Vaginal pessary: a culprit for intraperitoneal bladder perforation.

Vaginal pessaries are widely considered to be a safe and effective non-surgical management option for women with pelvic organ prolapse. Complications may occur, and are more frequent with improper care and certain device designs and materials. It is imperative to provide information to patients about potential complications. We present the case of a woman in her 70s who presented to the Emergency Department with increasing groin and abdominal pain following a vaginal pessary insertion 2 days prior for grade 3 vaginal vault prolapse. On presentation, her abdomen was markedly distended with guarding. Laboratory investigations showed a significant acute kidney injury with a metabolic acidosis. An initial non-contrast CT showed fluid and inflammatory changes surrounding the bladder, and bladder perforation was suspected. A subsequent CT cystogram showed extravasation of contrast from the bladder into the peritoneal cavity, in keeping with an intraperitoneal bladder rupture. The patient underwent an emergency bladder repair in theatre.

Controlling CAR-T cell activity and specificity with synthetic SparX adapters.

While conventional chimeric antigen-receptor (CAR)-T therapies have shown remarkable clinical activity in some settings, they can induce severe toxicities and are rarely curative. To address these challenges, we developed a controllable cell therapy where synthetic D-domain-containing proteins (soluble protein antigen-receptor X-linker [SparX]) bind one or more tumor antigens and mark those cells for elimination by genetically modified T cells (antigen-receptor complex [ARC]-T). The chimeric antigen receptor was engineered with a D-domain that specifically binds to the SparX protein via a unique TAG, derived from human alpha-fetoprotein. The interaction is mediated through an epitope on the TAG that is occluded in the native alpha-fetoprotein molecule. In vitro and in vivo data demonstrate that the activation and cytolytic activity of ARC-T cells is dependent on the dose of SparX protein and only occurs when ARC-T cells are engaged with SparX proteins bound to antigen-positive cells. ARC-T cell specificity was also redirected in vivo by changing SparX proteins that recognized different tumor antigens to combat inherent or acquired tumor heterogeneity. The ARC-SparX platform is designed to expand patient and physician access to cell therapy by controlling potential toxicities through SparX dosing regimens and enhancing tumor elimination through sequential or simultaneous administration of SparX proteins engineered to bind different tumor antigens.

Red in the face: Approach to diagnosis of red rashes on the face.

BACKGROUND: A red rash on the face in an adult patient is a common presentation to general practice in Australia. Rashes on the face significantly affect quality of life because this is a cosmetically sensitive site. Ascertaining the correct diagnosis is therefore of utmost importance so that appropriate treatment can be initiated. OBJECTIVE: This article discusses the assessment of red rashes on the face in an adult patient. DISCUSSION: Diagnosing a red rash on the face requires assessment of symptomology, age of onset, rash morphology and 'clinical clues' that help delineate between differentials. Although the list of differential diagnoses is wide, many of the common diagnoses can be made clinically without the need for investigations. Investigations such as skin biopsy are useful if the diagnosis is unclear, if the rash is not responding to initial treatment and/or a referral to a dermatologist is being considered.

Approach to red, scaly eruptions in the older patient.

BACKGROUND: Older patients with a red scaly eruption often present first to a primary care practitioner. A thorough clinical assessment can help delineate between common causes and assist the clinician with the next steps in management. OBJECTIVE: This article discusses the assessment of acute- to subacute-onset erythematous and scaly plaques that are present on multiple body sites in a patient aged >65 years. DISCUSSION: The differential diagnosis of a red, scaly rash in an older patient includes atopic dermatitis, psoriasis, generalised drug eruption, tinea, scabies and non-bullous pemphigoid. Less common causes include subacute cutaneous lupus and mycosis fungoides. If the diagnosis is unclear after clinical assessment, a skin biopsy sent for histopathology, and/or direct immunofluorescence can be very useful. Management requires consideration of physical impairments, carer availability and cost.

Left-sided cholecystitis in a patient with situs inversus totalis, complicated by portal venous malformations.

