Rejected

Enzyme replacement therapy (ERT) has been shown to stabilize certain aspects of Fabry disease (FD). However, in some patients on ERT, high antibody titres have been documented, with limited clinical improvement in systemic manifestations and often with significant adverse drug reactions. We present two related adolescent males with a 4.5 kb deletion, not amenable to chaperone therapy, leading to profound reduction in α-galactosidase A (α-gal A) enzyme activity. Over a 3-year period of ERT, increasing IgG antibody titres against α-gal A were noted. After starting ERT serial urine globotriaosylceramide (Gb) measurements showed an upward trend from 333 to 2260 μg/mmol creatinine for patient 1 and 1165 to 2260 μg/mmol creatinine for patient 2. Markedly increased levels of urine and plasma globotriaosylsphingosine (Lyso-Gb analogues were also found. The patients experienced recurrent infusion-associated reactions necessitating premedication and prolonged infusion times. Over the 3-year period of ERT, the patients experienced continued malaise, gastrointestinal symptoms and neuropathic pain. In addition, they had increasing anxiety related to their disease and apparent lack of response to ERT which led to a decision to ultimately stop ERT. No other approved treatment options are currently available for these patients. It is possible that the rapid development of the high antidrug neutralizing antibody (ADA) titres is related to the large deletion leading to virtually absent enzyme activity. It remains unclear if their symptomatology during the period of receiving ERT is related to lack of its efficacy, the rising ADA titres, or both. These two patients highlight the need for further research into the management of antidrug antibodies and additional therapeutic approaches for FD.

[This corrects the article on p. 2-24 in vol. 5.].

To study the application of ultrasound-guided indwelling epidural catheter in painless labour.

Discogenic pain is recognized as the most important and most common cause of low back pain (LBP). Intradiscal pulsed radiofrequency (ID-PRF) is used for the treatment of chronic discogenic pain.

Interdisciplinary multimodal pain therapy (IMPT) is based on the biopsychosocial model of pain and describes an integrated treatment for patients with chronic pain. IMPT incorporates a close cooperation of different disciplines, including physicians, psychotherapists, physiotherapists, and others. IMPT mainly aims to restore and increase patients' physical, social and psychological functional capacity. The efficacy of IMPT has been evidenced by systematic reviews and meta-analyses. A number of studies further indicate IMPT's cost-efficiency. Psychotherapy is an essential component of IMPT. Its main goal within the framework of IMPT is to identify and modify dysfunctional patterns of pain coping, and to diagnose and potentially treat psychological comorbidities. Pain psychotherapy comprises mostly cognitive-behavioral interventions which address dysfunctional coping at the three levels of the pain experience (i.e., cognitive, emotional, and behavioral). Research into the efficacy of pain psychotherapy is rather sparse and studies have mostly focused on chronic back pain, yet existing results show promising evidence both for psychotherapy within IMPT and for psychotherapy as a monotherapy. This paper aims at providing an overview of (a) commonly employed cognitive-behavioral psychotherapeutic approaches and strategies in the treatment of chronic pain, and (b) the existing empirical evidence of pain psychotherapy both within the framework of IMPT and as a monotherapy. Future research should include a wider range of pain diagnoses and also investigate the potential benefit of individually-tailored treatments.

Nonunion of a femoral periprosthetic fracture is a rare occurrence in orthopedic practice. Failure of a periprosthetic fracture to heal can lead to substantial disability and pain for patients as well as the potential need for component revision. Relatively little literature exists describing their management and outcome.

Carpal tunnel syndrome (CTS) and vitamin D deficiency are two conditions that cause chronic pain and are thus associated with psychological issues as well. The aim of the present study was to evaluate vitamin D levels, daily calcium intake, musculoskeletal pain and psychological symptoms in patients with CTS. The study included 48 patients with CTS and age-sex matched controls. Serum vitamin D levels were measured, and psychological symptoms were assessed using a Hospital Anxiety and Depression Scale. A Pain DETECT questionnaire was used to assess musculoskeletal pain (MSP) sites and severity. The results showed that vitamin D deficiency was considerably more prevalent in patients with CTS (95.8%) compared with controls (22.9%). Clinical anxiety (35.4 vs. 6.3%) and clinical depression (29.2 vs. 4.2%) were also more common in patients with CTS compared with controls. All the patients with CTS exhibited MSP, whereas none of the controls reported any MSP. Anxiety was significantly and inversely associated with vitamin D levels (r=-0.482; P<0.01), total daily calcium intake (r=-0.294: P<0.05), and positively associated with body mass index (BMI; r=0.200; P≤0.05) and depression (r=0.587; P<0.01). Depression was significantly and inversely associated with vitamin D levels (r=-0.269; P<0.01) and total daily calcium intake (r=-0.236; P<0.05). Logistic regression analysis showed that with every unit increase in serum vitamin D levels, the odds of CTS were decreased 1.22x. While a one-unit increase in anxiety total score was associated with a 14% increase in the odds of having CTS after adjusting for different confounders. In conclusion, vitamin D deficiency, MSP and psychological symptoms are common in patients with CTS. Serum vitamin D levels and anxiety were significant independent predictors of CTS. Based on the results of the present study, it was shown that housewives had an equivalent chance of suffering from CTS morbidity as other high-risk professions. Further studies are required to confirm if vitamin D supplementation could prevent the onset of CTS.

The use of opioid analgesics for pain management in hospitalized patients is associated with a high risk of adverse events, including respiratory depression which may lead to respiratory arrest and death. Patients who experience opioid-related adverse drug reactions (ADRs) have been shown to experience longer and more costly hospital stays and have a higher risk of requiring a readmission after discharge. In this study, we report on the impact of the introduction of Wesley Medical Center's Safe Medication Practice Protocol on opioid-related ADRs.

Nivolumab and pembrolizumab were approved as immune checkpoint inhibitors for third-line treatment of advanced gastric or esophagogastric junction cancer (GC/EGJC) in 2017. However, immunotherapy monotherapy has low efficacy. Apatinib has been proven effective in advanced GC/EGJC. Numerous studies have shown that immunotherapy has a synergistic effect when combined with targeted drug therapy. Based on these facts and to assess the efficacy and safety of programmed death 1 (PD-1) inhibitor and apatinib as combination therapy in patients (pts) with unresectable locally advanced or metastatic GC/EGJC, a retrospective clinical research study was carried out.