Common Long-term Complication Research Articles

Targeting CDC42 reduces skeletal degeneration after hematopoietic stem cell transplantation

AbstractOsteopenia and osteoporosis are common long-term complications of the cytotoxic conditioning regimen for hematopoietic stem cell transplantation (HSCT). We examined mesenchymal stem and progenitor cells (MSPCs), which include skeletal progenitors, from mice undergoing HSCT. Such MSPCs showed reduced CFU-F frequency, increased DNA damage, and enhanced occurrence of cellular senescence, whereas there was a reduced bone volume in animals that underwent HSCT. This reduced MSPC function correlated with elevated activation of the small Rho guanosine triphosphate hydrolase Cdc42, disorganized F-actin distribution, mitochondrial abnormalities, and impaired mitophagy in MSPCs. Changes and defects similar to those in mice were also observed in MSPCs from humans undergoing HSCT. A pharmacological treatment that attenuated the elevated activation of CDC42 restored F-actin fiber alignment, mitochondrial function, and mitophagy in MSPCs in vitro. Finally, targeting CDC42 activity in vivo in animals undergoing transplants improved MSPC quality to increase both bone volume and trabecular bone thickness. Our study shows that attenuation of CDC42 activity is sufficient to attenuate reduced function of MSPCs in a BM transplant setting.

Unraveling the Complexities of Uretero-Enteric Strictures: A Modern Review.

The purpose of this review article is to provide a contemporary overview of benign uretero-enteric anastomotic stricture (UAS) management and outcomes. In this article, we will review the most recent studies investigating UAS and evaluate etiology, potential risk factors, presentation, diagnosis, and management options, along with personal insight gained from our experience with managing this challenging reconstructive complication. Benign UAS is a relatively common long-term complication of intestinal urinary diversion, affecting approximately 1 in 10 patients. It is thought to be caused by ureteral tissue ischemia and fibrosis at the anastomotic site. Risk factors appear to include any that increase the likelihood of leak or ischemia; it is not clear if anastomotic approach impacts risk for stricture as well. Management options are varied and include endourologic, open, and robotic approaches. Endoscopic approaches may be less morbid but are considerably less effective than reconstruction performed after a period of ureteral rest.

Challenges of Hip and Knee Arthroplasty in Patients With Osteopetrosis.

Osteopetrosis is a rare metabolic bone disease, characterized by dysfunction of osteoclasts, resulting in increased bone density and brittleness leading to pathological fractures and bone deformities. Hip and knee osteoarthritis (OA) are common long-term complications in patients with osteopetrosis. Joint arthroplasty surgery remains an effective and recommended treatment for these patients with an end-stage OA because it provides favorable outcomes. However, in osteopetrosis, joint arthroplasty surgery carries an increased risk of complications, and specific preoperative and perioperative considerations are required to deal with the technical challenges related to the disease. The aim of this article was to review some of the key aspects of osteopetrosis, provide technical recommendations, and answer clinically relevant questions related to hip and knee arthroplasty surgery.

Pharmacological characterization of the antidiabetic drug metformin in atherosclerosis inhibition: A comprehensive insight.

Atherosclerosis (AS) is a progressive disease that interferes with blood flow, leading to cardiovascular complications such as hypertension, ischemic heart disease, ischemic stroke, and vascular ischemia. The progression of AS is correlated with inflammation, oxidative stress, and endothelial dysfunction. Various signaling pathways, like nuclear erythroid-related factor 2 (Nrf2) and Kruppel-like factor 2 (KLF2), are involved in the pathogenesis of AS. Nrf2 and KLF2 have anti-inflammatory and antioxidant properties. Thus, activation of these pathways may reduce the development of AS. Metformin, an insulin-sensitizing drug used in the management of type 2 diabetes mellitus (T2DM), increases the expression of Nrf2 and KLF2. AS is a common long-term macrovascular complication of T2DM. Thus, metformin, through its pleiotropic anti-inflammatory effect, may attenuate the development and progression of AS. Therefore, this review aims to investigate the possible role of metformin in AS concerning its effect on Nrf2 and KLF2 and inhibition of reactive oxygen species (ROS) formation. In addition to its antidiabetic effect, metformin can reduce cardiovascular morbidities and mortalities compared to other antidiabetic agents, even with similar blood glucose control by the Nrf2/KLF2 pathway activation. In conclusion, metformin is an effective therapeutic strategy against the development and progression of AS, mainly through activation of the KLF2/Nrf2 axis.

