±63.1 months) than penile (12.7±16.1 months, n=6, p<0.01), bladder (28.7±26.6 months, n=15, p<0.01), or vaginal cohorts (6.7±5.2 months, n=3, p<0.05). Co-metastasis to extra-GU sites were most prevalent in penile metastasis (47.4%, n=9). The primary treatments for metastases were excisional surgery (79%), immunotherapy (18%), radiotherapy (14%), and tyrosine kinase inhibitors (13%). The breast cohort (n=10) reported a 90% survival rate at final follow-up, while the vaginal (n=8) and penile (n=12) cohorts reported survival rates of 50%. The urethra cohort (n=2) had a median survival time of 53 months, while the breast cohort (n=10) had a median survival time of 6 months. Conclusions: While kidney cancer's metastasis to other GU organs is relatively uncommon, it presents unique diagnostic and therapeutic challenges. Recognizing these patterns and understanding the biology behind such spread can offer insights into RCC's behavior and drive more effective treatments. [Table: see text]

The spectrum of psychiatric manifestations in subacute sclerosing panencephalitis: A systematic review of published case reports and case series.

Data related to psychiatric manifestations in subacute sclerosing panencephalitis (SSPE) is currently available only in the form of isolated case reports. In this systematic review, we evaluated the spectrum of psychiatric manifestations and their impact on the course and outcome of SSPE. Data were obtained from 4 databases (PubMed, Embase, Scopus, and Google Scholar), with the most recent search conducted on March 27, 2023. The PRISMA guidelines were followed, and the PROSPERO registration number for the protocol is CRD42023408227. SSPE was diagnosed using Dyken's criteria. Extracted data were recorded in an Excel spreadsheet. To evaluate the quality of the data, the Joanna Briggs Institute Critical Appraisal tool was employed. Our search resulted in 30 published reports of 32 patients. The mean age was 17.9 years. Schizophrenia, catatonia, and poorly characterized psychotic illnesses were the 3 most common psychiatric presentations that were seen in 63% (20/32) of cases. Catatonia was seen in 4 patients. Affective disorders, mania, and depression were reported among 22% (7/32) cases. In approximately 81% (26/32) cases, the course of SSPE was acute fulminant. Treatment with antipsychotic drugs had poor or no response. Out of 17 patients, who received antipsychotic drugs, 6 patients noted severe extrapyramidal adverse effects. SSPE often masquerades as a psychiatric disorder. Unresponsive psychiatric symptoms, early extrapyramidal signs, and progressive encephalopathy indicate SSPE.

Homoeopathy – An Alternative to Conventional Treatment for Infertility

AbstractInfertility is a disease of reproductive system in males or females. It is defined as inability to achieve pregnancy after 12 months or more of unprotected sexual intercourse. As per the World Health Organisation, the availability, access and quality of infertility treatment are challenges in most countries especially the middle- and low-income countries. Infertility has a negative psychological and social impact for couples. The cost of conventional treatment which includes medicines and assisted reproductive techniques can be a deterrent for many. Published case reports have shown positive pregnancy outcome in infertility cases treated with homoeopathy due to both male and female causes. There is a need to make homoeopathic treatment for infertility accessible to general population through focused outpatient departments (OPDs) and also consolidate research-based evidence of efficacy of homoeopathy in infertility through well-designed comparative randomised controlled trials (RCTs). Towards this, Dr. D. P. Rastogi Central Research Institute of Homoeopathy has made effort to start weekly infertility OPD. The institute is also in process of initiating a RCT on female infertility in polycystic ovary syndrome cases with comparative arm of conventional treatment and homoeopathic treatment.

