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Phrenic nerve injury (PNI) remains a clinically relevant complication of atrial fibrillation (AF) ablation, and contemporary device-specific risk and recovery data are limited. We analyzed a large multicenter database to compare PNI incidence across device platforms. This prospective observational study consisted of 19,764 consecutive AF ablations at 20 centers between January 2022 and November 2025. PNI was defined as elevation of the right hemidiaphragm on the next-day post-procedural chest X-ray. PNI occurred in 202 patients; 24 were attributed to radiofrequency ablation (RFA) and 178 to non-RFA during right superior or inferior pulmonary vein (RSPV/RIPV) isolation (Arctic Front Advance [AFA] 43, POLARx 62, POLARx FIT 69, laser balloon 1, hot balloon 2, and pulsed field ablation (1). Cryoballoon-related PNI incidence differed by platform (AFA 1.7%&#xa0;vs. POLARx 4.1%&#xa0;versus POLARx FIT 4.2%; overall P<0.001), with Holm-adjusted differences for AFA versus POLARx/POLARx FIT (both P<0.001). In the cryoballoon cohort, younger age (odds ratio [OR] 0.98), female sex (OR 1.94), lower body mass index (BMI) (OR 0.94), deep sedation/general anesthesia (OR 2.0, vs. light sedation), and POLARx/POLARx FIT use (OR 2.43/2.72, vs. AFA) were independently associated with PNI. Overall recovery was observed in 187/202 (92.6%). Recovery curves differed by presumed injury site (p = 0.006), with faster recovery for RSPV- (vs. RIPV-related PNI); RFA-related PNI during superior vena cava/right atrial ablation tended to recover more slowly. The cryoballoon platform was associated with PNI risk, while most PNIs recovered; recovery time course varied by presumed injury site and BMI.

Melanoma has an excellent prognosis when detected at a localized stage, but when patients present with regional or distant metastases, 5-year survival decreases to approximately 76% and 35%, respectively. Although recent advances in systemic therapies have improved outcomes for patients with advanced melanoma, these treatments are often not curative, and many patients ultimately develop disease progression requiring subsequent lines of therapy. This study aimed to characterize real-world treatment patterns among patients in the USA with advanced cutaneous melanoma who transitioned from first-line (1L) to second-line (2L) systemic therapy. This retrospective, observational study used administrative claims data from a large US managed care database. Adult patients with metastatic melanoma who initiated 1L systemic therapy between January 2023 and December 2025 and subsequently received 2L therapy were included. Claims-based algorithms identified treatment regimens by line of therapy. Sankey diagrams illustrate treatment transitions overall and by BRAF V600 mutation status. Of 1772 patients who met study criteria, 680 (38.4%) were classified as presumed BRAF V600-mutated (BRAFmut) on the basis of treatment exposure, and 1092 (61.6%) were classified as presumed BRAF wild-type (BRAFwt). Immune checkpoint inhibitor (ICI)-based regimens were the most common first-line (1L) therapies (78.5%), while BRAF + MEK inhibitors accounted for 14.4%. In second-line (2L) therapy, sequencing patterns were diverse, with no dominant 2L pathway observed. BRAF + MEK inhibitors were the most frequently used 2L therapy (27.5%). In patients with BRAFmut, targeted therapy predominated in 2L (71.8%), whereas ICI-based regimens remained dominant in patients with BRAFwt (84.9%). 1L therapy was significantly associated with 2L treatment selection (p < 0.001). Treatment distributions differed across index years for both 1L (p = 0.001) and 2L (p = 0.005) therapies. Over time, use of PD-1 monotherapy decreased, while use of nivolumab plus ipilimumab increased; use of BRAF + MEK therapy remained stable. Although treatment practices for advanced melanoma continue to evolve in response to emerging clinical evidence, substantial uncertainty remains regarding optimal treatment sequencing after 1L progression. These findings highlight the need for prospective sequencing studies and more effective therapeutic options following disease progression.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory condition leading to organ dysfunction and death. Primary HLH, driven by genetic mutations that impair immune regulation, predominantly affects children, whereas the secondary (acquired) form is more common in adults. Secondary HLH may be precipitated by various drivers, including medications such as immune checkpoint inhibitors (ICIs). Diagnosing this condition is difficult, as initial signs are often vague and overlap with those of other disorders; consequently, clinicians commonly use the Hemophagocytic Lymphohistiocytosis-2004 (HLH-2004) diagnostic criteria and the H-Score to support the&#xa0;diagnostic evaluation. We report a case of a patient with triple-negative inflammatory breast cancer who developed HLH following anticancer therapy with pembrolizumab. The patient's presentation with fever and cytopenias led to the initial management of neutropenic sepsis. However, following non-response to standard sepsis management, the patient was worked up for HLH. Diagnosis of HLH was supported by histopathological and laboratory findings; the patient fulfilled five HLH-2004 diagnostic criteria and&#xa0;responded to high-dose corticosteroid therapy. This case highlights the importance of considering HLH as a rare immune-related adverse event (irAE) in patients receiving ICIs when presumed diagnosis fails to respond as expected. It further illustrates the value of applying validated diagnostic tools to expedite immunosuppressive therapy.

