Small extracellular vesicle-loaded bevacizumab reduces the frequency of intravitreal injection required for diabetic retinopathy.

Diabetic retinopathy (DR) is associated with retinal neovascularization, hard exudates, inflammation, oxidative stress and cell death, leading to vision loss. Anti-vascular endothelial growth factor (Anti-VEGF) therapy through repeated intravitreal injections is an established treatment for reducing VEGF levels in the retina for inhibiting neovascularization and leakage of hard exudates to prevent vision loss. Although anti-VEGF therapy has several clinical benefits, its monthly injection potentially causes devastating ocular complications, including trauma, intraocular hemorrhage, retinal detachment, endophthalmitis, etc. Methods: As mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs) demonstrated safety in clinical studies, we have tested the efficacy of MSC-derived small EVs (MSC-sEVs) loaded anti-VEGF drug bevacizumab in a rat model of DR. Results: The study identified a clinically significant finding that sEV loaded with bevacizumab reduces the frequency of intravitreal injection required for treating diabetic retinopathy. The sustained effect is observed from the reduced levels of VEGF, exudates and leukostasis for more than two months following intravitreal injection of sEV loaded with bevacizumab, while bevacizumab alone could maintain reduced levels for about one month. Furthermore, retinal cell death was consistently lower in this period than only bevacizumab. Conclusion: This study provided significant evidence for the prolonged benefits of sEVs as a drug delivery system. Also, EV-mediated drug delivery systems could be considered for clinical application of retinal diseases as they maintain vitreous clarity in the light path due to their composition being similar to cells.

Leukocytoclastic Vasculitis: A peculiar presentation of scrub typhus.

Scrub typhus is a disease endemic to the Indian subcontinent caused by the obligate intracellular pleomorphic organism, Orientia tsutsugamushi. Scrub typhus, among other acute febrile illnesses, manifests as prodromal symptoms of fever, malaise, myalgia and anorexia followed by a distinct maculopapular rash, hepatosplenomegaly and lymphadenopathy. We report the case of a patient presenting to tertiary care hospital in southern India in 2021 who developed a rare cutaneous vasculitis secondary to infection with Orientia tsutsugamushi. After performing the Weil-Felix test, a diagnostic titre of >1:640 against OXK was obtained. Furthermore, a skin biopsy was carried out which confirmed the diagnosis of leukocytoclastic vasculitis. The patient was treated with doxycycline and showed drastic improvement in his symptoms.

Cutaneous ulceration as a presenting feature of type 1 lepra reaction: A case report.

Reactions in leprosy represent sudden shift in the immunological response and are seen in 11-25% of affected patients. It can be seen before, during or after the completion of multidrug therapy (MDT).1 Two types of reactions are recognized; Type 1 reaction (T1R), seen in borderline leprosy, affecting mainly skin and nerves; type 2 reaction (T2R) or erythema nodosum leprosum (ENL), seen in lepromatous leprosy, characterized by systemic features in addition to cutaneous lesions. Trophic ulcers and ulcerating ENL are well known entities while cutaneous ulceration in T1R is extremely rare; we describe an immune-competent woman with cutaneous ulceration as a presenting feature to highlight the need to recognize this entity at the earliest opportunity.

An eye-opening case of periorbital oedema: a clinicodiagnostic dilemma.

Cutaneous metastasis (CM), a rare occurrence, can produce a variety of skin lesions. Signet-ring cell carcinoma (SRCC) is a very aggressive tumour with low survival rate irrespective of location. We report a case of SRCC with CM presenting with asymptomatic progressive unilateral angio-oedema-like findings. A high index of suspicion and low threshold for biopsy are crucial for early diagnosis of CM as the prognosis is poor, especially when the primary cancer is SRCC.

Aggressive-fungating retinal hemangioblastoma.

