Acquired Angioedema Associated with Lymphoproliferative Disorders.

Introduction: Acquired angioedema due to C1 esterase inhibitor deficiency (C1INH-AAE) is most associated with lymphoproliferative disorders (LPDs), particularly low-grade B-cell subtypes. The condition remains under-recognized with long diagnostic delays due to various challenges including a lack of awareness of the condition. Case Presentation: We discuss 4 cases of C1INH-AAE associated with low-grade B-cell LPDs, including various diagnostic and management challenges. As our cases illustrate, constitutional symptoms or overt manifestations of LPD at diagnosis are often absent. Hence, a comprehensive multimodal approach to screening for an underlying B-LPD is important when a diagnosis of acquired angioedema is made. Levels of complement C4, C1q, and C1INH are useful for diagnosing C1INH-AAE and for monitoring disease activity. Changes in these parameters may also indicate relapse of the underlying hematological malignancy. Treating the underlying disorder is important as this commonly leads to clinical improvement with decreased episodes of angioedema and normalization of complement studies. Conclusion: Awareness of C1INH-AAE can lead to an early diagnosis of hematological malignancies. The absence of constitutional symptoms emphasizes the need for a comprehensive multimodal approach to screening for LPD in C1INH-AAE. C4, C1INH level, and function are useful for monitoring disease activity.

Antibiotic prophylaxis in immunosuppressed patients - Missed opportunities from trimethoprim-sulfamethoxazole allergy label.

Trimethoprim-sulfamethoxazole (TMP-SMX) is a broad spectrum antibiotic in use for more than 50 years. It has an important indication as first line agent in the prophylaxis of opportunistic infections, particularly Pneumocystis jirovecii pneumonia (PJP), in immunosuppressed patients. For those who have a history of allergy or severe intolerance to TMP-SMX, pentamidine, dapsone or atovaquone may be substituted; however there is evidence that TMP-SMX offers superior coverage for PJP, toxoplasmosis, and nocardiosis. Compared to pentamidine, it has the added benefit of cost-effectiveness and self-administration as opposed to required hospital attendance for administration. Many patients who report a history of allergy or adverse reaction to TMP-SMX (or "sulfur allergy") will be found not to be allergic; and even those who are allergic may be able to be desensitized. The evaluation and, where appropriate, removal of TMP-SMX allergy label enables the use of TMP-SMX for prophylaxis against opportunistic infections. This is a cost-effective intervention to optimize antimicrobial prescribing and reduce the risk of opportunistic infections in immunosuppressed patients.

Lenalidomide Desensitization for Delayed Cutaneous Reaction: A Case Series and Review of the Literature.

BACKGROUND: Lenalidomide is commonly used for treatment of multiple myeloma (MM) as well as other hematological disorders. Cutaneous adverse reactions occur frequently and withholding lenalidomide treatment may have implications for prognosis. OBJECTIVE: To evaluate the role of lenalidomide desensitization in patients with cutaneous adverse reactions. METHODS: A retrospective review of patients referred for lenalidomide desensitization between May 2019 and May 2022 at a tertiary hospital. All patients underwent a 6-week outpatient desensitization with premedication. RESULTS: There were 12 patients: 10 males and 2 females with a median age of 65 years. All had MM with autologous stem cell transplantation and lenalidomide 10 mg daily added for maintenance therapy. Most patients (n = 8) had a generalized maculopapular exanthem with or without pruritus. All patients had delayed cutaneous reactions; the median time to onset was 14 days (range 2-28 d). Six patients tolerated desensitization: 5 on the first attempt and 1 after 3 attempts and supplementary oral prednisolone. Four patients underwent multiple (≤3) attempts at desensitization owing to breakthrough symptoms. In patients who failed desensitization, recurrence of symptoms occurred variably, either early (within days), within weeks, or delayed by more than 1 month. CONCLUSIONS: Lenalidomide desensitization is worthwhile and allows continuation of treatment. In our MM cohort, lenalidomide desensitization was successful in only 50% of cases, including some cases in whom ongoing symptoms were mitigated by cotreatment with antihistamine.

Retrospective single-centre analysis of diagnostic approach to adult-onset haemophagocytic lymphohistiocytosis.