Topical Clindamycin For Acne Vulgaris: Pharmacovigilance Safety Review and Retrospective Analysis of Gastrointestinal Events

Background: Clindamycin, a lincosamide antibiotic, was the 125th most prescribed medicine in the US in 2020. Topical formulations that combine clindamycin with benzoyl peroxide or a retinoid are commonly used for acne vulgaris (AV) treatment. While oral and topical clindamycin carry warnings/contraindications regarding the development of gastrointestinal (GI) adverse events (AEs), the real-world incidence of these AEs with topical clindamycin is unknown. The objective is to provide an overview of safety data for topical clindamycin when used for AV treatment.
 Methods: Safety data from published literature on PubMed® (case reports, clinical trials data, retrospective data), previously unpublished worldwide pharmacovigilance data (from January 1, 1900-December 31, 2022), and two unpublished retrospective cohort studies of US electronic medical records (EMR; January 1, 2011 to January 31, 2019) were reviewed, with a focus on inflammatory bowel disease (IBD) and GI AEs following topical clindamycin monotherapy or combination treatment
 Results: There have been only 4 published case reports of topical clindamycin-associated GI AEs, which were all published between the years 1981-1997. In 8 published pivotal phase 3 clinical trials of topical clindamycin monotherapy or combination treatment for AV, GI-related AEs were reported in 1.4% of clindamycin-treated participants (38/2,672; safety populations). According to the pharmacovigilance data, the rate of GI-related adverse drug reactions with topical clindamycin-containing products was 0.000045% (64/141,084,533). In 1 published retrospective report, there were 0 reports of colitis from the 1,124 patients estimated to have received topical clindamycin prescriptions in the years 1977-1980. In the first retrospective EMR study, results indicate that physicians prescribe topical clindamycin for AV treatment equally to patients with a history of IBD (19.0%; 98/515) or without (20.7%; 14,495/70,151). The second retrospective EMR study showed that among patients with AV and an initial prescription for topical clindamycin (monotherapy or combination; n=18,012), there were 3 (0.02%) incident cases of pseudomembranous colitis within 30 days; none of these cases had a history of IBD.
 Conclusions: A review of published case reports, clinical trials safety data, worldwide pharmacovigilance data, and retrospective US prescription data demonstrate that GI events—including colitis or pseudomembranous colitis—in patients exposed to topical clindamycin is extremely low, regardless of IBD history.
 Support: Ortho Dermatologics

Talon Cusp from Southern Region of Saudi Arabia: Report of Two Cases with Mini Review

Talon cusp is an uncommon dental anomaly characterized by the presence of an accessory cusp-like structure projecting from the cingulum area of an anterior teeth. This anomaly generally poses problems for the patient in terms of esthetics, caries control and occlusal accommodation. This cases report with mini-review presents a brief classification of talon cusp, summary of published case report worldwide, and a unique occurrence of maxillary talon cusp in a 23-year female and 9-year male patient. The clinical and radiographic findings, along with the management of this rare dental anomaly are discussed.

Melanoma of the central nervous system based on neurocutaneous melanocytosis in childhood: A rare but fatal condition.

Melanomas of the central nervous system (CNS) based on neurocutaneous melanocytosis (NCM) are exceptionally rare in childhood and have been described only sporadically. Rapidly progressive disease may represent a major challenge for treating physicians, especially given the limited knowledge about this condition. This analysis aimed to increase knowledge about the occurrence and treatment of these malignancies. Data on diagnosis, treatment, and outcome of patients aged 0-18 years with CNS melanoma based on NCM recorded in the German Registry for Rare Pediatric Tumors (STEP registry) were analyzed. Additionally, published case reports on this condition were analyzed. In STEP, five patients with leptomeningeal melanoma based on NCM were identified, with a median age at melanoma diagnosis of 3.7 years. Various multimodal treatments were performed: (partial) resection (n=4), irradiation (n=2), trametinib (n=3), different cytostatics (n=2), and anti-GD2 immunotherapy (n=1). All patients died between 0.3 and 0.8 years after diagnosis. Including published case reports, 27 patients were identified with a median age of 2.8 years at melanoma diagnosis (range: 0.2-16.6). Fourteen of 16 cases with reported data had a NRAS alteration (88%), particularly NRAS p.Q61K (85%). In the expanded cohort, no patient survived longer than 1 year after diagnosis despite multimodal therapy (including trametinib; n=9), with a median survival of 0.4 years (range 0.1-0.9). CNS melanomas based on NCM in childhood are aggressive malignancies without curative treatment to date. Therapeutic approaches must be individualized. Genetic tumor sequencing is essential to improve understanding of tumorigenesis and potentially identify new therapeutic targets.