Purple urine bag syndrome (PUBS) is a rare complication of urinary catheterization in which urine, catheter and collection bag develop a characteristic purple discoloration from bacterial metabolism of dietary tryptophan to indigo and indirubin. It is reported almost exclusively in elderly, chronically catheterized women, with very few reports from sub-Saharan Africa. A 26-year-old para 2+0 woman, six months postpartum and living with HIV (CD4 = 194 cells/&#xb5;L), presented with a two-month history of progressive lower-limb weakness, urinary and fecal incontinence and chronic constipation, with three days of fever and loin pain, having been catheterized three times in the preceding four weeks. She was febrile and paraplegic with a T12 sensory level. Empirical ceftriaxone was started for presumed urosepsis; two days later the urine and bag turned purple. Urine culture grew Escherichia coli at >105 CFU/mL, multidrug-resistant but sensitive to piperacillin/tazobactam. Therapy was escalated and the catheter exchanged; the urine cleared within 24&#xa0;hours with symptomatic improvement. MRI showed a lytic T10/T11 lesion with cord compression and hepatic and pulmonary nodules consistent with metastatic disease; tumor markers were within normal limits, narrowing but not excluding the primary. Recognized PUBS risk factors include prolonged catheterization, female sex, neurogenic bladder, immobility, chronic constipation and renal disease, occurring mostly in elderly women. Our patient was young but had several of these factors, plus multidrug-resistant bacteriuria and HIV-related immunosuppression that may have increased her susceptibility to infection. Cumulative risk-factor burden, rather than age alone, appears to drive the syndrome; empirical ceftriaxone failed, reflecting rising regional cephalosporin resistance. PUBS is a visible indicator of catheter-associated urinary tract infection that can occur outside the typical elderly demographic when risk factors converge and should prompt urgent culture, catheter exchange and culture-directed antibiotics to prevent progression to urosepsis: to our knowledge, the first reported case from Uganda.

AL amyloidosis is characterized by extracellular deposition of immunoglobulin light-chain fibrils, frequently leading to kidney involvement and progressive organ dysfunction. We report a case of kidney AL amyloidosis secondary to multiple myeloma in which daratumumab-based chemotherapy combined with autologous peripheral blood stem cell transplantation resulted in marked improvement, as confirmed by sequential kidney biopsy. The initial biopsy revealed vascular-dominant amyloid deposition, whereas the second biopsy obtained 2&#xa0;years later demonstrated a marked reduction in amyloid burden, particularly within the vascular compartments. This histopathological improvement corresponded with hematologic remission and stabilization of kidney function. The observed reduction in tissue amyloid deposits was presumed to result from suppression of amyloidogenic light chains, leading to inhibition of new fibril formation and subsequent tissue remodeling. Our findings provide direct pathological evidence that daratumumab-based combination therapy, through immune-mediated plasma cell depletion, may indirectly promote the regression of amyloid deposits and contribute to functional recovery.

An older woman in her late 70s was referred for swallowing assessment because of recurrent aspiration pneumonia, weight loss, low body mass index, reduced handgrip strength, and slow gait speed, initially suggesting sarcopenic dysphagia. However, flexible endoscopic evaluation of swallowing and videofluoroscopic swallowing study demonstrated marked delay in swallow initiation, impaired airway protective reflexes, and reduced pharyngeal sensation despite the absence of substantial pharyngeal residue and relatively preserved upper esophageal sphincter opening. Careful reassessment of the videofluoroscopic study revealed abnormal craniovertebral alignment. Subsequent computed tomography demonstrated atlantoaxial dislocation with superior migration of the odontoid process, and magnetic resonance imaging confirmed compression of the medulla oblongata. This case highlights the importance of avoiding oversimplified attribution of dysphagia to sarcopenia and of reconsidering alternative neural or structural mechanisms when observed swallowing physiology is discordant with the presumed diagnosis.