Research progress of breast reconstruction in the prevention and treatment of breast cancer-related lymphedema

Advances in the diagnosis and treatment of breast cancer have significantly improved survival rates. Breast cancer-related lymphedema is the most common mid-and long-term complication after breast cancer surgery, which seriously affects the quality of life. Breast reconstruction can not only restore the shape of the breasts after mastectomy, but also reduce the occurrence of lymphedema to some extent. Immediate autologous breast reconstruction combined with lymphatic venous anastomosis (LVA) or vascularized lymph node transfer (VLNT) can effectively prevent lymphedema. Delayed breast reconstruction combined with LVA or VLNT can achieve the dual benefits of restoring the appearance and treating lymphedema at the same time. The autologous tissue flap can function as a bridge to promote lymphatic drainage, thus enhancing the treatment of lymphedema. The advances mentioned above in surgical techniques have provided a basis for decision making in breast reconstruction and the prevention and treatment of breast cancer-related lymphedema, and have also brought hope for improving the quality of life of patients.

Radiation Induced Skin Fibrosis (RISF): Opportunity for Angiotensin II-Dependent Intervention.

Medical procedures, such as radiation therapy, are a vital element in treating many cancers, significantly contributing to improved survival rates. However, a common long-term complication of such exposure is radiation-induced skin fibrosis (RISF), a complex condition that poses substantial physical and psychological challenges. Notably, about 50% of patients undergoing radiation therapy may achieve long-term remission, resulting in a significant number of survivors managing the aftereffects of their treatment. This article delves into the intricate relationship between RISF, reactive oxygen species (ROS), and angiotensin II (Ang II) signaling. It proposes the underlying mechanisms and examines potential treatments for mitigating skin fibrosis. The primary goal is to offer essential insights in order to better care for and improve the quality of life of cancer survivors who face the risk of developing RISF.

How should we treat postherpetic neuralgia?

Postherpetic neuralgia (PHN) is the most common long-term complication of varicella-zoster virus (VZV) reactivation. It is characterized primarily by persistent pain more than 90 days after the illness at the site where the rash was. This pain is sharp, burning, stabbing in nature. Postherpetic neuralgia can lead to a reduced quality of life and negatively affect sleep and daily functioning. The first line of treatment is currently conservative methods, which include anticonvulsants, antidepressants, topical lidocaine, as well as opioids and topical capsaicin. If these measures are ineffective, individually tailored interventional methods may be necessary. Among these, botulinum toxin A injection is the most common. Other methods focus on neuromodulation (which is the alteration of nerve activity through targeted delivery of a stimulus) or blocking individual elements of the nervous system.

Risk Factors of Metabolic Syndrome among Post Living Donor Liver Transplant Egyptian Recipients: Single Center Study