Clinicopathological differences between Bartonella and other bacterial endocarditis-related glomerulonephritis - our experience and a pooled analysis.

Although Staphylococcus aureus is the leading cause of acute infective endocarditis (IE) in adults, Bartonella spp. has concomitantly emerged as the leading cause of "blood culture-negative IE" (BCNE). Pre-disposing factors, clinical presentation and kidney biopsy findings in Bartonella IE-associated glomerulonephritis (GN) show subtle differences and some unique features relative to other bacterial infection-related GNs. We highlight these features along with key diagnostic clues and management approach in Bartonella IE-associated GN. We conducted a pooled analysis of 89 cases of Bartonella IE-associated GN (54 published case reports and case series; 18 published conference abstracts identified using an English literature search of several commonly used literature search modalities); and four unpublished cases from our institution. Bartonella henselae and Bartonella quintana are the most commonly implicated species causing IE in humans. Subacute presentation, affecting damaged native and/or prosthetic heart valves, high titer anti-neutrophil cytoplasmic antibodies (ANCA), mainly proteinase-3 (PR-3) specificity, fastidious nature and lack of positive blood cultures of these Gram-negative bacilli, a higher frequency of focal glomerular crescents compared to other bacterial infection-related GNs are some of the salient features of Bartonella IE-associated GN. C3-dominant, but frequent C1q and IgM immunofluorescence staining is seen on biopsy. A "full-house" immunofluorescence staining pattern is also described but can be seen in IE -associated GN due to other bacteria as well. Non-specific generalized symptoms, cytopenia, heart failure and other organ damage due to embolic phenomena are the highlights on clinical presentation needing a multi-disciplinary approach for management. Awareness of the updated modified Duke criteria for IE, a high index of suspicion for underlying infection despite negative microbiologic cultures, history of exposure to animals, particularly infected cats, and use of send-out serologic tests for Bartonella spp. early in the course of management can help in early diagnosis and initiation of appropriate treatment. Diagnosis of IE-associated GN can be challenging particularly with BCNE. The number of Bartonella IE-associated GN cases in a single institution tends to be less than IE due to gram positive cocci, however Bartonella is currently the leading cause of BCNE. We provide a much-needed discussion on this topic.

An Innovative Ayurveda Approach to treat the Idiopathic Edema: A case report

Background: Idiopathic edema is a complex medical condition with limited understanding and challenging choices for treatment. Regarding the Ayurvedic care of idiopathic edema, there aren't many published case reports or clinical trials on PubMed despite the disease's widespread prevalence. In this case report, we propose an important Ayurvedic perspective that takes into consideration the exact location of the manifestation in addition to its origin while selecting methods to treat idiopathic edema. Methods: A 63-year-old male patient complained of persistent right leg edema and blackish discoloration for 18 months while he visited the outpatient department of Kayachikitsa Government Ayurved College & Hospital, Nagpur. In previous times, the patient had sought treatment from doctors who practiced modern medicine without receiving any improvement. The patient was diagnosed as having idiopathic edema after a comprehensive investigation of all possible causes and was then treated according to the Ayurvedic concept of Shoth, which is linked to the origin of Pakwashaya (gut). Along with oral medications, the treatment included Basti (a medicated enema). Results: Interestingly, the patient's quality of life significantly improved, and the edema completely disappeared after the course of treatment. Conclusion: This case study provides insightful information on the importance of disease origin and manifestation sites in the Ayurvedic management of idiopathic edema. It also emphasizes the significance of further research on the role that the gut plays in the pathophysiology of idiopathic edema. 

Nasogastric tube syndrome: A Meta-summary of case reports.

