Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

This systematic review of population-based studies of the incidence and early (21 days to 1 month) case fatality of stroke is based on studies published from 1970 to 2008. Stroke incidence (incident strokes only) and case fatality from 21 days to 1 month post-stroke were analysed by four decades of study, two country income groups (high-income countries and low to middle income countries, in accordance with the World Bank's country classification) and, when possible, by stroke pathological type: ischaemic stroke, primary intracerebral haemorrhage, and subarachnoid haemorrhage. This Review shows a divergent, statistically significant trend in stroke incidence rates over the past four decades, with a 42% decrease in stroke incidence in high-income countries and a greater than 100% increase in stroke incidence in low to middle income countries. In 2000-08, the overall stroke incidence rates in low to middle income countries have, for the first time, exceeded the level of stroke incidence seen in high-income countries, by 20%. The time to decide whether or not stroke is an issue that should be on the governmental agenda in low to middle income countries has now passed. Now is the time for action.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(09)70025-0.pdf

Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review

Summary Background Since the early 1980s, imaging techniques have enabled population-based studies of intracerebral haemorrhage. We aimed to assess the incidence, case fatality, and functional outcome of intracerebral haemorrhage in relation to age, sex, ethnic origin, and time period in studies published since 1980. Methods From PubMed and Embase searches with predefined inclusion criteria, we identified population-based studies published between January, 1980, and November, 2008. We calculated incidence and case fatality. Incidences for multiple studies were pooled in a random-effects binomial meta-analysis. Time trends of case fatality were assessed with weighted linear-regression analysis. Findings 36 eligible studies described 44 time periods (mid-year range 1983–2006). These studies included 8145 patients with intracerebral haemorrhage. Incidence did not decrease between 1980 and 2008. Overall incidence was 24·6 per 100 000 person-years (95% CI 19·7–30·7). Incidence was not significantly lower in women than in men (overall incidence ratio 0·85, 95% CI 0·61–1·18). Using the age group 45–54 years as reference, incidence ratios increased from 0·10 (95% CI 0·06–0·14) for people aged less than 45 years to 9·6 (6·6–13·9) for people older than 85 years. Median case fatality at 1 month was 40·4% (range 13·1–61·0) and did not decrease over time, and was lower in Japan (16·7%, 95% CI 15·0–18·5) than elsewhere (42·3%, 40·9–43·6). Six studies reported functional outcome, with independency rates of between 12% and 39%. Incidence of intracerebral haemorrhage per 100 000 person-years was 24·2 (95% CI 20·9–28·0) in white people, 22·9 (14·8–35·6) in black people, 19·6 (15·7–24·5) in Hispanic people, and 51·8 (38·8–69·3) in Asian people. Interpretation Incidence of intracerebral haemorrhage increases with age and has not decreased between 1980 and 2006. Case fatality is lower in Japan than elsewhere, increases with age, and has not decreased over time. More data on functional outcome are needed. Funding Netherlands Heart Foundation.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(09)70340-0.pdf

Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(12)60283-9.pdf

Prediabetes: a high-risk state for diabetes development

Preceding the joint meeting of the 19th annual Diabetic Neuropathy Study Group of the European Association for the Study of Diabetes (NEURODIAB) and the 8th International Symposium on Diabetic Neuropathy in Toronto, Canada, 13-18 October 2009, expert panels were convened to provide updates on classification, definitions, diagnostic criteria, and treatments of diabetic peripheral neuropathies (DPNs), autonomic neuropathy, painful DPNs, and structural alterations in DPNs.

https://care.diabetesjournals.org/content/diacare/33/10/2285.full.pdf

Diabetic Neuropathies: Update on Definitions, Diagnostic Criteria, Estimation of Severity, and Treatments