Abstract Background For more than two decades, liver transplantation (LT) has been accepted as the most effective treatment for end-stage liver disease. However, complications following LT significantly affect the quality of life in long-term survival and metabolic syndrome (MS) is now considered to be the most common long-term complication after LT and has been increasing recently with an incidence of 50-60%. Aim of the Study To identify both pre-transplant and post-transplant risk factors which contribute to post-transplant MS (PTMS) among Egyptian recipients. Methods This study is retrospective prospective descriptive in nature. It was held at the Ain Shams Center for Organ Transplant (ASCOT), Ain Shams University Specialized Hospital with a total of 233 adult Egyptian patients who underwent living donor liver transplant (LDLT) from January 2010 through December 2020 were enrolled. Their data were extracted in detail from the medical records and were retrospectively analyzed. Results Our study has demonstrated that the recipient’s age (being old age), the presence of pre-transplant DM, the recipient being overweight prior to transplant, and the etiology of liver disease that served as an indication for liver transplant, especially cryptogenic cirrhosis, as well as the use of immunosuppressive drugs, mTOR inhibitors, in particular, were all strongly associated with the development of PTMS. However, only the presence of pre-transplant DM, the recipient being overweight prior to transplant, and the use of immunosuppressive drugs, mTOR inhibitors (Everolimus/Sirolimus), in particular, were considered independent risk factors of PTMS. Conclusion Early recognition and modification of risk factors of metabolic syndrome -if modifiable- would facilitate prevention of PTMS, which may reduce its prevalence among transplanted patients.

Reconstituted CD74+ NK cells trigger chronic graft versus host disease after allogeneic bone marrow transplantation

Chronic graft-versus-host disease (cGVHD) is the most common long-term complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The patients with pulmonary cGVHD in particular have a very poor prognosis. NK cells are the first reconstituted lymphocyte subset after allo-HSCT; however, the impact of reconstituted NK cells on cGVHD is unclear. Here, we found allogeneic recipients showed obvious pulmonary cGVHD. Surprisingly, deletion of reconstituted NK cells resulted in maximal relief of pulmonary cGVHD. Mechanistically, reconstituted NK cells with donor profiles modulated the pulmonary inflammatory microenvironment to trigger cGVHD. Reconstituted NK cells secreted IFN-γ and TNF-α to induce CXCL10 production by epithelial cells, which recruited macrophages and CD4+ T cells to the lungs. Then macrophages and CD4+ T cells were activated by the inflammatory microenvironment, thereby mediating lung injury. Through assessment of differences in cellular energy, we found that CD74+ NK cells with high mitochondrial potential and pro-inflammatory activity triggered pulmonary cGVHD. Furthermore, targeted elimination of CD74+ NK cells using the anti-CD74 antibody significantly alleviated pulmonary cGVHD but preserved the CD74− NK cells to exert graft-versus-leukemia (GVL) effects. Data from human samples corroborated our findings in mouse models. Collectively, our results reveal that reconstituted CD74+ NK cells trigger pulmonary cGVHD and suggest that administration of CD74 antibody was a potential therapeutic for patients with cGVHD.

Ocular manifestations and long-term complications of rhabdomyosarcoma in children.

The purpose of the study was to describe the ocular manifestations of rhabdomyosarcoma in a large cohort of children. This was a retrospective observational cohort study. The medical records of all pediatric patients with head and neck rhabdomyosarcoma diagnosed between 1997 and 2021 at a tertiary-care pediatric hospital were analyzed. The main outcome measures were the incidence and prognostic role of ocular findings at presentation and long-term ocular complications. There were 77 children with head and neck rhabdomyosarcoma in the study cohort with 38 patients showing ocular manifestations at presentation. Median age at diagnosis was 6.0 years, the median follow-up was 5.7 years and 54.5% were male. At last follow-up, 70.1% had no evidence of progression, 26.0% were deceased, and 2.6% were on palliative treatment. Orbital signs were common (44.2%). The most common ocular findings were proptosis (18.2%), restriction of extraocular motility (28.6%), strabismus/diplopia (22.1%) and ptosis (16.9%). The most common long-term complications were bony hypoplasia/facial asymmetry (40.3%) and keratopathy/dry eye (31.2%). Poor visual acuity (≤20/200) was noted in 13 (16.9%) patients with 5 (6.5%) patients requiring an exenteration. Survival was 100% in primary orbital RMS (p = 0.02), whereas any or a combination of cranial nerve palsies carried a poor prognosis (42% survival, p = 0.008). In our cohort, half of children with rhabdomyosarcoma had ocular manifestations at presentation with about one-third showing orbital tumor involvement. Cranial nerve involvement carried a significantly worse prognosis for survival.