Since its description in 1790 by Hunter, the nasogastric tube (NGT) is commonly used in any healthcare setting for alleviating gastrointestinal symptoms or enteral feeding. However, the risks associated with its placement are often underestimated. Upper airway obstruction with a NGT is an uncommon but potentially life-threatening complication. NGT syndrome is characterized by the presence of an NGT, throat pain and vocal cord (VC) paralysis, usually bilateral. It is potentially life-threatening, and early diagnosis is the key to the prevention of fatal upper airway obstruction. However, fewer cases may have been reported than might have occurred, primarily due to the clinicians' unawareness. The lack of specific signs and symptoms and the inability to prove temporal relation with NGT insertion has made diagnosing the syndrome quite challenging. To review and collate the data from the published case reports and case series to understand the possible risk factors, early warning signs and symptoms for timely detection to prevent the manifestation of the complete syndrome with life-threatening airway obstruction. We conducted a systematic search for this meta-summary from the database of PubMed, EMBASE, Reference Citation Analysis (https://www.referencecitationanalysis.com/) and Google scholar, from all the past studies till August 2023. The search terms included major MESH terms "Nasogastric tube", "Intubation, Gastrointestinal", "Vocal Cord Paralysis", and "Syndrome". All the case reports and case series were evaluated, and the data were extracted for patient demographics, clinical symptomatology, diagnostic and therapeutic interventions, clinical course and outcomes. A datasheet for evaluation was further prepared. Twenty-seven cases, from five case series and 13 case reports, of NGT syndrome were retrieved from our search. There was male predominance (17, 62.96%), and age at presentation ranged from 28 to 86 years. Ten patients had diabetes mellitus (37.04%), and nine were hypertensive (33.33%). Only three (11.11%) patients were reported to be immunocompromised. The median time for developing symptoms after NGT insertion was 14.5 d (interquartile range 6.25-33.75 d). The most commonly reported reason for NGT insertion was acute stroke (10, 37.01%) and the most commonly reported symptoms were stridor or wheezing 17 (62.96%). In 77.78% of cases, bilateral VC were affected. The only treatment instituted in most patients (77.78%) was removing the NG tube. Most patients (62.96%) required tracheostomy for airway protection. But 8 of the 23 survivors recovered within five weeks and could be decannulated. Three patients were reported to have died. NGT syndrome is an uncommon clinical complication of a very common clinical procedure. However, an under-reporting is possible because of misdiagnosis or lack of awareness among clinicians. Patients in early stages and with mild symptoms may be missed. Further, high variability in the presentation timing after NGT insertion makes diagnosis challenging. Early diagnosis and prompt removal of NGT may suffice in most patients, but a significant proportion of patients presenting with respiratory compromise may require tracheostomy for airway protection.

Alpelisib-Induced Diabetic Ketoacidosis: A Pharmacovigilance Analysis of the FDA Adverse Event Reporting System and Review of the Literature

BackgroundAlpelisib is a PI3K inhibitor indicated with fulvestrant for treatment of advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated breast cancer. In the phase III SOLAR-1 trial, grade 3/4 hyperglycemic events were reported in 36.6% of patients receiving alpelisib-fulvestrant compared to 0.7% receiving placebo-fulvestrant. As case reports of diabetic ketoacidosis (DKA) have been associated with alpelisib use, the goal of this study was to characterize the FAERS reported cases of this severe adverse effect. MethodsA retrospective disproportionality analysis was performed using the FAERS database by calculating the reporting odds ratio (ROR) of DKA events with alpelisib from 2019 to 2022. A PubMed literature review of case reports characterizing alpelisib-induced DKA was performed. ResultsPharmacovigilance database analysis revealed significance in reporting among 87 DKA cases with alpelisib (ROR 9.84, 95% confidence interval 7.3-13.2), including hospitalization and death as reported outcomes. Review of 11 published case reports reveals median onset of DKA at 14 days with successful rechallenge possible. ConclusionSignificant association with reporting exists between DKA and alpelisib exposure. We observed similar median time to onset of hyperglycemia between our analysis compared to that reported in SOLAR-1. Considering early onset of this toxicity, it is imperative that patients be closely monitored when initiating alpelisib. Addition of a preemptive antihyperglycemic or escalation in those previously on antihyperglycemic medications is beneficial in decreasing the severity of hyperglycemia with alpelisib. Further study investigating risk factors is warranted to better elucidate which patients require preemptive therapy.