BACKGROUND: Haemophagocytic lymphohistiocytosis (HLH) is a rare disorder with a poor prognosis characterised by substantial immune activation leading to end-organ failure. In childhood, genetic defects that impair cytotoxic function of natural killer cells and T cells. (HLH) are often identified. In adults, clinical manifestations are similar to those observed in children but the aetiology is often unclear. AIMS: To evaluate whether poor prognosis for adult HLH is in part due to lack of awareness of the disorder, which results in incomplete investigation and failure to implement timely treatment. METHODS: We performed a retrospective case series of adult-onset HLH in a tertiary hospital in Australia. We evaluated clinical characteristics, treatment and outcome, and related these to application of standard diagnostic criteria for HLH. RESULTS: In our centre, incomplete assessment of HLH criteria was common. Serum ferritin was the criterion most commonly assessed. Hyperferritinaemia ≥10 000 µg/L was highly sensitive in detecting patients with adult-onset HLH; however, the majority of patients who had hyperferritinaemia ≥10 000 µg/L did not have adult-onset HLH. CONCLUSION: The present study highlights the importance of comprehensive application of diagnostic criteria to improve accuracy and timelines of the diagnosis of adult onset HLH.

The significance of ANCA positivity in patients with inflammatory bowel disease.

Traditionally anti-neutrophil cytoplasmic antibodies (ANCA) are used to subtype patients with inflammatory bowel disease (IBD) and to predict primary sclerosing cholangitis (PSC). The clinical utility of this testing in the Australian context is not known. Our retrospective, cross-sectional study looked at the results of ANCA testing performed during routine clinical review and aimed to retrospectively review (1) the distribution of different ANCA subtypes for IBD patients, (2) the temporal change of ANCA status, and (3) the predictive value of ANCA for PSC. Sixty-four IBD patients attending our hospital gastroenterology clinic between 2012 and 2016 had at least one ANCA test requested. Surprisingly, >80% of the IBD patients in our cohort who underwent ANCA testing had a positive ANCA result and a significant proportion had positive PR3 antibodies. However, no specific ANCA pattern predicted a specific IBD subtype or clinical course. Pairing ANCA and anti-Saccharomyces cerevisiae (ASCA) did not add value in subtyping IBD for these patients. Our study suggests that there is little value in ordering an ANCA for patients with IBD.

Microscopic evidence for the dissociation of water molecules on cleaved GaN(11[combining macron]00).

The dissociation of water molecules absorbed on a cleaved non-polar GaN(11[combining macron]00) surface was studied primarily with synchrotron-based photoemission spectra and density-functional-theory calculations. The adsorbed water molecules are spontaneously dissociated into hydrogen atoms and hydroxyl groups at either 300 or 130 K, which implies a negligible activation energy (<11 meV) for the dissociation. The produced H and OH were bound to the surface nitrogen and gallium on GaN(11[combining macron]00) respectively. These results highlight the promising applications of the non-polar GaN(11[combining macron]00) surface in water dissociation and hydrogen generation.

Controlling bottom-up rapid growth of single crystalline gallium nitride nanowires on silicon.

We report single crystalline gallium nitride nanowire growth from Ni and Ni-Au catalysts on silicon using hydride vapor phase epitaxy. The growth takes place rapidly; efficiency in time is higher than the conventional nanowire growth in metal-organic chemical vapor deposition and thin film growth in molecular beam epitaxy. The effects of V/III ratio and carrier gas flow on growth are discussed regarding surface polarity and sticking coefficient of molecules. The nanowires of gallium nitride exhibit excellent crystallinity with smooth and straight morphology and uniform orientation. The growth mechanism follows self-assembly from both catalysts, where Au acts as a protection from etching during growth enabling the growth of ultra-long nanowires. The photoluminescence of such nanowires are adjustable by tuning the growth parameters to achieve blue emission. The practical range of parameters for mass production of such high crystal quality and uniformity of nanowires is suggested.

Refractory focal motor seizures controlled with intramuscular botulinum toxin.