Transplantace jater pro cholestatická onemocnění

Summary: Cholestatic liver diseases are characterized by their progressive nature and limited conservative treatment options. Liver transplantation is the only effective method of treatment for the terminal stage. Before the era of liver transplantation, patients with cholestatic disease had a significantly reduced life expectancy. Liver transplantation is now indicated not only for patients with chronic liver failure or hepatobiliary malignancy, but also for those with reduced quality of life from cholestatic symptoms. Post-transplant care is particularly specific because of the presence of immune-associated diseases, such as inflammatory bowel disease in patients with primary sclerosing cholangitis. Recurrence of the underlying disease in the liver graft is a common long-term complication that can negatively affect graft survival and overall life expectancy. Despite the risk of recurrence, the long-term outcomes of liver transplantation for cholestatic disease are excellent, achieving longer survival compared to other transplant recipients. Key words: liver transplantation – primary sclerosing cholangitis – primary biliary cholangitis – secondary sclerosing cholangitis – liver sarcoidosis

Single-Center Experience of Pediatric Cystic Kidney Disease and Literature Review.

Pediatric cystic kidney disease (CyKD) includes conditions characterized by renal cysts. Despite extensive research in this field, there are no reliable genetics or other biomarkers to estimate the phenotypic consequences. Therefore, CyKD in children heavily relies on clinical and diagnostic testing to predict the long-term outcomes. A retrospective study aimed to provide a concise overview of this condition and analyze real-life data from a single-center pediatric CyKD cohort followed during a 12-year period. Medical records were reviewed for extensive clinical, laboratory, and radiological data, treatment approaches, and long-term outcomes. During the study period, 112 patients received a diagnosis of pediatric CyKD. Male patients were more involved than female (1:0.93). Fifty-six patients had a multicystic dysplastic kidney; twenty-one of them had an autosomal dominant disorder; fifteen had an isolated renal cyst; ten had been diagnosed with autosomal recessive polycystic kidney disease; three had the tuberous sclerosis complex; two patients each had Bardet-Biedl, Joubert syndrome, and nephronophthisis; and one had been diagnosed with the trisomy 13 condition. Genetic testing was performed in 17.9% of the patients, revealing disease-causing mutations in three-quarters (75.0%) of the tested patients. The most commonly presenting symptoms were abdominal distension (21.4%), abdominal pain (15.2%), and oligohydramnios (12.5%). Recurrent urinary tract infections (UTI) were documented in one-quarter of the patients, while 20.5% of them developed hypertension during the long-term follow-up. Antibiotic prophylaxis and antihypertensive treatment were the most employed therapeutic modalities. Seventeen patients progressed to chronic kidney disease (CKD), with thirteen of them eventually reaching end-stage renal disease (ESRD). The time from the initial detection of cysts on an ultrasound (US) to the onset of CKD across the entire cohort was 59.0 (7.0-31124.0) months, whereas the duration from the detection of cysts on an US to the onset of ESRD across the whole cohort was 127.0 (33.0-141.0) months. The median follow-up duration in the cohort was 3.0 (1.0-7.0) years. The patients who progressed to ESRD had clinical symptoms at the time of initial clinical presentation. This study is the first large cohort of patients reported from Croatia. The most common CyKD was the multicystic dysplastic kidney disease. The most common clinical presentation was abdominal distention, abdominal pain, and oliguria. The most common long-term complications were recurrent UTIs, hypertension, CKD, and ESRD.