Dispne ile başvuran bir kronik obstruktif akciğer hastasında intrakardiyak kitleden tanı alan skuamoz hücreli karsinom olgusu

Primary cardiac tumor is a rare disease with an incidence ranging from 0.001% to 0.03%. Cardiac metastases are more common than primary tumors. The most frequently metastasized tumors are lung, breast, kidney cancers and melanomas. Several published case reports have documented non-small cell lung cancer (NSCLC) patients with neoplastic heart invasion. However, the number of small cell lung cancer (SCLC) cases with neoplastic cardiac invasion is limited. In this article, we present our case of non-small cell lung cancer with cardiac invasion who presented to the emergency department with dyspnea.

Necrotizing Fasciitis of the Upper Extremity: A Systematic Review of the Literature

Objectives Through this review, we sought to accomplish two goals: 1) analyze and synthesize the published case reports on upper extremity necrotizing fasciitis and 2) identify any trends in the diagnosis and treatment of upper extremity necrotizing fasciitis. Methods Studies included in this systematic review were conducted per PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines with the following eligibility criteria: (1) single case or limited case series, (2) established diagnosis of necrotizing fasciitis in the hand, wrist, or forearm, (3) English language publication. Results Most of the patients in this review (38, (70.37%)) presented with an inciting injury. A minority of patients had other associated co-morbidities independent of injury, including Diabetes Mellitus, immunosuppression, and IV drug use. The most common infectious agents were gram-positive cocci, identified in 32 (59.26%) cases, followed by gram-negative bacilli in 21 (38.89%) cases. The most common pathogen was Group A streptococcus (GAS), reported in 15 (27.78%) cases, followed by Vibrio vulnificus in 6 (11.11%) cases. Most patients were managed with empiric antibiotic treatment. Fifty patients (92.6%) reported surgical intervention and 45 (83.3%) had at least one debridement. Most patients in the cases reviewed had either no or minimal long-term sequelae following their infection. Conclusion Early recognition of the signs and symptoms of necrotizing fasciitis is imperative to avoid loss of limb and/or death. Further, aggressive management with empiric antibiotic coverage and rapid surgical intervention improves outcomes in patients with necrotizing fasciitis of the upper extremity.

Isavuconazole for Treating Invasive Mould Disease in Solid Organ Transplant Recipients.

Solid organ transplant (SOT) recipients have a higher risk of developing invasive mould diseases (IMD). Isavuconazole is a novel broad-spectrum azole active against Aspergillus spp. and Mucor, well tolerated, with an excellent bioavailability and predictable pharmacokinetics, that penetrates in most tissues rapidly, and has few serious adverse effects, including hepatic toxicity. Contrary to other broad-spectrum azoles, such as voriconazole and posaconazole, isavuconazole appears to show significant smaller drug-drug interactions with anticalcineurin drugs. We have performed an extensive literature review of the experience with the use of isavuconazole in SOT, which included the SOTIS and the ISASOT studies, and published case reports. More than 140 SOT recipients treated with isavuconazole for IMD were included. Most patients were lung and kidney recipients treated for an Aspergillus infection. Isavuconazole was well tolerated (less than 10% of patients required treatment discontinuation). The clinical responses appeared comparable to that found in other high-risk patient populations. Drug-drug interactions with immunosuppressive agents were manageable after the reduction of tacrolimus and the adjustment of mTOR inhibitors at the beginning of treatment. In conclusion, isavuconazole appears to be a reasonable option for the treatment of IMD in SOT. More clinical studies are warranted.

Do Poisonous Plants in Pastures Communicate Their Toxicity? Meta-Study and Evaluation of Poisoning Cases in Central Europe.