Retinal hemangioblastomas are one of the most common and early manifestations of Von Hippel-Lindau disease. Early detection is the key in their management. When left untreated, these benign neoplasms may continue to grow and result in scleral infiltration and extraocular extension warranting enucleation of the globe.

A case of false identity: Primary cutaneous diffuse large B-cell lymphoma masquerading as Madura Foot.

Primary cutaneous - diffuse large B-cell lymphoma - leg type (PC-DLBCL-LT) is a less frequent but more aggressive, and potentially curable, type of cutaneous B-cell lymphoma, with intermediate prognosis, that affects elderly individuals. Our patient with indurated, pigmented foot previously treated for Filariasis, now presented with ulcers, multiple discharging sinuses, clinically suspected to have Madura Foot. Histopathological examination confirmed a diagnosis of PC-DLBCL-LT after which he underwent below-knee amputation.

Quadriplegia and rhabdomyolysis as a presenting feature of Conn's syndrome.

Conn's syndrome is an important endocrine cause for secondary hypertension. Hypokalaemia paralysis and rhabdomyolysis with accelerated hypertension may be the presenting symptoms of Conn's syndrome. Here, we present one such case of a 38-year-old woman presenting with accelerated hypertension and acute onset quadriplegia. On biochemical evaluation, she was found to have severe hypokalaemia, metabolic alkalosis and elevated creatinine phosphokinase. Further evaluation revealed an elevated aldosterone renin ratio suggestive of primary hyperaldosteronism which was localised to left adrenal adenoma on contrast-enhanced CT. Patient's blood pressure and serum potassium levels normalised after resection of the adrenal adenoma.

Cold en bloc excision (CEBE) of bladder tumours using Zedd excision scissors: a prospective, pilot, safety and feasibility study.

BACKGROUND: Transurethral resection of bladder tumour (TURBT) is the traditional technique of choice for endoscopically suspected bladder tumours. Cold En Bloc Excision (CEBE) using novel Zedd scissors is proposed for endoscopic treatment of patients with non-muscle invasive bladder cancer (NMIBC). The aim of this study was to evaluate feasibility and safety of CEBE of bladder tumours using Zedd scissors. METHODS: A pilot prospective study of patients who underwent a CEBE of suspicious bladder tumours using Zedd scissors was conducted. A total of 23 patients underwent CEBE for suspected bladder tumours using Zedd scissors. New and recurrent tumours <3 cm were included in the study. The outcome measures were the presence of detrusor muscle (DM) and obturator nerve reflex (ONR), bladder perforation rates, specimen cautery artefacts, recurrence rates and complication rates. The mean age was 64 years ± 10.41 (range: 49-83 years). The median follow up was 4 months (range 1-9 months). The mean tumour size was 1.8 cm ± 0.40 (range: 0.8-2.6 cm). Tumours were located in the lateral wall (n = 11), dome (n = 2), posterior wall (n = 6), trigone (n = 2), anterior wall (n = 4) and the junction of lateral and posterior wall (n = 4). RESULTS: There was no ONR or bladder perforation and none of the patients had any complications. DM was present in 21 patients (91%). There was no tumour identified at the circumferential margins. There was no cautery artefact reported in any case. No patients had a recurrence at first follow up cystoscopy and two patients had out of field recurrence at subsequent cystoscopies. CONCLUSION: CEBE with Zedd scissors is a promising en bloc excision technique for bladder tumour. It is a safe and feasible for excision of tumours less than 3 cm. The early oncological outcomes are comparable with existing en bloc resection techniques (ERBT) for NMIBC.

Syndrome of inappropriate antidiuretic hormone release as the initial presentation of adenocarcinoma of the colon.