P023 Serological markers of intestinal barrier function in patients with primary sclerosing cholangitis after liver transplantation

Abstract Background Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease associated with inflammatory bowel disease. Liver transplantation (LT) is the only curative treatment for most patients with PSC. Recurrence of PSC (rPSC) is a common long-term complication after liver transplantation in this patient group, affecting graft survival and overall patient survival. There are several lines of evidence indicating that dysregulation of the microbiome and gut barrier dysfunction are key etiologic factors in the pathogenesis of PSC. The aim of this study was to evaluate serological markers of intestinal barrier function in patients with PSC after LT and in control group, to determine potential biomarkers for rPSC. Methods This is a cross-sectional study of patients after LT for PSC at the Institute for Clinical and Experimental Medicine, Prague. The control group consists of patients who underwent liver transplantation for alcohol-related liver disease and/or hepatocellular carcinoma. The rPSC was assessed by MRCP and/or liver biopsy according to the Mayo criteria. IBD status was assessed by endoscopy, biopsy, and faecal calprotectin. We performed ELISA for Zonulin and Reg3a. The Kruskal-Wallis and Mann-Whitney test were used to evaluate the statistical differences. Results A total of 85 patients were included in the study after LT for PSC and 56 controls. rPSC was detected in 18 (21.18%) patients. IBD was diagnosed in 77 (90.5%) patients, of which 3 (3.9%) were categorised as Crohn’s disease. The remainder, 82 patients, were classified as ulcerative colitis, 41.9% with right-sided predominance and 24.3% with back-wash ileitis. The IBD treatment consisted of 5-ASA in 58 patients, azathioprine in 12 patients, vedolizumab in 5 patients, anti-TNFa in 1 patient and 9 patients were on 10 mg or more of prednisone or equivalent. MayoDAI was evaluated at the time of the visit with mean 1.74 (SD ±2.06). There was a significant difference in Reg3a levels between patients with IBD and control subjects (p<0.05, Figure 1.). No significant difference in Reg3a levels was found between rPSC patients and controls (p=0.3). Interestingly, Zonulin levels were significantly higher in the control group than in PSC patients with or without IBD (p<0.001). No significant difference in Reg3a and Zonulin was found between PSC and rPSC patients and between patients in remission and with active IBD. Conclusion Reg3a was associated with PSC-IBD in patients with PSC after LT, but its association with rPSC is unclear and should be investigated in a prospective setting. Zonulin reached higher levels in the control group.

Independent association of history of diabetic foot with all-cause mortality in patients with type 2 diabetes: the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study

BackgroundFoot ulcers and/or infections are common long-term complications of diabetes and are associated with increased mortality, especially from cardiovascular disease, though only a few studies have investigated the independent contribution of these events to risk of death. This study aimed at assessing the association of history of diabetic foot with all-cause mortality in individuals with type 2 diabetes, independent of cardiovascular risk factors, other complications, and comorbidities.MethodsThis prospective cohort study enrolled 15,773 Caucasian patients in 19 Italian centers in the years 2006–2008. Prior lower extremity, coronary, and cerebrovascular events and major comorbidities were ascertained by medical records, diabetic retinopathy by fundoscopy, diabetic kidney disease by albuminuria and estimated glomerular filtration rate, cardiovascular risk factors by standard methods. All-cause mortality was retrieved for 15,656 patients on 31 October 2015.ResultsAt baseline, 892 patients (5.7%) had a history of diabetic foot, including ulcer/gangrene and/or amputation (n = 565; 3.58%), with (n = 126; 0.80%) or without (n = 439; 2.78%) lower limb revascularization, and revascularization alone (n = 330; 2.09%). History of diabetic foot was associated with all-cause death over a 7.42-year follow-up (adjusted hazard ratio, 1.502 [95% confidence interval, 1.346–1.676], p < 0.0001), independent of confounders, among which age, male sex, smoking, hemoglobin A1c, current treatments, other complications, comorbidities and, inversely, physical activity level and total and HDL cholesterol were correlated independently with mortality. Both ulcer/gangrene and amputation alone were independently associated with death, with a higher strength of association for amputation than for ulcer/gangrene (1.874 [1.144–3.070], p = 0.013 vs. 1.567 [1.353–1.814], p < 0.0001). Both ulcer/gangrene/amputation and lower limb revascularization alone were independently associated with death; mortality risk was much higher for ulcer/gangrene/amputation than for revascularization (1.641 [1.420–1.895], p < 0.0001 vs. 1.229 [1.024–1.475], p = 0.018) and further increased only slightly for combined ulcer/gangrene/amputation and revascularization (1.733 [1.368–2.196], p < 0.0001).ConclusionsIn patients with type 2 diabetes, an history of diabetic foot event, including ulcer/gangrene, amputation, and lower limb revascularization, was associated with a ~ 50% increased risk of subsequent death, independent of cardiovascular risk factors, other complications and severe comorbidities, which were also significantly associated with mortality. The association with mortality was greatest for amputation, whereas that for revascularization alone was relatively modest.Trial registrationClinicalTrials.gov, NCT00715481, retrospectively registered 15 July, 2008.