One of the possible roles of secondary plant metabolites, including toxins, is facilitating plant-animal communication. Lethal cases of pasture poisoning show that the message is not always successfully conveyed. As the focus of poisoning lies in the clinical aspects, the external circumstances of pasture poisoning are widely unknown. To document poisoning conditions in cattle, sheep, goats, and horses on pastures and to compile a checklist of plants involved in either poisoning or co-existence (zero poisoning), published case reports were evaluated as primary sources. The number of affected animal individuals was estimated within abundance classes from 0 to more than 100. The checklist of poisonous plants comprised 52 taxa. Of these, 13 taxa were deemed safe (no reference was found indicating poisoning), 11 taxa were associated with evidence-based zero poisoning (positive list), and 28 taxa were associated with poisoning (negative list). Nine plant taxa caused poisoning in more than 100 animal individuals. Zero poisoning accounted for 40% and poisoning accounted for 60% of a total of 85 cases. Poisoning was most often associated with a limited choice of feed (24.7%), followed by overgrazing (12.9%), seasonally scarce feed (10.6%), and co-ingestion of grass (4.7%). Hunger interferes with plant-animal co-existence, while zero poisoning improves it. In conclusion, poisonous plants in pastures may communicate their toxicity if the animals have enough alternative feed plants. An individual animal might utterly perceive the communication of toxicity by the plant species but be forced to ignore the message owing to a limited choice of feed options.

Mucormycosis of the Mandible and Tongue: A Systematic Scoping Review

Mucormycosis is a rare human infection associated with Mucorales, a group of filamentous moulds found in different environmental niches. Its oral manifestations may occur in the mandible and tongue despite being rare. We aimed to systematically review the data on clinical manifestations, risk factors, diagnostic approaches, treatment options, and outcomes of mandibular and tongue mucormycosis. An electronic search of articles published between January 1975 and November 2022 in PubMed, Web of Science, and EMBASE databases was performed. A total of 22 articles met the inclusion criteria and reported 27 cases of oral mucormycosis in total. Fourteen patients had mandibular mucormycosis signs unrelated to COVID-19 infection, 6 had SARS-CoV-2-related mandibular mucormycosis, and 6 had manifestations in the tongue. All published case reports during the COVID-19 pandemic were from India. Patient ages ranged from 4 months old to 82 years, and most patients had important comorbidities, such as blood dyscrasias related to immune deficiency and uncontrolled type 2 diabetes mellitus. The signs and symptoms of mandibular and tongue mucormycosis varied from dental pain, loose teeth, and nonhealing sockets to dysphagia and paraesthesia of the lip. Some patients also reported trismus, draining sinus tract, and facial pain. The diagnosis of oral mucormycosis was based on a combination of clinical, radiographic, and histopathologic findings by demonstrating fungal hyphae in tissue specimens. In most cases, mucormycosis was managed with systemic amphotericin B, strict glycaemic control, and aggressive surgical debridement of infected tissue, minimising the progression of the fungal infection and thus improving the survival rate. In some cases, combined antifungal therapy, antibiotic therapy, and chlorhexidine mouthwashes were used successfully. Recognition of the signs and symptoms by oral care providers is pertinent for the early diagnosis and treatment of tongue and mandibular mucormycosis, and providers should be aware of the possibility of this opportunistic fungal infection in patients with COVID-19. A multidisciplinary approach is recommended for the management of this lethal infection.

Case Report of an Appendiceal Mucinous Neoplasm: A Rare Etiology for Appendicitis

An appendiceal mucinous neoplasm is a rare condition with a clinical picture that can resemble appendicitis. Published reports have documented an incidence of 0.07-0.3% of all appendicectomies. The ubiquitous use of computerized tomography scans has helped plan surgical strategies as these patients may often require a right hemicolectomy in order to ascertain oncological clearance. This helps the clinician to avoid the complication of pseudomyxoma peritonei with its attendant increased mortality. In this case report the presence of a normal appendix base allowed for a laparoscopic intervention without having to resect the right hemi-colon. All published case reports to date have documented the involvement of the entire appendix. This case report is unique in the sparing of the proximal appendix.