Situs inversus totalis (SIT) is a rare autosomal recessive anomaly in which the thoracoabdominal viscerae are laterally transposed, introducing unique challenges in surgical scenarios. Only a few reports have demonstrated the treatment of cholecystitis in situs inversus, much less so in the context of portal vascular anomalies. We present the case of a 41-year-old female presenting to the emergency department with right upper quadrant pain, and subsequently found to have left-sided cholecystitis complicated by SIT with portal venous malformations on magnetic resonance cholangiopancreatography and abdominal computed tomography. Initially, she was referred for open cholecystectomy however due to the lack of symptoms and the presence of a tortuous recanalized portal vein presenting multiple thrombotic complications, an expectant approach was adopted. Thus, imaging remains the gold-standard to diagnose SIT and consideration of all congenital risk factors to cholecystectomy is crucial to avoid post-operative complications.

A systematic review exploring the mechanisms by which citrus bioflavonoid supplementation benefits blood glucose levels and metabolic complications in type 2 diabetes mellitus.

BACKGROUND: Citrus bioflavonoids are polyphenolic compounds that are derived from citrus fruits and vegetables. Although they are well known for their powerful antioxidant properties, their effects on glycemic control are not well understood. This review aims to highlight the potential benefits of using citrus bioflavonoids in patients with type 2 diabetes mellitus and its metabolic complications, as well as the medicinal effects of known subclasses of naturally occurring citrus bioflavonoids. METHODS: In this systematic review, a survey of studies was conducted from January 2012 to February 2023 using various databases (PubMed, Medline, Google Scholar, and Scopus) to determine the effects of citrus bioflavonoid supplementation on reducing oxidative stress, improving lipid profiles, and glycemic index in patients with diabetes mellitus, as well as the proposed mechanisms of action. RESULTS: The results of the survey indicate that citrus bioflavonoids may have a positive impact on reducing oxidative stress levels in patients with type 2 diabetes mellitus. In addition to reducing oxidative stress, citrus bioflavonoids may also have a positive impact on other markers of diabetes. For example, studies have shown that they can reduce non-enzymatic protein glycation, which is a process that occurs when glucose molecules bind to proteins in the body. CONCLUSION: The reduction in oxidative stress that can be achieved using citrus bioflavonoids may help to maintain antioxidant levels in the body, thereby reducing the severity of diabetes and its complications. These findings suggest that citrus bioflavonoids may be a useful complementary therapy for patients with diabetes.

Stage Migration in Renal Malignancies in COVID Era: A Single-Center Analysis.

The COVID-19 disease, caused by SARS-CoV-2 virus, attained the status of a pandemic by March 2020. There was apprehension among patients suffering from renal malignancies about balancing cancer treatment and preventing COVID-19 infection transmission. We analyzed 184 patients with renal malignancies retrospectively, who presented to our institute over 2 years: 91 patients of renal malignancies in pre-COVID era (March 2019-Feb 2020) and 93 patients in COVID era (March 2020-Feb 2021). The parameters analyzed were age, tumor size, clinical presentation, clinical stage, pathological stage, nuclear grade, and presence of metastasis. Level of significance was kept at 95%, and p value <0.05 was considered significant. The age of patients was comparable in both groups (p: 0.381). Clinical presentation was also similar in both groups whereas there were more cases diagnosed during routine evaluation in pre-COVID era (p: 0.022). Tumor size was 5.84 ± 3.03cm vs. 7.10±3.83cm (p: 0.017) in pre-COVID vs. COVID era, respectively. Patients in COVID era had significantly higher clinical stage (p = 0.041), pathological stage (p =0.027), nuclear grade (p = 0.007), and presence of metastasis (p = 0.005) as compared to pre-COVID era. Patients, who underwent Nephron-sparing surgery, also had higher pathological stage in COVID era. COVID overshadowed the management of renal malignancies. There was a clear shift and stage migration in patients of renal malignancies in COVID era as compared to pre-COVID era, probably because of less routine health check-ups and patients deferring hospital visits due to fear of contracting COVID infection.

Iron Deficiency Anemia as a Potential Risk Factor for Unprovoked DVT in Young Patients: A Case Series.