Osteomyelitis of the pubic symphysis is a rare entity, affecting less than 1% of all osteomyelitis cases. It most frequently occurs in individuals with predisposing conditions, including states of immunosuppression, a history of pelvic or urogenital surgery, and intravenous drug use. In patients with rheumatoid arthritis (RA), the diagnosis can be substantially delayed because clinical manifestations may mimic or overlap with those of inflammatory joint disease. We describe a case of presumed culture-negative osteomyelitis of the pubic symphysis in a patient with RA, emphasizing the diagnostic challenges and therapeutic considerations in this complex clinical setting. A woman in her late 60s with long-standing seropositive RA, managed with methotrexate and prednisolone, and with comorbid type 2 diabetes mellitus, hypertension, and osteoporosis, presented with a two&#x2011;month history of progressively worsening right groin pain refractory to analgesic therapy, leading to significant functional limitation and gait impairment. On admission, she was afebrile with hemodynamically stable vital signs. Physical examination revealed suprapubic tenderness and a reduced range of motion of the right hip. Laboratory investigations showed leukocytosis (14.2&#x2009;&#xd7;&#x2009;10&#x2079;/L, 91% neutrophils), markedly elevated C&#x2011;reactive protein (149&#x2009;mg/L), and an increased erythrocyte sedimentation rate (133&#x2009;mm/h). Blood cultures remained sterile, whereas urine culture grew methicillin&#x2011;sensitive Staphylococcus aureus (MSSA). Serological testing for brucellosis and a tuberculin skin test were both negative. Contrast&#x2011;enhanced computed tomography (CT) of the pelvis demonstrated an abscess involving the pubic symphysis associated with reactive osteitis. Culture of aspirated abscess material was sterile, and histopathological examination of the biopsy specimen showed nonspecific inflammatory changes without granulomatous inflammation. Empirical antimicrobial therapy with intravenous cefazolin and ciprofloxacin was administered for 30&#x2009;days, followed by oral ciprofloxacin and doxycycline for an additional two months. The patient achieved complete clinical and laboratory resolution without the need for surgical intervention. Follow&#x2011;up CT imaging confirmed resolution of the abscess, with residual diastasis of the pubic symphysis. Pubic symphysis osteomyelitis should be included in the differential diagnosis of atypical pelvic pain in immunosuppressed patients with RA. Ongoing immunosuppressive therapy may obscure or attenuate systemic manifestations of infection, thereby contributing to delayed diagnosis. Early utilization of cross-sectional imaging modalities and the administration of prolonged, targeted antimicrobial therapy are critical to achieving favourable clinical outcomes.

The dentate gyrus (DG) is thought to play a key role in the formation of dissociable memory representations for similar contexts. Neurons in the DG receive highly processed spatial and nonspatial sensory information from the medial and lateral entorhinal cortices, respectively. Changes in spatially tuned firing patterns of DG place cells occur after spatial changes to an environment, but the degree to which DG place cells respond to ethologically relevant nonspatial stimuli is largely unknown. Spatial and nonspatial information is thought to be transmitted to the DG during discrete local field potential events called dentate spikes. Here, we tested the extent to which different spatial and nonspatial stimuli modulate place cell firing patterns and dentate spike dynamics. We performed extracellular recordings of DG place cells and local field potentials in rats of both sexes exploring a familiar spatial environment, in which social stimuli and nonsocial odors of varying ethological relevance were presented, and a novel spatial environment. As expected, DG place cells exhibited different firing patterns between familiar and novel environments. Significant changes in firing were not observed, however, with any of the nonspatial stimuli. Surprisingly, the occurrence of dentate spikes associated with lateral entorhinal cortex input increased during exploration of ethologically relevant stimuli, and this increase was greater for social stimuli. Altogether, these results suggest that the DG preferentially responds to social stimuli at the network level, providing novel insights into how spatial and nonspatial information is processed in the DG.Significance Statement The dentate gyrus (DG) encodes spatial and nonspatial sensory information. Here, we investigated how place cells in the DG respond to changes in spatial and nonspatial cues in familiar and novel environments in rats. We found that DG place cell firing patterns significantly changed in a novel spatial environment but did not significantly change when nonspatial stimuli were presented in a familiar environment. Conversely, discrete dentate spike events reflecting presumed nonspatial inputs from the lateral entorhinal cortex increased during investigation of ethologically relevant nonspatial stimuli. These findings suggest novel mechanisms of nonspatial information processing in the DG.