Platelet Response in Pacritinib-Treated Patients with Cytopenic Myelofibrosis: A Retrospective Analysis of PERSIST-2 and PAC203 Studies

Background: Myelofibrosis (MF) is a myeloid malignancy characterized by clonal hematopoisis, bone marrow fibrosis (BMF) and ineffective extramedullary hematopoiesis, resulting in progressive cytopenias. Thrombocytopenia is both prognostic of poor outcomes and predictive of treatment intolerance with the JAK1/2 inhibitor ruxolitinib, which exacerbates cytopenias. Pacritinib is a JAK1-sparing inhibitor of JAK2/IRAK1/ACVR1 that can be administered at full dose to patients regardless of baseline platelet count (PLT). While prior studies have shown that pacritinib is associated with PLT stability in most patients, PLT improvement has not been described outside of a recently published case report ( Yacoub A, et al. JCO Precis Oncol. 2023;7:e2200523). Here, we report rates of hematologic improvement in PLTs (HI-P) with pacritinib across two clinical trials. Methods: Patients with baseline PLT ≤100x10 9/L on the pacritinib 200 mg BID arms of the phase 3 PERSIST-2 study (randomized ≥12 weeks prior to study termination) or the phase 2 dose-finding PAC203 study were included. HI-P was defined per International Working Group (IWG) criteria (baseline PLT <20x10 9/L: increase to >20x10 9/L and by at least 100%; baseline PLT 20-100 x 10 9/L: absolute increase of ≥30x10 9/L) in the absence of PLT transfusions, sustained over any 8 weeks while on treatment. Efficacy outcomes (reduction in spleen volume, symptom score, and BMF) were compared between HI-P responders vs non-responders (those who did not meet IWG criteria). Rates of PLT improvement were also analyzed on the best available therapy (BAT) arm of the PERSIST-2 study over the treatment period (end of study treatment). Results: Of 117 patients randomized to pacritinib (75 from PERSIST-2, 42 from PAC203), 16% (n=19) experienced HI-P on study (as defined in methods). Additionally, 14 of the 19 HI-P patients had sustained platelet improvement over ≥12 weeks). By contrast, only 5% (4/77) of patients on BAT achieved HI-P response prior to end of study treatment. HI-P responders on pacritinib compared to non-responders, had numerically higher median baseline PLT count (63 vs 45x10 9/L) and hemoglobin (Hb; 10.3 vs 8.8 g/dL). A similar percentage had prior (<30 days) JAK2 inhibitor exposure (68.4% vs 66.3%) and JAK2V617F mutation (78.9 vs 74.5%); median JAK2 allele burden was low in both responders and non-responders (26.7% vs 36.9%). Among HI-P responders with prior ruxolitinib exposure, most (85%, 11/13) had recent exposure within the prior 30 days, with median dose of 10 mg BID. PLT improvement was noted within the first 12 weeks in most HI-P responders, whereas PLT count remained stable, on average, among non-responders ( Figure 1a). To evaluate if recent ruxolitinib exposure and washout of drug was responsible for HI-P, we analyzed the subset of patients with ruxolitinib exposure in previous 30 days (11/19). The mean platelet count increased from 56 to 141x10 9/L at week 12. In the remaining 8/19 patients without recent ruxolitinib exposure (n=6 were treatment naïve), platelets increased from 59 to 102 x 10 9/L at week 12. While there was no difference in the magnitude of spleen volume or symptom score reduction in HI-P responders vs non-responders, a correlation with change in BMF was noted. Among the 36 patients with available bone marrow data from baseline and week 24, HI-P responders were numerically more likely to have BMF reduction (67%, n=4/6) compared to non-responders (23%, n=7/30, P=0.057, Figure 1b). There was no difference in the rate of hemorrhagic events (by standardized MedDRA queries) in PLT responders vs non-responders (47% vs 46%), though grade ≥3 bleeding was observed at lower frequency in responders compared to non-responders (10.5% vs 16%). Other commonly reported adverse events with pacritinib occurred at similar frequency between responders and non-responders. Discussion: PLT improvement meeting IWG criteria occurs in a subset of MF patients treated with pacritinib and does not seem to be explained by changes in spleen volume. Further studies are warranted to assess the correlation between hematologic improvement and BMF reduction with pacritinib. It is possible that pacritinib's unique mechanism of action as an IRAK1 inhibitor could result in modulation of the bone marrow microenvironment and thrombopoiesis. Study funded by CTI BioPharma Corp., a Sobi company.