Deep vein thrombosis (DVT) is a serious and potentially life-threatening condition due to the occurrence of pulmonary embolism (PEs) in the acute phase. DVT can be provoked or unprovoked. Provoked DVT can be associated with transient or persistent causes. Iron deficiency anemia (IDA) with reactive thrombocytosis can act as a prothrombotic condition. We present two case reports of lower limb DVT which was associated with moderate anemia. Association between IDA and thrombosis has been reviewed.

Ureteral transitional cell carcinoma with supraclavicular lymph node metastasis: a case report.

Metastasis to the supraclavicular lymph nodes usually originate from primary tumours in the head and neck, breast or abdomen. Infradiaphragmatic tumours very rarely metastasise to these nodes. Transitional cell carcinomas (TCCs), also termed urothelial carcinomas, account for ⁓90% of all ureteral cancers; exceptionally few cases have reported such cancers spreading to the supraclavicular fossae. We present the case of a 65-year-old male who was being investigated for gallstones and was subsequently found to have metastatic bony lesions and widespread adenopathy on magnetic resonance cholangiopancreatography. Initially, the primary cancer was an area of contention between clinicians, as radiologists suggested it was of urological origin, but the bladder multidisciplinary team felt the scans did not fulfil this notion. Ultimately, histological analysis confirmed the diagnosis of metastatic TCC.

Pseudomyxoma peritonei and an incidental low-grade appendiceal mucinous neoplasm and neuroendocrine appendiceal collision tumour: a case report.

Appendiceal collision tumours are extremely rare, with most reported cases describing tumours consisting of a mucinous component and a neuroendocrine component. Low-grade appendiceal mucinous neoplasms, in some cases, have a tendency to rupture and disseminate their mucin-producing cells throughout the abdominal cavity, leading to a clinical syndrome known as pseudomyxoma peritonei (PMP). We present the case of a 64-year-old male who initially presented with acute appendicitis and was subsequently found to have PMP and appendiceal malignancy. After several years of scans, surgical intervention and histological analysis, it became apparent that the appendiceal malignancy was comprised of distinct cell types. The patient underwent two rounds of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy, which resulted in a 2-year disease-free period. Unfortunately, the PMP recurred, having morphological changes consistent with a more aggressive disease process.

Right upper lobe pulmonary sequestration masquerading clinically and radiologically as malignancy: a case report.

Bronchopulmonary sequestration is a rare disease in which a non-functional region of pulmonary tissue receives an aberrant vascular supply and lacks normal communication with the tracheobronchial tree. We present the case of a 30-year-old female with a primary complaint of unexplained weight loss and no other additional signs or symptoms. In view of this, computed tomography imaging was ordered, showing a 33HU mass in the right upper lobe. A specialist radiologist reviewed the images and concluded that the most likely differentials were mediastinal lymphoma or thymic malignancy. Video-assisted thoracoscopic surgery was performed, when it was seen that no malignancy was present, but rather a bronchopulmonary sequestration. Histology confirmed the diagnosis; the patient fared well post-operatively. Bronchopulmonary sequestration is a rare pathology, with most cases occurring in the lower lung lobes. This case is highly atypical, due to the lack of clinical features and the lesion radiologically mimicking the appearance of malignancy.

Spinal cord involvement in COVID-19: A review.

Context: Recent literature points towards myelitis, like encephalitis, as a common central nervous system complication of COVID-19. This review elaborates on disorders of the spinal cord caused by the SARS-CoV-2 virus.Objectives: To review the published data about SARS-CoV-2-associated spinal cord disorders and assess their clinical, neuroimaging, treatment, and prognostic aspects.Methods: The PubMed and Google Scholar databases were searched for published cases using the search items "COVID-19 OR SARS-CoV-2 AND myelitis", "COVID-19 OR SARS-CoV-2 AND myelopathy", and "COVID-19 OR SARS-CoV-2 AND spinal cord".Results: Thirty-three isolated cases were included in the present review, of which 14 were aged 60 years and above (range: 3-70 years). Eighteen patients had lung abnormalities on chest imaging. Eight patients had developed either an areflexic paraparesis or quadriparesis. In 17 patients, neuroimaging demonstrated longitudinally extensive transverse myelitis, while 3 cases showed neuroimaging changes in the spinal cord as a part of acute disseminated encephalomyelitis syndrome. Cerebrospinal fluid (CSF) examinations revealed inflammatory changes in 18 patients. However, the SARS-CoV-2 virus in the CSF was discovered in 2 patients. In 2 patients, anti-SARS-CoV-2 antibodies were demonstrated in the CSF. Following treatment, 13 patients were able to walk.Conclusions: A variety of COVID-19-related spinal cord manifestations, such as acute transverse myelitis, acute necrotizing myelitis, SARS-CoV-2 myelitis, acute disseminated encephalomyelitis, neuromyelitis optica spectrum disorder, hypoxic myelopathy, MOG antibody-associated myelitis, spinal cord infarction, and spinal epidural abscess, have been reported. The possible mechanisms of this involvement being direct invasion, cytokine storm, coagulopathy, and an autoimmune response. However, response to treatment has been generally unsatisfactory, with many patients having residual weakness necessitating long-term rehabilitation.