Patients with recurrent focal motor seizures present a management dilemma, as anti-convulsants are often ineffective, and resective surgery poses a high risk of motor deficit. We describe three patients with recurrent focal motor seizures that remained refractory despite numerous anti-convulsant trials. All patients showed either hyperperfusion on Single-Photon Emission Computerised Tomography (SPECT) or hypermetabolism on Positron Emission Tomography (PET) in primary motor cortex during periods of sustained jerking, although EEG abnormalities were uncommon. After botulinum toxin (BoT) injection there was a rapid and dramatic reduction in seizure frequency in all patients despite minimal limb weakness. Seizure freedom persisted for 3-6 months following treatment in the injected area. Repeat BoT injections following seizure recurrence were again efficacious in one case. Combining data from our cases with those previously reported, it appears that BoT may be a useful therapeutic tool for recurrent focal motor seizures. We hypothesise that the toxin disrupts or down-regulates an epileptic circuit between motor cortex and muscle, in which volleys of information from muscle spindles have been perpetuating seizure discharges in the cortex.

Hypopharyngeal large cell neuroendocrine carcinoma.

Neuroendocrine carcinoma (NEC) of the head and neck is rare. We report a case of a 56-year-old man with a 6-week history of dysphagia, a neck mass and weight loss. He was diagnosed with a hypopharyngeal large cell NEC (LCNEC) with metastases to multiple sites. He received two cycles of cisplatin and etoposide. Subsequent restaging scan revealed progressive disease. The patient declined further chemotherapy and died shortly after. This is the third case of LCNEC of hypopharynx reported in the English literature and the first to progress on platinum-based chemotherapy. Although LCNEC of the head and neck is still classified as an atypical carcinoid, there is increasing evidence it is a distinct clinicohistopathological entity that carries an especially poor prognosis. Currently, there is a paucity of data to guide treatment of this rare malignancy.

Single-institution Experience of Unrelated Cord Blood Transplantation for Primary Immunodeficiency.

Pediatric patients with primary immunodeficiencies (PID) constitute life-threatening medical emergencies. In the absence of an HLA-identical hematopoietic stem cell donor, unrelated donor cord blood transplantation (CBT) is another treatment option. There are little data regarding the outcome of unrelated CBT for PID in Taiwan. We report the results of CBT performed in 8 patients with PID between 2004 and 2013 at Chang Gung Memorial Hospital. The cases included severe combined immunodeficiency (n=4), chronic granulomatous disease (n=2), Wiskott-Aldrich syndrome (n=1), and T-cell immunodeficiency (n=1). Median follow-up time was 73 months. Most UCB recipients received a myeloablative conditioning regimen. There were 7 boys and 1 girl with a median age of 2.5 months at diagnosis (range, antenatal to 17 mo). Median age at transplant was 5.5 months (range, 2 to 74 mo). All but 1 patients engrafted at a median time of 14 days. One developed significant grade III graft-versus-host disease after transplant. Our data show that unrelated CBT in PID is possible. However, no definite conclusions can be drawn from this small number of patients, and more studies are needed to further investigate and confirm these findings.

Post-mortem CT findings in a case of necrotizing cellulitis of the floor of the mouth (Ludwig angina).

Ludwig angina is a rare but potentially lethal infection of the submandibular space that can cause significant upper airway obstruction. We report a case of undiagnosed Ludwig angina that progressed rapidly to death. Ludwig angina was suspected after post-mortem computed tomography (PMCT) found swollen mylohyoid muscle with stranding in subcutaneous fat, thickening of deep fascia, and local lymphadenopathy. Subsequently, an autopsy revealed woody induration of the submental region and liquefactive necrosis of the mylohyoid muscle, confirming the diagnosis. It is likely that the dental abscess identified on PMCT was the source of infection. Multiple invasive medical procedures were performed on the subject by the ambulance crew prior to his death. PMCT assisted further in determining procedural success.

The effect of free-standing GaN substrate on carrier localization in ultraviolet InGaN light-emitting diodes.