Syndrome of inappropriate antidiuretic hormone release (SIADH) is a condition defined by the unsuppressed release of antidiuretic hormone (ADH) from the pituitary gland or nonpituitary sources or its continued action on vasopressin receptors. Of the many causes of SIADH, an important one includes tumours that secrete ADH. We describe a rare case of a patient with colonic adenocarcinoma presenting initially as SIADH. A 60-year-old man presented with confusion and vomiting. Over the previous month he had fatigue and loss of weight. Baseline investigations showed a low serum sodium level of 108mmol/l. He was euvolaemic on examination and fulfilled the criteria for SIADH. Further evaluation and imaging tests revealed that the patient had adenocarcinoma of the colon. It is remarkable that our patient did not present with any of the cardinal symptoms/signs suggestive of colorectal carcinoma including haematochezia, change in bowel habits or iron-deficiency anaemia. Initial therapy with hypertonic saline, fluid restriction and salt diet for management of SIADH was unsuccessful. Tolvaptan was added to the treatment regimen and the patient improved dramatically. Oncology consultation was initiated, and chemotherapy for the carcinoma was planned.

Generalized hypertrophic lichen planus: an atypical presentation of a characteristic disease.

Lichen planus is a common chronic inflammatory condition that affects skin and mucous membranes. Management is often delayed because of patient embarrassment or misdiagnosis by the clinician. Early recognition and treatment is essential to reduce the morbidity of this condition. We present a 58-year-old woman diagnosed with generalized hypertrophic lichen planus, a rare event, reported to occur usually on lower extremities, but found to be generalized in our patient, requiring excision of symptomatic lesions. We suggest a multidisciplinary approach to allay the anxiety and symptoms of these patients and to improve the quality of life and clinical outcomes.

Granuloma multiforme: an uncommon differential for leprosy.

Granuloma multiforme (GM) is a chronic granulomatous skin condition which is clinically characterised by annular lesions mainly over sun-exposed areas and histologically by focal necrobiosis and histiocytic granulomas. Its significance lies in the fact that it can clinically resemble tuberculoid leprosy and hence it can be missed. Here, we report a case of GM from India in a 55-year-old female agriculturist, with multiple asymptomatic large annular rings of papules over the photo-distributed areas. Histopathology helps in confirming the diagnosis and in differentiating it from similar clinical and histologic mimics such as granuloma annulare, tuberculoid leprosy, interstitial granulomatous dermatitis or annular sarcoid. Though a high degree of suspicion is needed to diagnose GM, it should be considered as a differential for various annular conditions.

Pediatric cranial intraosseous hemangiomas: a review.

Hemangiomas are benign, slow-growing tumors composed of sinusoidal blood vessels. Skeletal hemangiomas are uncommon and are mostly vertebral, followed by cranial in location. Cranial hemangiomas are very rarely encountered in children. Authors report a 12-year girl who presented with a painless enlarging mass over the parietal scalp for 3 months. Imaging revealed a left parietal intraosseous lytic mass with a sunburst appearance. Enbloc removal and cranioplasty was performed, and histopathology was suggestive of hemangioma. We reviewed the literature on pediatric cranial intraosseous hemangiomas (PCIH) (age ≤18 years) by searching online database. Including ours, a total of 24 cases were analyzed. Mean age was 10.2 years (range 4 months-17 years). Eight were in the first decade and 16 were in the second decade. Male:female ratio was 12:12 (1:1). A painless palpable mass was the commonest presenting feature. Parietal and frontal bones were most commonly involved. Intracranial extension was noted in cases. Mean size of the lesion was 5 cm (range 1-12 cm). Twenty-two underwent primary surgical removal while two had additional pre-operative embolization. Surgical procedures were craniectomy alone (n-3), craniectomy + cranioplasty (n-6), tumor excision + remodeling (n-3), and tumor debulking (n-2). Histopathology was cavernous type in majority of cases. Mean follow-up duration was 11.8 months (range 2-38 months). There were no recurrences. One patient died due to systemic infection. Ours is the first review exclusively on PCIH. Although rare, they need to be considered in the differential diagnosis of lytic skull lesions in children. Enbloc removal with cranioplasty is the preferred treatment in vault hemangiomas, while embolization followed by debulking would suffice in large cranial base lesions.