Treatment of Brachial Plexus Injuries following Gunshot Injuries: A Systematic Review.

Brachial plexus injuries (BPI) from gunshot injuries are uncommon but usually severe and can cause chronic pain, loss of function, and permanent nerve damage. Multiple surgical techniques including neurolysis, end-to-end suture repair, and graft repair have been described for the treatment of these injuries. However, surgical indication, timing, and technique for these injuries remain controversial. This systematic review aims to investigate the treatment modalities for patients with BPI due to gunshot-related injuries. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) methodology was employed for this review. PubMed, Cochrane Reviews, Embase, and CINAHL databases were included. The following keywords constituted our search criteria: gun-shot-wounds, brachial plexus, traum∗, and management. A total of 90 studies were imported for screening, from which 9 papers met our final inclusion/exclusion criteria. The most common studies utilized in this review were retrospective chart reviews followed by case series. In total, there were 628 patients that suffered from gunshot wounds to the brachial plexus. Most patients underwent some form of delayed nerve repair consisting of neurolysis, end-to-end epineural repair, or graft repair with a sural or antebrachial cutaneous nerve graft. Several patients suffered from complications, with neuroma being the most common long-term complication that required reoperation. The optimal timing for surgeries involving BPIs should be determined after examining the level of nerve damage, associated injuries, operative risks, and electrophysiological workup for indications of spontaneous regeneration. Early surgical interventions were indicated for patients presenting with associated vascular or thoracic injuries, compressive masses, and nerve transection by sharp instruments in most selected papers.

Vasculitis-panniculitis mimicking unresolved diabetic foot ulcer.

Diabetes foot ulcer (DFU) is a common long-term complication of diabetes. Intractable chronic wounds to standard care of diabetic foot raise the question of whether other factors intervene in disease development. We report a case of a 54-year-old male patient who came to Sardjito General Hospital with leg pain and previous history of multiple debridement and amputation for DFU referred from a remote hospital yet no improvement was evident in the surrounding lesion following treatment. Consequently, a histopathological examination was carried out proving the presence of other aetiologic factors, vasculitis and panniculitis existing in the lesion. In this case, we report a rare type of causative factor of foot ulcers among diabetic patients. Vasculitis suspected for polyarteritis nodosa accompanied by panniculitis is considered in this patient. The treatment of choice is corticosteroids or immunosuppressants based on the clinical condition, contrary to usual wound care in DFU. Based on the evidence, clinicians need to consider other causes than only macrovascular complications in a diabetic patient with DFU that is intractable to standard wound care. In this patient, vasculitis may be considered in forming diabetic foot ulcers alongside macrovascular complications. A thorough examination is essential to rule out other processes in intractable DFU patients. Prompt management based on proper diagnosis is crucial to prevent peripheral arterial disease complications. Vasculitis and macrovascular complication are inseparable processes forming DFU in this patient.

Prognosis and Factors 4 to 10 Years After Deep Vein Thrombosis: A Long-Term Follow-up Cohort Study.