A fundamental principle in pain medicine is that pain is whatever the patient says the pain is: if there is a large wound but the patient reports no pain then that patient experiences no pain. On the other hand, if the patient reports pain and nothing can be ‘‘seen” by the physician or by a machine, then the patient still has pain but a ready explanation might not be available. The biggest challenge to those trained in classical neurology has been the requirement to provide a proof, with physical evidence, that something is wrong with the patient’s nervous system, though interpretations by physicians may vary. This challenge is particularly difficult when trying to explain symptoms, such as neuropathic pain, which is a symptom arising from injury or diseases of the somatic sensory nervous system, as the recent redefinition for neuropathic pain requires [10]. In fact, the existence of neuropathic pain is a reality only when it is acknowledged by the patient who reports pain and who provides all the critical information about it. The introduction of electrophysiology, including nerve conduction studies, provided information about integrity and pathophysiology of peripheral nerve fiber damage. However, a shortcoming of standard clinical neurophysiology is that it provides information about only 20% of the peripheral nerve fibers and these are large myelinated nerve fibers. The remaining 80% of the fibers are small and are invisible to clinical electrophysiological methods that use standard skin surface electrodes. Epidermal nerve fiber density (ENFD) analysis now provides us with the opportunity to examine the endings of small peripheral nerve fibers in the epidermis. Their quantification has provided important insights into clinical practice and research, ranging from the diagnosis of small fiber neuropathy [2,4] to the study of responses to capsaicin in healthy subjects and in those with neuropathy [7]. However, ENFD provides only histological information. The best approach to gain an insight into the physiology of small nerve fibers is to conduct quantitative sensory testing (QST), which either determines nociceptive mechanical and thermal thresholds or obtains ratings of suprathreshold stimuli. QST has been around for more than a century, but its dependence on a multitude of factors that still need to be better defined was an obstacle to its wider application in clinical and research practice. Factors critical for appropriate application of QST range from the physical properties of the probes and devices that deliver the stimuli to stimulus parameters, such as stimulus duration and inter-stimulus interval, the instruction to patients and their compliance and ability to participate in the study, as well as training and the experience of the persons administering the QST [1]. Recently, these methodological issues concerning QST have been addressed through the development of standardized protocols [8,11]. Though attempts were made to use ENFD to validate QST, and vice versa, the very distinct but complementary nature of these two methodologies needs to be recognized [6]. The complex func-

Taking a peek into pain, from skin to brain with ENFD and QST.

Ophthalmoplegia without ataxia, areflexia or both has been designated as atypical Miller Fisher syndrome (MFS) or acute ophthalmoplegia (AO). This entity, first reported by Chiba et al. is associated with anti-GQ1b IgG antibodies.We report a patient with isolated acute ophthalmoplegia with high titer of anti-GQ1b IgG antibody activity in the acute phase in whom treatment with intravenous immunoglobulin (IVIg) led to the clinical recovery and the decrease in antibody titer.

Acute isolated ophthalmoplegia with anti-GQ1b antibodies.

Skin nerve α-synuclein deposits in a parkinsonian patient with heterozygous parkin mutation.

A case of Bing-Neel syndrome presenting as spinal cord compression.

Objective To assess the prevalence of gastrointestinal symptoms and their correlation with need of non-invasive ventilatory support, intensive care unit admission and death in hospitalized SARS-CoV-2 patients. Design Since February 21th 2020, all individuals referred to our emergency department for suspected SARS-CoV-2 underwent a standardized assessment of body temperature and pulse oximetry, hematological screening, chest X-ray and/or computed tomography (CT), and SARS-CoV-2 assay on nasopharyngeal swab. Medical history and GI symptoms including nausea, vomit, diarrhea, and abdominal pain were recorded. were recorded. Results GI symptoms were the main presentation in 42 (10.2%) of 411 patients, with a mean onset 4.9 +/-… days before admission. In 5 (1.2%) patients GI symptoms have not been associated with respiratory symptoms or fever. We found an inverse trend for ICU admission and death as compared with patients without GI symptoms. Conclusions GI symptoms can be an early and not negligible feature of Covid-19, and might be correlated with a more benign disease course.

/pdf/gastrointestinal-symptoms-as-covid-19-onset-in-hospitalized-dyb66bqqdn.pdf

Giuseppe Lauria

Papers

Taking a peek into pain, from skin to brain with ENFD and QST.

Acute isolated ophthalmoplegia with anti-GQ1b antibodies.

Skin nerve α-synuclein deposits in a parkinsonian patient with heterozygous parkin mutation.

A case of Bing-Neel syndrome presenting as spinal cord compression.

Gastrointestinal symptoms as Covid-19 onset in hospitalized Italian patients