Vitamin B12 Deficiency and Hemolytic Anemia Presenting As Pseudo Thrombotic Microangiopathy: A Systematic Review

Introduction: Vitamin B12 deficiency is a common nutritional issue associated with mild anemia and neurological deficits. While rare, hemolytic anemia and low platelet count can be complications of this deficiency, often misdiagnosed as thrombotic microangiopathy (TMA), specifically thrombotic thrombocytopenic purpura (TTP). Pseudo TMA features can occur with B12 deficiency and can be effectively treated with vitamin B12 supplementation. In contrast, true TMA requires plasmapheresis. This systematic review aims to differentiate between pseudo TMA and TMA cases through an analysis of published case reports, providing valuable insights to avoid unnecessary treatments. Methods: We performed systematic review from Pubmed, Web of Science, and Scopus database. Twin independent reviewers (SY and BL) performed the screening using Covidence. Search keywords included “((hemolytic anemia) AND (vitamin B12 deficiency)) OR ((cobalamin deficiency) AND (hemolytic anemia)) Filters: English” for Pubmed, “(((ALL=(Cobalamin deficiency)) OR ALL=(vitamin B12 Deficiency))) AND ALL=(hemolytic anemia) Filter: English” for Web of Science and “( vitamin AND b12 AND deficiency OR cobalamin AND deficiency ) AND hemolytic AND anemia AND ( LIMIT-TO ( LANGUAGE , ”English“ ))” from Scopus. Only case reports in English with full-text availability and adult subjects were selected. Cases without final clinical outcome after treatment were excluded. After a comprehensive review, we identified 43 case reports and series with a total 53 patients that fulfilled our criteria. The details of selection process is illustrated in the prisma diagram (Figure 1). Results: The majority of cases involved males with low hemoglobin and platelet counts upon admission. Evidence of hemolysis was observed, indicated by increased lactate dehydrogenase (LDH), undetectable haptoglobin, and elevated or normal total and direct bilirubin levels. Peripheral blood films confirmed the presence of hemolytic anemia. Due to the co-occurrence of thrombocytopenia and hemolytic anemia, some cases were initially diagnosed as TTP, leading to the initiation of plasmapheresis. In 16 out of 53 reported case reports/series, patient received plasmapheresis. However, low reticulocyte index and normal ADAMTS 13 suggested an alternative diagnosis. Once ADAMTS 13 levels were normal, plasmapheresis was discontinued as TTP was ruled out. Diagnosis of B12 deficiency was confirmed by low B12 levels and elevated methylmalonic acid (MMA) levels. Leading cause for B12 deficiency were pernicious anemia in 28/53 cases, followed by dietary deficiency, and malabsorption due to surgery. Some patients also exhibiting concurrent iron deficiency anemia and folate deficiency. Treatment with subcutaneous B12 injections showed improvement in hemolysis as early as one week. Conclusion: Many cases of Vitamin B12 deficiency presenting with hemolytic anemia and thrombocytopenia are mistakenly diagnosed as TTP, leading to unnecessary and expensive plasmapheresis. Routine B12 level checks should be performed in all patients with hemolytic anemia, as B12 deficiency can be rapidly diagnosed and effectively treated, avoiding misdiagnoses and unnecessary interventions associated with TTP. The short turnover time for B12 levels (hours) compared to ADAMTS 13 activity (1-2 days) further supports the importance of routine B12 assessment in these patients.