Post-thrombotic syndrome (PTS) is one of the most common long-term complications of lower extremity deep vein thrombosis (DVT). In order to study the long-term adverse prognosis of patients with DVT, explore the influencing factors for the prognosis of DVT, and provide a reliable reference for future research in the field of venous thrombosis, we collected and summarized information about the incidence of PTS, the PTS score and grading, the associated symptoms and drug-related adverse reactions in 501 patients with DVT. In our study, 54.1% of patients with DVT (271 of 501) experienced indications and manifestations of PTS, the male to female ratio was approximately 1:1. During the long-term follow up, the most common symptoms of PTS were anterior tibial edema and pain. By statistical analysis, we found that the outcome of thrombosis was the influencing factor of PTS score (1-4 points, P<.05). The grading of PTS was primarily influenced by the history of varicose veins and DVT in the lower extremities. The duration of taking antithrombotic drugs affected the outcome of thrombosis (P<.05), especially among the female patients. In addition, varied factors, such as lower extremity DVT complicated with pulmonary embolism and the duration of antithrombotic drug use were found to increase the chances of experiencing drug-related adverse reactions (odds ratio [OR]=2.798, 95% confidence interval [CI]: 1.413-5.541 / OR=2.778, 95% CI: 1.231-6.269). The above 2 factors were significant only among female patients with DVT (OR=4.03, 95% CI: 1.608-10.103 / OR=3.918, 95% CI: 1.123-13.669).

Outcomes of permanent pacemakers and implantable cardioverter-defibrillators in an adult congenital heart disease population

BackgroundBrady- and tachyarrhythmias commonly complicate adult congenital heart disease (ACHD). Permanent pacemakers (PPMs) or implantable cardioverter–defibrillators (ICDs) are often utilised to prevent morbidity or mortality related to arrhythmia, but can also be associated with significant morbidity themselves. MethodsWe analysed outcomes from patients in our comprehensive ACHD database who were seen at least twice since 2000 and once since 2018. Of 1953 ACHD patients, 134 had a PPM and 78 had an ICD (47 for primary and 31 for secondary prevention). ResultsFor PPM patients, 41% had a pacing percentage below 33%, 13% had 33–66%, and 46% had above 66%. One fifth required PPM upgrade, most to cardiac resynchronisation therapy, the rest to ICD. There were 33 appropriate ICD shocks in 15 patients (19%) and 34 inappropriate shocks in 13 patients (17%) over a median follow up of 4.6 years (IQR 0.9–8.3 years). Anti-tachycardia pacing was delivered appropriately for 28% of patients and inappropriately for 9%.Apart from inappropriate therapy, one third of PPM and ICD patients had other device-related complications. Acute PPM complications included lead dysfunction requiring revision (2%), pneumothorax (2%), pleural effusion (2%) and pocket infection (2%). ICDs were also acutely complicated by lead dysfunction (4%) as well as pocket hematoma (3%). The most common long-term complication overall was lead dysfunction, affecting one sixth of both PPM and ICD patients. Finally, the rate of device insertion increased significantly with disease severity. ConclusionsAnti-arrhythmic devices can be lifesaving in ACHD patients, but inappropriate therapy and device-related complications are very common.

Comparison of the Incidence of Nd:YAG Laser Capsulotomy Based on the Type of Intraocular Lens.