Pollution free UV-C radiation to mitigate COVID-19 transmission.

The high rate of transmission of the COVID-19 virus has brought various types of disinfection techniques, for instance, hydrogen peroxide vaporization, microwave generating steam, UV radiation, and dry heating, etc. to prevent the further transmission of the virus. The chemical-based techniques are predominantly used for sanitization of hands, buildings, hospitals, etc. However, these chemicals may affect the health of humans and the environment in unexplored aspects. Furthermore, the UV lamp-based radiation sanitization technique had been applied but has not gained larger acceptability owing to its limitation to penetrate different materials. Therefore, the optical properties of materials are especially important for the utilization of UV light on such disinfection applications. The germicidal or microorganism inactivation application of UV-C has only been in-use in a closed chamber, due to its harmful effect on human skin and the eye. However, it is essential to optimize UV for its use in an open environment for a larger benefit to mitigate the virus spread. In view of this, far UV-C (222 nm) based technology has emerged as a potential option for the sanitization in open areas and degradation of microorganisms present in aerosol during the working conditions. Hence, in the present review article, efforts have been made to evaluate the technical aspects of UV (under the different spectrum and wavelength ranges) and the control of COVID 19 virus spread in the atmosphere including the possibilities of the human body sanitization in working condition.

Analysis of Citrus Bioflavonoid Content and Dipeptidyl Peptidase-4 Inhibitory Potential of Commercially Available Supplements.

Citrus bioflavonoids are polyphenolic plant-derived pigments found in high levels in oranges, lemons, grapefruits and other citrus fruits. The three most abundant types of citrus bioflavonoids are hesperidin, naringenin and eriocitrin. Citrus bioflavonoids have long been known to possess powerful free radical-scavenging properties and cardioprotective effects. The study involved the analysis of 10 commercially available citrus bioflavonoid supplements from three different countries: Australia, the United States and Canada. The supplements were tested for their citrus bioflavonoid content which varied from 0.8 to 33.3% w/w. The daily bioflavonoid dose varied from 19 mg to 560 mg. Hesperidin was the major citrus bioflavonoid in nine out of ten supplements. One supplement was found to contain less than 10% of the quantity of rutin claimed to have been added. The DPP-4 inhibitory potential, compared through an estimation of rutin equivalence, ranged from 1.9 mg to 400 mg per day. This data highlights the variability between the supplements in their potential to inhibit DPP-4 for subsequent health benefits.

Preclinical Efficacy of BCMA-Directed CAR T Cells Incorporating a Novel D Domain Antigen Recognition Domain.

Chimeric antigen receptor (CAR) T-cell therapies directed against B-cell maturation antigen (BCMA) have shown compelling clinical activity and manageable safety in subjects with relapsed and refractory multiple myeloma (RRMM). Prior reported CAR T cells have mostly used antibody fragments such as humanized or murine single-chain variable fragments or camelid heavy-chain antibody fragments as the antigen recognition motif. Herein, we describe the generation and preclinical evaluation of ddBCMA CAR, which uses a novel BCMA binding domain discovered from our D domain phage display libraries and incorporates a 4-1BB costimulatory motif and CD3-zeta T-cell activation domain. Preclinical in vitro studies of ddBCMA CAR T cells cocultured with BCMA-positive cell lines showed highly potent, dose-dependent measures of cytotoxicity, cytokine production, T-cell degranulation, and T-cell proliferation. In each assay, ddBCMA CAR performed as well as the BCMA-directed scFv-based C11D5.3 CAR. Furthermore, ddBCMA CAR T cells demonstrated in vivo tumor suppression in three disseminated BCMA-expressing tumor models in NSG-immunocompromised mice. On the basis of these promising preclinical data, CART-ddBCMA is being studied in a first-in-human phase I clinical study to assess the safety, pharmacokinetics, immunogenicity, efficacy, and duration of effect for patients with RRMM (NCT04155749).