Glomangiopericytoma (GPC) is a rare sinonasal mesenchymal neoplasm with distinctive morphologic and molecular features, most commonly arising in the nasal cavity and paranasal sinuses. Occurrence in the nasopharynx is exceptionally uncommon and may create a substantial diagnostic challenge, particularly in long-term survivors of nasopharyngeal carcinoma (NPC) after radiotherapy, in whom a newly detected nasopharyngeal mass is often clinically presumed to represent recurrent carcinoma.In this setting, diagnosis should rest on the combined assessment of growth architecture, cytologic blandness, and a targeted exclusionary immunohistochemical panel rather than on clinical history, imaging appearance, or any single marker alone. A man in his early seventies, previously treated with chemoradiotherapy for NPC approximately 30 years earlier, presented with a 15-day history of right-sided ptosis and headache. Nasoendoscopy demonstrated a smooth, highly vascular mass arising from the right posterior nasopharyngeal wall. Magnetic resonance imaging revealed a skull-base lesion extending toward the cavernous sinus, with radiologically suspicious cervical lymphadenopathy that was not pathologically sampled, raising concern for recurrent malignancy. Endoscopic biopsy showed a spindle-cell neoplasm composed of bland oval-to-spindle cells arranged in storiform and whorled patterns around branching thin-walled vessels. Immunohistochemically, the tumor cells showed diffuse vimentin expression, focal-to-patchy nuclear &#x3b2;-catenin positivity, scattered Cyclin D1 nuclear positivity, and partial Bcl-2 positivity, whereas STAT6, CD34, cytokeratin, S100, and SMA were negative. These combined morphologic and immunophenotypic findings, although not molecularly confirmed, supported the diagnosis of GPC and argued against recurrent NPC, solitary fibrous tumor, and other spindle-cell neoplasms. Because of extensive skull-base and cavernous-sinus involvement, the lesion was considered unresectable. Empirical palliative docetaxel-cisplatin treatment produced transient symptomatic improvement but was followed by fatal neutropenic sepsis. This case highlights that a vascular submucosal nasopharyngeal mass arising decades after radiotherapy is not necessarily recurrent NPC. In this setting, careful histomorphologic evaluation combined with a practical immunohistochemical panel, particularly focal-to-patchy nuclear &#x3b2;-catenin positivity with STAT6, CD34, and cytokeratin negativity, can support a diagnosis of GPC and help avoid misclassification as recurrent carcinoma or other spindle-cell neoplasms in a previously irradiated field. Because CTNNB1 testing was not performed, the diagnosis should be interpreted as morphologically and immunohistochemically supported rather than molecularly confirmed.

Diabetic papillopathy (DP), a rare complication of diabetes mellitus, involves benign changes in the optic nerve head due to metabolic stress or immune dysfunction. This report describes a middle-aged male patient with type 2 diabetes mellitus for 1 year, presenting with painless, progressive blurring of vision in his right eye for 2&#x2009;weeks. His best corrected visual acuity was 6/18 in the right eye and 6/6 in the left. Examination revealed a sluggish pupillary reaction, grade 1 relative afferent pupillary defect, optic disc hyperaemia, obscured margins and venous tortuosity in the right eye. He was treated for presumed optic neuritis (ON) with intravenous and oral corticosteroids. However, Vision worsened during the period of corticosteroid treatment. Although a temporal association was observed, a causal relationship between corticosteroid therapy and worsening of DP cannot be definitively established from a single case. Anti-neuromyelitis optica antibody was negative while anti-myelin oligodendrocyte antibody was weakly positive. MRI showed optic nerve thickening without demyelination or raised intracranial pressure. After being diagnosed with DP, corticosteroids were tapered and the treatment focus shifted to strict glycaemic control. Disc oedema can be the common feature in both with microvascular occlusion in DP and inflammation in ON as the underlying cause. This case emphasises the importance of distinguishing DP from other optic neuropathies, as their treatments are vastly different and diametrically opposite.

Background and Clinical Significance: Tumors of the lacrimal drainage system are rare but clinically important diagnostic pitfalls because they may mimic benign lacrimal drainage obstruction, chronic dacryocystitis, or sinonasal disease. Pleomorphic adenoma (PA) in this region is exceptionally rare, and delayed recognition may allow progressive extension into adjacent structures. Case Presentation: A 51-year-old woman presented with left nasal obstruction 16 years after external dacryocystorhinostomy for presumed lacrimal drainage obstruction. Examination showed a firm left lacrimal sac mass, proptosis, mild ocular motility limitation, and an intranasal mass. Computed tomography and magnetic resonance imaging showed a large lesion centered in the lacrimal sac region and extending into the nasolacrimal duct, nasal cavity, and maxillary sinus, with orbital displacement. Preoperative biopsy showed epithelial neoplastic tissue without definitive malignant features, but low-grade epithelial malignancy could not be excluded. Complete en bloc excision and medial/inferior orbital wall reconstruction with an autologous calvarial outer table bone graft were performed. The tumor measured 55 &#xd7; 35 &#xd7; 25 mm. Final histopathology confirmed PA without malignant transformation. At 2 years postoperatively, there was no recurrence, and proptosis and ocular motility limitation had improved. Conclusions: This case illustrates two diagnostic pitfalls: an underlying tumor may masquerade as lacrimal drainage obstruction, whereas a large benign PA may clinically and radiologically mimic malignancy. Long-standing or atypical unilateral lacrimal symptoms should prompt consideration of tumors and selected use of imaging and tissue diagnosis before lacrimal drainage surgery.