Background and Objectives: Posterior capsular opacification (PCO) is the most common long-term complication of successful cataract surgery and can cause visual impairment. We aimed to investigate the effects of intraocular lens (IOL) characteristics on PCO by comparing the incidence of neodymium-doped yttrium aluminum garnet (Nd:YAG) laser capsulotomy for different types of intraocular lenses. Materials and Methods: A retrospective analysis was performed on 2866 eyes that underwent cataract surgery between January 2010 and December 2017, with at least 5 years of follow-up. The IOLs used for surgery were the hydrophobic lenses SN60WF (Alcon, Fort Worth, TX, USA), ZCB00 (Johnson & Johnson Vision, Santa Ana, CA, USA), and MX60 (Bausch & Lomb, Rochester, NY, USA), and the hydrophilic lens MI60 (Bausch & Lomb, Rochester, NY, USA). We analyzed the incidence of Nd:YAG laser capsulotomy according to the type of IOL used. Results: The incidence of Nd:YAG laser capsulotomy was significantly higher with MI60 lenses (31.70%, 175/552 eyes) compared to SN60WF (7.90%, 113/1431 eyes), ZCB00 (10.06%, 64/636 eyes), and MX60 (10.57%, 13/123 eyes; p < 0.001) lenses. The incidence of Nd:YAG laser capsulotomy was significantly lower with the hydrophobic IOLs (8.68%, 190/2190 eyes) than with the hydrophilic IOL (31.70%, 175/552 eyes; p < 0.001). Over time, the rate of increase in the cumulative number of Nd:YAG laser capsulotomy cases was the highest with MI60. The cumulative rate of Nd:YAG laser capsulotomy during the first 3 years was 4.90% with SN60WF (70/1431 eyes), 6.76% with ZCB00 (43/636 eyes), 8.94% with MX60 (11/123 eyes), and 26.10% with MI60 (144/552 eyes) lenses. Conclusions: The incidence of PCO is influenced by the material of the IOLs. The hydrophilic IOL was associated with a higher rate of Nd:YAG laser capsulotomy than the hydrophobic IOLs, with a shorter time to Nd:YAG laser capsulotomy.

Clinical features of acute attacks, chronic symptoms, and long-term complications among patients with acute hepatic porphyria in Japan: a real-world claims database study

BackgroundAcute hepatic porphyria (AHP) is a family of rare genetic diseases, including acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and delta-aminolevulinic acid dehydratase-deficient porphyria. The objective of this retrospective cohort study was to provide information on the clinical features of AHP in Japan—including acute attacks, chronic symptoms, and long-term complications.MethodsPatients with AHP between April 2008 and June 2020 were selected from Japan’s Medical Data Vision claims database. Patients with AHP were matched 1:10, by sex and age, to patients without AHP. The outcomes were evaluated overall, for patients age ≥ 55 years, and for the matched population.ResultsA total of 391 patients with AHP were included from the Japanese Medical Data Vision database. During the observation period (April 2008–June 2020), 18.2% (71/391) of patients experienced 1 acute attack and 10.5% (41/391) experienced ≥ 2 attacks. Chronic symptoms with rates ~ 10% or higher in the AHP population compared with the matched population included neurotic, stress-related, and somatoform disorders (21.7% vs. 6.7% [15.0% difference]); sleep disorders (23.0% vs. 9.9% [13.1% difference]); other and unspecified abdominal pain (13.6% vs. 3.7% [9.9% difference]); and nausea and vomiting, excluding chemotherapy-induced emesis (17.9% vs. 8.1% [9.8% difference]). Long-term complications with higher incidence rates in the AHP population compared with the matched population included fibrosis and cirrhosis of liver (15.9% vs. 3.0% [12.9% difference]), polyneuropathies and other disorders of the peripheral nervous system (20.5% vs. 7.9% [12.6% difference]), liver cancer (16.9% vs. 4.7% [12.2% difference]), renal failure (16.4% vs. 4.3% [12.1% difference]), and hypertension (26.1% vs. 18.8% [7.3% difference]). Among AHP patients age ≥ 55 years, the most common long-term complications were hypertension, kidney failure, and liver cancer.ConclusionsIn Japan, patients with AHP experience a high clinical burden in terms of acute attacks, chronic symptoms, and long-term complications. The clinical burden related to chronic symptoms and long-term complications was substantially higher in Japanese patients with AHP compared with a matched population without AHP. Recognizing these signs and symptoms of AHP may aid physicians in making an earlier diagnosis, which may help patients avoid attack triggers, implement disease management, and reduce lifetime disease burden.