The effect of norepinephrine on clinical and hemodynamic parameters in neonates with shock: a retrospective cohort study.

There is limited data on the cardiovascular effects of norepinephrine (NE) in neonates. Our objective was to describe the clinical responses in neonates treated with NE infusion. This retrospective cohort study included neonates with evidence of shock and those who received NE infusion. PRIMARY OUTCOME: changes in mean blood pressure (MBP) at 6, 12, and 24 h post-initiation of NE. SECONDARY OUTCOMES: Changes in (i) diastolic BP, systolic BP, and vasoactive inotrope score (VIS) at 6, 12, and 24 h, (ii) urine output after initiation of NE ii) pH, lactate, fraction of inspired oxygen (FiO2) after initiation of NE, and (iv) adverse outcomes. Fifty infants received NE with mean (SD) gestational age of 34.3 (4.3) weeks and a mean birth weight of 2215 (911) g. Treatment began at a median age of 36 (IQR: 15.2, 67.2) hours of life and lasted 30.5 (IQR: 12.7, 58) hours. MBP improved from 34.4 mm Hg (SD: 6.6) at baseline to 39.4 mm Hg (SD: 10.5, p < 0.001) at 6 h, to 39.6 mm Hg (SD: 12.1, p = 0.002) at 12 h and to 40.4 mm Hg (SD: 15.5, p = 0.004) at 24 h after NE initiation. Vasoactive inotrope score declined from 30 (20, 32) to 10 (4, 30; p < 0.001) at 24 h. Urine output improved within 24 h [1.5 ml/kg/h (0.5, 2.3) at baseline to 3 (1.9, 4.3) at 24 h; p = 0.04]. Oxygen requirement decreased after NE initiation. CONCLUSION: The use of NE appears to be effective and safe for treating systemic hypotension in neonates. TRIAL REGISTRATION: Being a retrospective study, trial registration was not considered. WHAT IS KNOWN: • Dopamine has traditionally been used as the initial agent for treatment of neonatal hypotension. • Norepinephrine has recently been recommended as the first-choice vasopressor agent to correct hypotension in adults and pediatric patients, with insufficient data on the cardiovascular effects of NE in neonates What is new: • Mean blood pressure improved significantly at 6, 12, and 24 h with reduction in vasoactive infusion score at 12 and 24 h after norepinephrine infusion. • No significant change in heart rate or abnormal abdominal adverse effects noted in this study.

NDK/NME proteins: a host-pathogen interface perspective towards therapeutics.

No effective vaccine is available for any parasitic disease. The treatment to those is solely dependent on chemotherapy, which is always threatened due to development of drug resistance in bugs. This warrants identification of new drug targets. Here, we discuss Nucleoside diphosphate kinases (NDKs) of pathogens that alter host's intra and extracellular environment, as novel drug targets to simultaneously tackle multiple pathogens. NDKs having diverse functions, are highly conserved among prokaryotes and eukaryotes (the mammal NDKs are called NMEs [non-metastatic enzymes]). However, NDKs and NMEs have been separately analysed in the past for their structure and functions. The role of NDKs of pathogen in modulation of inflammation, phagocytosis, apoptosis, and ROS generation in host is known. Conversely, its combined contribution in host-pathogen interaction has not been studied yet. Through the sequence and domain analysis, we found that NDKs can be classified in two groups. One group comprised NMEs 1-4 and few NDKs of select essential protozoan parasites and the bacterium Mycobacterium tuberculosis. The other group included NME7 and the other NDKs of those parasites, posing challenges in the development of drugs specifically targeting pathogen NDKs, without affecting NME7. However, common drugs targeting group 2 NDKs of pathogens can be designed, as NME7 of group 2 is expressed only in ciliated host cells. This review thus analyses comparatively for the first time the structures and functions of human NMEs and pathogen NDKs and predicts the possibilities of NDKs as drug targets. In addition, pathogen NDKs have been now provided a nomenclature in alignment with the NMEs of humans.