Mycobacterium marinum is a slow-growing nontuberculous mycobacterium, most commonly causing cutaneous infection after prolonged or repeated exposure to contaminated aquatic environments. Diagnosis is frequently delayed because of its indolent course, nonspecific clinical features, and frequent misattribution to more common dermatologic conditions. We report the case of a 51-year-old immunocompromised woman who developed a progressive ulcerative lesion on the right wrist after a presumed spider bite following a farm visit. Despite multiple emergency department encounters and empiric antibacterial therapy, the lesion failed to improve. Acid-fast bacilli culture from a wound specimen ultimately grew M. marinum several weeks after initial presentation. Subsequent history revealed a previously undisclosed history of exposure to a home aquarium. Management was complicated by impaired oral antimicrobial absorption following prior bariatric surgery and incomplete clinical response to initial therapy, necessitating prolonged outpatient parenteral antimicrobial treatment, with eventual clinical resolution. This case underscores the impact of diagnostic anchoring bias, highlights the importance of thorough environmental exposure assessment beyond classic aquatic settings, and emphasizes early consideration of nontuberculous mycobacterial infection in chronic, nonhealing cutaneous lesions.

Congenital coronary artery anomalies are uncommon but clinically significant conditions associated with myocardial ischemia, malignant ventricular arrhythmias, and sudden cardiac death, particularly in young individuals. Among these anomalies, anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA) is exceptionally rare, with a reported prevalence of approximately 0.002%. Although ARCAPA may remain clinically silent for many years due to collateral circulation from the left coronary system, it carries a persistent risk of myocardial ischemia caused by a coronary steal phenomenon and may result in sudden cardiac death. We report the case of a 19-year-old Somali male with no prior medical history who presented with a several-month history of recurrent syncope occurring both at rest and during exertion, without preceding chest pain, palpitations, dyspnea, seizure-like activity, or prodromal symptoms. He presented following a prolonged syncopal episode and was found to be hemodynamically unstable, with a blood pressure of 86/54 mmHg and sinus tachycardia. Initial laboratory investigations, including complete blood count, renal function, serum electrolytes, coagulation profile, and cardiac biomarkers, were within normal limits. Electrocardiography demonstrated diffuse ST-segment depression in the inferolateral leads with reciprocal ST-segment elevation in lead aVR, raising concern for global subendocardial ischemia. Transthoracic echocardiography revealed preserved left ventricular systolic function, with an ejection fraction of 65%, a mildly dilated main pulmonary artery, and mild pulmonary regurgitation. Due to the unavailability of coronary computed tomography angiography, urgent invasive coronary angiography was performed approximately 4 hours after presentation. Angiography revealed anomalous origin of the right coronary artery from the pulmonary artery with retrograde flow into the pulmonary trunk, consistent with a significant coronary steal phenomenon. No obstructive coronary artery disease was identified. Approximately 30 minutes after angiography, the patient developed sudden hemodynamic collapse and progressed to cardiac arrest. Despite prolonged advanced cardiopulmonary resuscitation, return of spontaneous circulation was not achieved. The presumed cause of death was malignant ventricular arrhythmia secondary to myocardial ischemia related to ARCAPA; however, the exact mechanism could not be definitively established. This case highlights the potential for rapid fatal deterioration in ARCAPA despite preserved ventricular systolic function. Recurrent syncope and ischemic electrocardiographic abnormalities should be recognized as high-risk features. The electrocardiographic pattern observed may reflect diffuse myocardial ischemia due to coronary steal rather than atherosclerotic coronary artery disease. ARCAPA should be considered in young patients presenting with unexplained recurrent syncope and high-risk electrocardiographic findings. Early recognition, appropriate use of multimodality imaging, close monitoring, and prompt surgical referral are essential to prevent catastrophic outcomes.