In this study, we have grown 380-nm ultraviolet light-emitting diodes (UV-LEDs) based on InGaN/AlInGaN multiple quantum well (MQW) structures on free-standing GaN (FS-GaN) substrate by atmospheric pressure metal-organic chemical vapor deposition (AP-MOCVD), and investigated the relationship between carrier localization degree and FS-GaN. The micro-Raman shift peak mapping image shows low standard deviation (STD), indicating that the UV-LED epi-wafer of low curvature and MQWs of weak quantum-confined Stark effect (QCSE) were grown. High-resolution X-ray diffraction (HRXRD) analyses demonstrated high-order satellite peaks and clear fringes between them for the UV-LEDs grown on the FS-GaN substrate, from which the interface roughness (IRN) was estimated. The temperature-dependent photoluminescence (PL) measurement confirmed that the UV-LEDs grown on the FS-GaN substrate exhibited better carrier confinement. Besides, the high-resolution transmission electron microscopy (HRTEM) and energy-dispersive spectrometer (EDS) mapping images verified that the UV-LEDs on FS-GaN have fairly uniform distribution of indium and more ordered InGaN/AlInGaN MQW structure. Clearly, the FS-GaN can not only improve the light output power but also reduce the efficiency droop phenomenon at high injection current. Based on the results mentioned above, the FS-GaN can offer UV-LEDs based on InGaN/AlInGaN MQW structures with benefits, such as high crystal quality and small carrier localization degree, compared with the UV-LEDs on sapphire.

Clinical factors are significant predictors of outcome post intra-arterial therapy for acute ischaemic stroke: a review.

Intra-arterial therapy (IAT) provides superior recanalisation rates, approaching 80% for the current generation of endovascular devices. Furthermore, IAT may allow for an extended therapeutic window beyond that which is permissible for intravenous thrombolysis. However, the improved recanalisation rates are not matched by concordant clinical outcomes, leading to an invigorated search for predictors of clinical outcome. There is emerging evidence that younger age, mild-moderate stroke, and shorter vessel occlusion time are associated with better clinical outcome after IAT. This review aims to critically appraise current evidence that may inform changes in the selective inclusion of clinical factors in the future design and trial of IAT.

Early transplantation of unrelated cord blood in a two-month-old infant with Wiskott-Aldrich syndrome.

This report exemplified a success of unrelated CBT in a two-month-old boy with Wiskott-Aldrich Syndrome. Umbilical cord blood was chosen as the stem-cell source because of its immediate availability and reduced tendency to cause GVHD. The conditioning regimen was cyclophosphamide, busulfan, and antithymocyte globulin. GVHD prophylaxis consisted of cyclosporin and methylprednisolone. The patient received an HLA 1-locus-mismatched cord blood unit, and the total number of infused nucleated cells was 11.14 x 10(7)/kg. Neutrophil engraftment was achieved on day +11, and a platelet count greater than 50 x 10(9)/L was achieved on day +71. He is currently alive and doing well at nine months post-transplant and free of any bleeding episodes. This case suggests that unrelated donor CBT may be safe and technically feasible, even in early infancy, when an appropriately matched related or unrelated donor is unavailable.

Successful unrelated mismatched cord blood transplantation in a child with malignant infantile osteopetrosis.

Allogeneic hematopoietic stem cell transplantation represents the only curative option for malignant infantile osteopetrosis (MIOP), a rare disease of infants and young children, characterized by excessive accumulation of mineralized bone and abnormal hematopoiesis. We report a case of successful engraftment and stable full-donor chimerism in a patient with MIOP who underwent unrelated donor cord blood transplantation (CBT). The donor was 2-loci human leukocyte antigen (HLA)-mismatch. After a conditioning regimen based on the combination of busulfan, cyclophosphamide, total body irradiation, and antithymocyte globulin, the patient received a dose of 3.85 x 10(7)/kg of nucleated cells. Neutrophil and platelet engraftment had been achieved by day +33 and +82, respectively, and the patient was discharged home on day +89. A successful engraftment of donor hematopoiesis was demonstrated and the child experienced grade II acute graft-vs.-host disease (GVHD) involving the skin only. A remarkable but non-progressive decrease in lumbar spine bone mineral density was observed in the first nine months post-transplant. This case suggests that unrelated donor CBT may be a feasible option in case of unavailability of a fully HLA-matched related or unrelated donor.