Bowen's disease on two different unrelated anatomical sites (genitals and nail) in succession in an immunocompromised patient.

Bowen's disease (BD) is a premalignant condition. Its exact etiology is unknown but chronic arsenic and sun exposure, and human papillomavirus infection is known predisposing factors. Pigmented lesions of BD represent 1.7%-5.5% of all BD cases. BD in the nail unit is challenging due to its varied clinical presentations such as fissure, ulceration, warty lesion, paronychia, onychocryptosis, and nail dystrophy. We present the case of a 43-year-old married, immunocompromised male (HIV), with a CD 4 count of 478, on tenofovir, atazanavir boosted with ritonavir regimen, known diabetic presented with multiple asymptomatic discrete, rounded, hyperpigmented verrucous papules on both surfaces of shaft of penis and scrotum and a single, 4 cm × 3 cm, irregular, smooth surfaced, hyperpigmented plaque, on the base of the penis extending to the upper part of the scrotum of 1-year duration with history of multiple unprotected sexual exposures with unknown female partners. Regional lymphadenopathy and systemic complaints were absent. Biopsy from hyperpigmented verrucous papule and hyperpigmented plaque was consistent with verruca vulgaris and pigmented Bowen's disease, respectively. The patient was lost to follow-up. Ten months later, he presented with longitudinal melanonychia with a subungual hyperpigmented mass protruding beyond the distal nail margin near the lateral nail fold of the right middle finger nail with an absent Hutchinson's sign. Longitudinal excisional biopsy of nail lesion was consistent with BD. He was started on 5-fluorouracil 5% for BD of genitals and podophyllin application for verruca vulgaris with remarkable improvement in both the lesions and there is no recurrence of nail lesion after 9 months of excision.

Successful Multimodality Management of Atypical Teratoid/Rhabdoid Tumour of the Lower Dorsal Spine with Spinal Drop Metastasis: Illustrated Review.

INTRODUCTION: Spinal atypical teratoid/rhabdoid tumour (AT/RT) is exquisitely rare and constitutes 2% of all AT/RTs. CASE PRESENTATION: A 6-year-old boy presented with low backache for the last 5 months. MRI of the spine showed a 1.5 × 1.5 × 4.7 cm intradural extramedullary mass extending from D10 to D12, causing compression of the conus medullaris. With a preoperative diagnosis of ependymoma, a gross total resection (GTR) of tumour was performed. Post-operative histopathology showed AT/RT. The tumour cells were immunopositive for cytokeratin, epithelial membrane antigen, smooth muscle actin, and p53 and immunonegative for MIC2, desmin, glial fibrillary acidic protein, and INI1. Post-operative neuraxis MRI revealed post-operative changes (D10-D12) with a 9 mm enhancing lesion at L5-S1 junction suggesting drop metastasis. There was no lesion in brain. Cerebrospinal fluid cytology did not show any malignant cell. The metastatic work-up was normal. He received 3 cycles of chemotherapy with ICE regimen (ifosfamide, carboplatin, and etoposide). Subsequently, he received craniospinal irradiation (CSI)-36 Gy/20 fractions/4 weeks followed by focal boost to primary tumour bed and spinal drop metastasis-14.4 Gy/8 fractions/1.5 weeks. Thereafter, he received 3 more cycles of ICE regimen. End-of-treatment MRI spine showed post-op changes (D10-D12) and 38.9% reduction of the L5-S1 lesion suggesting partial response. Six monthly spinal MRI showed serial reduction of the metastatic lesion leading to complete response (CR) 1 year after completion of treatment. On last follow-up (30 months from the initial diagnosis), he was neurologically intact and in CR. CONCLUSION: Multimodality management comprising GTR of tumour, CSI followed by focal boost, and multiagent chemotherapy (ICE) can lead to successful outcome in patients with this rare and aggressive spinal tumour.